Trial Outcomes & Findings for Docetaxel+Oxali+/-Cetux Met Gastric/GEJ (NCT NCT00517829)

Last Updated: 2016-11-28

Results Overview

PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

150 participants

Primary outcome timeframe

Treatment will continue until disease progression or intolerable toxicity, up to 2 years

Results posted on

2016-11-28

Participant Flow

Participant milestones

Participant milestones
Measure	DOCOX Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Overall Study STARTED	75	75
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	75	75

Reasons for withdrawal

Reasons for withdrawal
Measure	DOCOX Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Overall Study Adverse Event	22	34
Overall Study Disease Progression	39	32
Overall Study Patient Request	6	5
Overall Study Investigator Request	5	3
Overall Study Other	3	1

Baseline Characteristics

Docetaxel+Oxali+/-Cetux Met Gastric/GEJ

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DOCOX n=75 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=75 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days	Total n=150 Participants Total of all reporting groups
Age, Continuous	60.5 years STANDARD_DEVIATION 10.9 • n=93 Participants	61.5 years STANDARD_DEVIATION 11.5 • n=4 Participants	61.0 years STANDARD_DEVIATION 11.2 • n=27 Participants
Sex: Female, Male Female	16 Participants n=93 Participants	15 Participants n=4 Participants	31 Participants n=27 Participants
Sex: Female, Male Male	59 Participants n=93 Participants	60 Participants n=4 Participants	119 Participants n=27 Participants
Race/Ethnicity, Customized Caucasian	62 participants n=93 Participants	56 participants n=4 Participants	118 participants n=27 Participants
Race/Ethnicity, Customized Black	5 participants n=93 Participants	7 participants n=4 Participants	12 participants n=27 Participants
Race/Ethnicity, Customized Hispanic	5 participants n=93 Participants	9 participants n=4 Participants	14 participants n=27 Participants
Race/Ethnicity, Customized Asian	3 participants n=93 Participants	1 participants n=4 Participants	4 participants n=27 Participants
Race/Ethnicity, Customized Hawaiian	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized Other	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment United States	75 participants n=93 Participants	75 participants n=4 Participants	150 participants n=27 Participants

PRIMARY outcome

Timeframe: Treatment will continue until disease progression or intolerable toxicity, up to 2 years

Population: ITT population

Outcome measures

Outcome measures
Measure	DOCOX n=75 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=75 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Progression-free Survival	4.7 months Interval 3.0 to 5.6	5.1 months Interval 4.3 to 5.9

SECONDARY outcome

Timeframe: Treatment will continue until disease progression or intolerable toxicity

Population: ITT population

OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.

Outcome measures

Outcome measures
Measure	DOCOX n=75 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=75 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Overall Survival	8.5 months Interval 7.1 to 12.0	9.4 months Interval 6.7 to 10.1

SECONDARY outcome

Timeframe: Treatment will continue until disease progression or intolerable toxicity.

Population: Evaluable Population

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	DOCOX n=68 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=71 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Objective Response Rate (ORR)	26.5 percentage of participants Interval 16.5 to 38.6	38.0 percentage of participants Interval 26.8 to 50.3

SECONDARY outcome

Timeframe: Treatment will continue until disease progression or intolerable toxicity

Population: Patients who achieve a major objective response (CR or PR)

For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response.

Outcome measures

Outcome measures
Measure	DOCOX n=18 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=27 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Time to Response	1.3 months Interval 1.1 to 5.2	1.4 months Interval 1.1 to 4.0

SECONDARY outcome

Timeframe: Treatment will continue until disease progression or intolerable toxicity

Population: Patients who achieve a major objective response (CR or PR).

The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.

Outcome measures

Outcome measures
Measure	DOCOX n=18 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=27 Participants Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Duration of Response	7.3 months Interval 1.5 to 23.7	5.6 months Interval 2.3 to 13.2

Adverse Events

DOCOX

Serious events: 20 serious events

Other events: 65 other events

Deaths: 0 deaths

DOCOX+Cebuximab

Serious events: 26 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Donald Richards

