Trial Outcomes & Findings for Docetaxel in Combination With Cisplatin-5-fluorouracil for the Induction Treatment of Nasopharyngeal Carcinoma in Children and Adolescents (NCT NCT00565448)

Last Updated: 2015-07-30

Results Overview

CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the induction treatment and prior to the radiation treatment. CR defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

75 participants

Primary outcome timeframe

after the completion of the induction treatment (up to 9 weeks)

Results posted on

2015-07-30

Participant Flow

Participants were enrolled from November 2007 until October 2008. The study was conducted at 26 centers in 14 countries.

Participant milestones

Participant milestones
Measure	Docetaxel /Cisplatin/5-FU Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.	Cisplatin/5-FU Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.
Overall Study STARTED	50	25
Overall Study COMPLETED	47	23
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Docetaxel /Cisplatin/5-FU Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.	Cisplatin/5-FU Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.
Overall Study Adverse Event	1	2
Overall Study Disease progression	1	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Docetaxel in Combination With Cisplatin-5-fluorouracil for the Induction Treatment of Nasopharyngeal Carcinoma in Children and Adolescents

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Docetaxel /Cisplatin/5-FU n=50 Participants Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.	Cisplatin/5-FU n=25 Participants Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.	Total n=75 Participants Total of all reporting groups
Age, Continuous	16 years n=5 Participants	16 years n=7 Participants	16 years n=5 Participants
Age, Customized Infants from 28 days to 23 months	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized Children from 2 years to <12 years	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Age, Customized Adolescents from 12 years to <16 years	20 participants n=5 Participants	10 participants n=7 Participants	30 participants n=5 Participants
Age, Customized Adolescents >=16	26 participants n=5 Participants	14 participants n=7 Participants	40 participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	6 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	19 Participants n=7 Participants	54 Participants n=5 Participants

PRIMARY outcome

Timeframe: after the completion of the induction treatment (up to 9 weeks)

Population: ITT population: all randomized participants.

Outcome measures

Outcome measures
Measure	Docetaxel /Cisplatin/5-FU n=50 Participants Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy	Cisplatin/5-FU n=25 Participants Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy
Number of Participants With Complete Response (CR)	1 participants	0 participants

SECONDARY outcome

Timeframe: Three plasma samples: one just before then 45 minutes and 5hour after the end of cycle 1 infusion

Population: Participants who were randomized to docetaxel/cisplatin/5-FU and had evaluable docetaxel pharmacokinetic (PK) sample.

AUC estimated by Bayesian method using concentration-time data for each participant and the previously defined adult population model as prior information (with validity of the estimation verified).

Outcome measures

Outcome measures
Measure	Docetaxel /Cisplatin/5-FU n=26 Participants Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy	Cisplatin/5-FU Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy
Docetaxel Area Under the Plasma Concentration-time Curve (AUC) in the Docetaxel/Cisplatin/5-FU Group	3.43 µg*h/mL Standard Deviation 2.05	—

SECONDARY outcome

Timeframe: after the completion of the consolidation treatment (up to 18 weeks)

Population: ITT population: all randomized participants.

OR is classified as CR, partial response (PR), stable disease (SD), progressive disease (PD) or Unknown on completion of both induction and radiation treatment and assessed according to the Modified RECIST from the NCI. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as ≥30% decrease in the sum of the longest diameters (LD) of TLs, taking as reference the disease measurement done at study entry. PD is defined as ≥20% increase in the sum of the LD of TLs, taking as a reference the smallest disease measurement recorded at study entry or the appearance of ≥1 new lesions or unequivocal progression of non-TLs. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Outcome measures

Outcome measures
Measure	Docetaxel /Cisplatin/5-FU n=50 Participants Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy	Cisplatin/5-FU n=25 Participants Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy
Overall Response (OR) CR	1 participants	1 participants
Overall Response (OR) PR	43 participants	20 participants
Overall Response (OR) SD	2 participants	1 participants
Overall Response (OR) PD	2 participants	0 participants
Overall Response (OR) Unknown	0 participants	0 participants
Overall Response (OR) Missing	2 participants	3 participants

SECONDARY outcome

Timeframe: 3 years after the end of the consolidation treatment period (up to 40 months from randomization)

Population: ITT population: all randomized participants.

OS rate is the percentage of participants who survived 3 years after completion of consolidation treatment period. The Kaplan-Meier method was used to estimate OS rate.

