Trial Outcomes & Findings for Gemcitabine Combinations in Metastatic Breast Cancer (MBC), 1st Line (NCT NCT00191854)

NCT ID: NCT00191854

Last Updated: 2010-03-02

Results Overview

Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

147 participants

Primary outcome timeframe

baseline to measured progressive disease (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death or up to 24 months after randomization)

Results posted on

2010-03-02

Participant Flow

Participant milestones

Participant milestones
Measure	Gemcitabine + Paclitaxel Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Overall Study STARTED	49	47	51
Overall Study Received at Least One Dose of Study Drug	49	47	50
Overall Study COMPLETED	12	17	12
Overall Study NOT COMPLETED	37	30	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Gemcitabine + Paclitaxel Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Overall Study Death	26	23	29
Overall Study Lost to Follow-up	7	5	5
Overall Study Withdrawal by Subject	4	2	3
Overall Study Sponsor Decision	0	0	1
Overall Study Screen Failure	0	0	1

Baseline Characteristics

Gemcitabine Combinations in Metastatic Breast Cancer (MBC), 1st Line

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine + Paclitaxel n=49 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=47 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=51 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles	Total n=147 Participants Total of all reporting groups
Age Continuous	49.8 years STANDARD_DEVIATION 8.8 • n=93 Participants	46.0 years STANDARD_DEVIATION 6.9 • n=4 Participants	49.2 years STANDARD_DEVIATION 10.3 • n=27 Participants	48.4 years STANDARD_DEVIATION 8.9 • n=483 Participants
Sex: Female, Male Female	49 Participants n=93 Participants	47 Participants n=4 Participants	51 Participants n=27 Participants	147 Participants n=483 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment Mexico	1 participants n=93 Participants	2 participants n=4 Participants	3 participants n=27 Participants	6 participants n=483 Participants
Region of Enrollment Brazil	5 participants n=93 Participants	5 participants n=4 Participants	4 participants n=27 Participants	14 participants n=483 Participants
Region of Enrollment Turkey	5 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants	11 participants n=483 Participants
Region of Enrollment China	25 participants n=93 Participants	25 participants n=4 Participants	26 participants n=27 Participants	76 participants n=483 Participants
Region of Enrollment Korea, Republic of	5 participants n=93 Participants	5 participants n=4 Participants	6 participants n=27 Participants	16 participants n=483 Participants
Region of Enrollment India	8 participants n=93 Participants	8 participants n=4 Participants	8 participants n=27 Participants	24 participants n=483 Participants
Eastern Cooperative Oncology Group Performance Status 0 - Fully Active	22 participants n=93 Participants	29 participants n=4 Participants	26 participants n=27 Participants	77 participants n=483 Participants
Eastern Cooperative Oncology Group Performance Status 1 - Ambulatory, Restricted Strenuous Activity	27 participants n=93 Participants	18 participants n=4 Participants	24 participants n=27 Participants	69 participants n=483 Participants
Eastern Cooperative Oncology Group Performance Status Missing Data	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	1 participants n=483 Participants
Menopausal Status Pre-Menopausal	11 participants n=93 Participants	16 participants n=4 Participants	13 participants n=27 Participants	40 participants n=483 Participants
Menopausal Status Peri Menopausal	4 participants n=93 Participants	4 participants n=4 Participants	4 participants n=27 Participants	12 participants n=483 Participants
Menopausal Status Post Menopausal	34 participants n=93 Participants	26 participants n=4 Participants	33 participants n=27 Participants	93 participants n=483 Participants
Menopausal Status Missing Data	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants	2 participants n=483 Participants
Pathological Diagnosis Adenocarcinoma	1 participants n=93 Participants	2 participants n=4 Participants	2 participants n=27 Participants	5 participants n=483 Participants
Pathological Diagnosis Carcinoma, Infiltrating Ductal	42 participants n=93 Participants	40 participants n=4 Participants	45 participants n=27 Participants	127 participants n=483 Participants
Pathological Diagnosis Carcinoma, Infiltrating Lobular	6 participants n=93 Participants	4 participants n=4 Participants	2 participants n=27 Participants	12 participants n=483 Participants
Pathological Diagnosis Carcinoma, Undifferentiated	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Pathological Diagnosis Comedocarcinoma	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	1 participants n=483 Participants
Pathological Diagnosis Missing Data	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	1 participants n=483 Participants
Race/Ethnicity African	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	2 participants n=483 Participants
Race/Ethnicity Caucasian	8 participants n=93 Participants	6 participants n=4 Participants	7 participants n=27 Participants	21 participants n=483 Participants
Race/Ethnicity East Asian	30 participants n=93 Participants	30 participants n=4 Participants	32 participants n=27 Participants	92 participants n=483 Participants
Race/Ethnicity Hispanic	2 participants n=93 Participants	3 participants n=4 Participants	3 participants n=27 Participants	8 participants n=483 Participants
Race/Ethnicity West Asian (West Indian)	8 participants n=93 Participants	8 participants n=4 Participants	8 participants n=27 Participants	24 participants n=483 Participants

PRIMARY outcome

Timeframe: baseline to measured progressive disease (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death or up to 24 months after randomization)

Population: Number of all randomized participants.