Texas Oncology, Tyler Cancer Center

Phone: 903-579-9800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	DOCOX n=68 participants at risk Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=72 participants at risk Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Gastrointestinal disorders ABDOMINAL PAIN	2.9% 2/68 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Immune system disorders ALLERGIC REACTION	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	2.8% 2/72 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders ANEMIA	4.4% 3/68 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders BRONCHOSPASM	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Investigations CACHEXIA	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Investigations CANCER	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders CHEST PAIN	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders CHILLS	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders CHOLANGITIS	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders COLITIS	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	2.8% 2/72 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders DEFICIENCY VITAMIN	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DEHYDRATION	5.9% 4/68 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	4.2% 3/72 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DIARRHEA	7.4% 5/68 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.6% 4/72 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders EDEMA LARYNX	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Reproductive system and breast disorders EDEMA SCROTAL	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders ESOPHAGEAL DISORDER	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders FATIGUE	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Infections and infestations FEBRILE NEUTROPENIA	10.3% 7/68 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	18.1% 13/72 • Number of events 14 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders FEVER	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Cardiac disorders FIBRILLATION ATRIAL	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders GASTRIC ULCER PERFORATED	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders GASTROINTESTINAL BLEEDING	2.9% 2/68 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders HYPERSENSITIVITY REACTION (NOS)	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPONATREMIA	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOPHOSPHATEMIA	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOXEMIA	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders IMBALANCE BLOOD ELECTROLYTE	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Infections and infestations INFECTION	2.9% 2/68 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Renal and urinary disorders INFECTION BLADDER	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders LEUKOPENIA	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders LUNG FIBROSIS INTERSTITIAL	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Musculoskeletal and connective tissue disorders MUSCLE WEAKNESS	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders NAUSEA	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders NEUROPATHY	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	2.8% 2/72 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders NEUTROPENIA	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	2.8% 2/72 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders PERFORATION GASTROINTESTINAL	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders PNEUMONIA	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Renal and urinary disorders RENAL FAILURE	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Infections and infestations SEPSIS	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders SHOCK	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders STOMATITIS	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders SWEATING	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders SYNCOPE	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders VOMITING	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/72 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders WEAKNESS GENERALIZED	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.4% 1/72 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.

Measure	DOCOX n=68 participants at risk Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days	DOCOX+Cebuximab n=72 participants at risk Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days
Gastrointestinal disorders ABDOMINAL PAIN	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	6.9% 5/72 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Immune system disorders ALLERGIC REACTION	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	8.3% 6/72 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders ALOPECIA	32.4% 22/68 • Number of events 24 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	23.6% 17/72 • Number of events 19 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders ANEMIA	27.9% 19/68 • Number of events 43 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	26.4% 19/72 • Number of events 31 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders ANOREXIA	19.1% 13/68 • Number of events 28 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	16.7% 12/72 • Number of events 16 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders CONSTIPATION	14.7% 10/68 • Number of events 11 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	18.1% 13/72 • Number of events 19 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DEHYDRATION	13.2% 9/68 • Number of events 13 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	15.3% 11/72 • Number of events 20 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DIARRHEA	38.2% 26/68 • Number of events 39 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	47.2% 34/72 • Number of events 92 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders DIZZINESS	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	8.3% 6/72 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders DRY SKIN	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	12.5% 9/72 • Number of events 10 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders FATIGUE	48.5% 33/68 • Number of events 75 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	50.0% 36/72 • Number of events 81 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders FEVER	7.4% 5/68 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	2.8% 2/72 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders FLUSHING	5.9% 4/68 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	2.8% 2/72 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders HEADACHE	5.9% 4/68 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.6% 4/72 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPERGLYCEMIA	2.9% 2/68 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	6.9% 5/72 • Number of events 12 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders HYPERSENSITIVITY REACTION (NOS)	4.4% 3/68 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	12.5% 9/72 • Number of events 12 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOCALCEMIA	1.5% 1/68 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.6% 4/72 • Number of events 10 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOKALEMIA	7.4% 5/68 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	6.9% 5/72 • Number of events 10 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOMAGNESEMIA	5.9% 4/68 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	19.4% 14/72 • Number of events 39 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders INSOMNIA	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.6% 4/72 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders IRRITATION SKIN	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.6% 4/72 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders LEUKOPENIA	19.1% 13/68 • Number of events 26 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	19.4% 14/72 • Number of events 47 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders MUCOSITIS ORAL	4.4% 3/68 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	11.1% 8/72 • Number of events 11 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Musculoskeletal and connective tissue disorders MUSCLE WEAKNESS	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	9.7% 7/72 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders NAUSEA	38.2% 26/68 • Number of events 37 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	37.5% 27/72 • Number of events 53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders NEUROPATHY	25.0% 17/68 • Number of events 23 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	12.5% 9/72 • Number of events 14 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders NEUROPATHY PERIPHERAL	17.6% 12/68 • Number of events 18 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	22.2% 16/72 • Number of events 34 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders NEUTROPENIA	66.2% 45/68 • Number of events 141 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	56.9% 41/72 • Number of events 119 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders PAIN	4.4% 3/68 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	9.7% 7/72 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders PAIN MOUTH	1.5% 1/68 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.6% 4/72 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders RASH	2.9% 2/68 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	23.6% 17/72 • Number of events 36 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders RASH ACNEFORM	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	44.4% 32/72 • Number of events 58 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders STOMATITIS	0.00% 0/68 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	11.1% 8/72 • Number of events 13 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders TASTE ALTERATION	14.7% 10/68 • Number of events 13 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	11.1% 8/72 • Number of events 10 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders THROMBOCYTOPENIA	17.6% 12/68 • Number of events 41 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	11.1% 8/72 • Number of events 23 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders TINGLING	5.9% 4/68 • Number of events 11 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.6% 4/72 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders VOMITING	20.6% 14/68 • Number of events 18 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	16.7% 12/72 • Number of events 20 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders WEAKNESS GENERALIZED	11.8% 8/68 • Number of events 11 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	8.3% 6/72 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.