Outcome measures

Outcome measures
Measure	Docetaxel /Cisplatin/5-FU n=50 Participants Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy	Cisplatin/5-FU n=25 Participants Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy
Overall Survival (OS) Rate	85.7 percentage of participants Interval 75.9 to 95.5	78.0 percentage of participants Interval 60.8 to 95.1

Adverse Events

Cisplatin/5-FU

Serious events: 11 serious events

Other events: 23 other events

Deaths: 0 deaths

Docetaxel /Cisplatin/5-FU

Serious events: 20 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Cisplatin/5-FU n=25 participants at risk Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.	Docetaxel /Cisplatin/5-FU n=50 participants at risk Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.
Blood and lymphatic system disorders BONE MARROW FAILURE	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders FEBRILE BONE MARROW APLASIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	10.0% 5/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders LEUKOPENIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders NEUTROPENIA/NEUTROPHIL COUNT	8.0% 2/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	8.0% 4/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders THROMBOCYTOPENIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Cardiac disorders TACHYCARDIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders DIARRHOEA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders GASTRITIS	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders MALLORY-WEISS SYNDROME	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders PROCTALGIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders STOMATITIS	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	4.0% 2/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders VOMITING	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	4.0% 2/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
General disorders ASTHENIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
General disorders PYREXIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	4.0% 2/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Immune system disorders HYPERSENSITIVITY	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations CENTRAL LINE INFECTION	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations NEUTROPENIC INFECTION	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations PHARYNGITIS BACTERIAL	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations PNEUMONIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations POSTOPERATIVE WOUND INFECTION	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations SEPTIC SHOCK	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations ALANINE AMINOTRANSFERASE INCREASED	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations BLOOD CREATININE INCREASED	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations HAEMOGLOBIN DECREASED	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders ANOREXIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders DEHYDRATION	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders HYPOCALCAEMIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders HYPOKALAEMIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR HAEMORRHAGE	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Nervous system disorders ATAXIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Nervous system disorders CONVULSION	8.0% 2/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Nervous system disorders HEADACHE	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Renal and urinary disorders ACUTE PRERENAL FAILURE	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Vascular disorders HYPOTENSION	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	2.0% 1/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.

Other adverse events
Measure	Cisplatin/5-FU n=25 participants at risk Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.	Docetaxel /Cisplatin/5-FU n=50 participants at risk Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.
General disorders FATIGUE	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	16.0% 8/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders VOMITING	84.0% 21/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	94.0% 47/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
General disorders ASTHENIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	10.0% 5/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
General disorders MUCOSAL INFLAMMATION	12.0% 3/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	10.0% 5/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders ANAEMIA	12.0% 3/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	28.0% 14/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders BONE MARROW FAILURE	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders LEUKOPENIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	12.0% 6/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders LYMPHOPENIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	12.0% 6/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders NEUTROPENIA/NEUTROPHIL COUNT	28.0% 7/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	40.0% 20/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Ear and labyrinth disorders OTOTOXICITY	24.0% 6/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	14.0% 7/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders ABDOMINAL PAIN	12.0% 3/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	20.0% 10/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	8.0% 2/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	22.0% 11/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders CONSTIPATION	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	14.0% 7/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders DIARRHOEA	12.0% 3/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	30.0% 15/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders DRY MOUTH	20.0% 5/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	18.0% 9/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders DYSPEPSIA	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders DYSPHAGIA	28.0% 7/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	24.0% 12/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders NAUSEA	40.0% 10/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	66.0% 33/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders ODYNOPHAGIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders SALIVARY HYPERSECRETION	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Gastrointestinal disorders STOMATITIS	20.0% 5/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	60.0% 30/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
General disorders PYREXIA	20.0% 5/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	22.0% 11/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Immune system disorders HYPERSENSITIVITY	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	8.0% 4/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations FOLLICULITIS	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	10.0% 5/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations ORAL CANDIDIASIS	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	16.0% 8/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations SINUSITIS	12.0% 3/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	4.0% 2/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	8.0% 2/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Injury, poisoning and procedural complications OVERDOSE	8.0% 2/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	4.0% 2/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Injury, poisoning and procedural complications RADIATION SKIN INJURY	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	22.0% 11/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Injury, poisoning and procedural complications THERMAL BURN	8.0% 2/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	10.0% 5/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations ALANINE AMINOTRANSFERASE INCREASED	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	8.0% 4/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations PLATELET COUNT DECREASED	0.00% 0/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	6.0% 3/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations WEIGHT DECREASED	32.0% 8/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	40.0% 20/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations WEIGHT INCREASED	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	8.0% 4/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Investigations WHITE BLOOD CELL COUNT DECREASED	8.0% 2/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	14.0% 7/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders ANOREXIA	20.0% 5/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	42.0% 21/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders HYPOCALCAEMIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	8.0% 4/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.
Metabolism and nutrition disorders HYPOKALAEMIA	4.0% 1/25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.	12.0% 6/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from first dose up 30 days after administration of the last cycle \[maximum 3 cycle\]). Safety population: all subjects who received at least one cycle of any component of the study drug combination.