Outcome measures

Outcome measures
Measure	Gemcitabine + Paclitaxel n=49 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=47 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=51 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Best Overall Response Complete Response (CR)	1 participants	0 participants	1 participants
Best Overall Response Partial Response (PR)	12 participants	8 participants	7 participants
Best Overall Response Stable Disease (SD)	17 participants	25 participants	29 participants
Best Overall Response Progressive Disease (PD)	14 participants	11 participants	11 participants
Best Overall Response Early Death from Other Causes	1 participants	2 participants	0 participants
Best Overall Response Unknown	4 participants	1 participants	3 participants

SECONDARY outcome

Timeframe: randomization to date of documented disease progression, death on study, start of non-protocol-specified anticancer therapy, or therapy discontinuation due to toxicity, whichever occurred first (up to 6 months)

Population: Number of randomized patients. Censored patients: Gemcitabine + Paclitaxel = 34; Gemcitabine + Carboplatin = 26; Gemcitabine + Cisplatin = 30.

TTTF event was defined as documented disease progression, death on study, start of non-protocol-specified anticancer therapy, or therapy discontinuation due to toxicity. TTTF for patients who were still participating in study without treatment failure at time of analysis were treated as censored at date of last tumor assessment. TTTF for patients who had discontinued from therapy for reasons other than toxicity and who did not experience treatment failure prior to therapy discontinuation were treated as censored on day of study discontinuation.

Outcome measures

Outcome measures
Measure	Gemcitabine + Paclitaxel n=49 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=47 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=51 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Number of Participants With a Time to Treatment Failure (TTTF) Event	15 participants	21 participants	21 participants

SECONDARY outcome

Timeframe: baseline to measured progressive disease or death (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death, or up to 24 months after randomization)

Population: Number of randomized patients. Censored patients: Gemcitabine + Paclitaxel = 20; Gemcitabine + Carboplatin = 18; Gemcitabine + Cisplatin = 28.

PFS was defined as the time from randomizaton to the date of documented disease progression or death on study, whichever occurred first. PFS for participants who discontinued from the study or who had not progressed at the time of analysis were treated as censored at the date of the last tumor assessment.

Outcome measures

Outcome measures
Measure	Gemcitabine + Paclitaxel n=49 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=47 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=51 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Progression Free Survival (PFS)	4.8 months Interval 4.2 to 7.0	4.3 months Interval 3.7 to 5.9	4.8 months Interval 3.7 to 8.1

SECONDARY outcome

Timeframe: time of response to progressive disease or death (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death, or up to 24 months after randomization)

Population: Randomized patients who had either a complete response or partial response. Censored patients: Gemcitabine + Paclitaxel = 4; Gemcitabine + Carboplatin = 4; Gemcitabine + Cisplatin = 14.

Duration of response was measured from time of first documentation of complete response (disappearance of all target lesions) or partial response (30% decrease in sum of longest diameter of target lesions), until date of PFS. Duration of response was censored on day of last tumor assessment for patients who had not progressed or who had discontinued study at time of analysis, and for cases where investigator determined patient had progressive disease and discontinued study therapy and/or started a new, non-protocol-specified anti-cancer therapy before documented disease progression.

Outcome measures

Outcome measures
Measure	Gemcitabine + Paclitaxel n=13 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=8 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=8 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Duration of Response	5.8 months Interval 4.9 to 8.1	3.2 months Interval 1.9 to 5.0	5.1 months Interval 2.9 to 5.1

SECONDARY outcome

Timeframe: baseline to date of death from any cause (up to 34 months)

Population: Number of randomized patients. Censored patients: Gemcitabine + Paclitaxel = 23; Gemcitabine + Carboplatin = 24; Gemcitabine + Cisplatin = 22.

Overall survival time is defined as the time from the date of randomization to date of death due to any cause. Survival time is censored at the date of last contact for patients who are still alive or lost to follow-up.

Outcome measures

Outcome measures
Measure	Gemcitabine + Paclitaxel n=49 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=47 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=51 Participants Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Overall Survival	15.5 months Interval 0.361 to 33.84	22.8 months Interval 1.413 to 26.12	20.1 months Interval 1.413 to 27.83

Adverse Events

Gemcitabine + Paclitaxel

Serious events: 5 serious events

Other events: 48 other events

Deaths: 0 deaths

Gemcitabine + Carboplatin

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Gemcitabine + Cisplatin

Serious events: 0 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Gemcitabine + Paclitaxel n=49 participants at risk Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=47 participants at risk Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=50 participants at risk Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Blood and lymphatic system disorders Anaemia	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Blood and lymphatic system disorders Leukopenia	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Blood and lymphatic system disorders Thrombocytopenia	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
General disorders Pyrexia	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
General disorders Sudden death	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Hepatobiliary disorders Hepatic failure	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Immune system disorders Anaphylactic reaction	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Infections and infestations Cystitis	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Infections and infestations Pneumonia	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Infections and infestations Pyelonephritis	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Infections and infestations Sepsis	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Injury, poisoning and procedural complications Spinal compression fracture	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Haemoglobin decreased	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Renal and urinary disorders Renal failure acute	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/49 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Vascular disorders Hypotension	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.

Other adverse events
Measure	Gemcitabine + Paclitaxel n=49 participants at risk Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles	Gemcitabine + Carboplatin n=47 participants at risk Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles	Gemcitabine + Cisplatin n=50 participants at risk Gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. Cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles
Blood and lymphatic system disorders Anaemia	6.1% 3/49 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	12.8% 6/47 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Blood and lymphatic system disorders Leukopenia	10.2% 5/49 • Number of events 11 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	19.1% 9/47 • Number of events 13 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.0% 5/50 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Blood and lymphatic system disorders Lymphopenia	16.3% 8/49 • Number of events 12 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.3% 2/47 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.0% 4/50 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Blood and lymphatic system disorders Neutropenia	18.4% 9/49 • Number of events 17 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	21.3% 10/47 • Number of events 11 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	12.0% 6/50 • Number of events 8 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Blood and lymphatic system disorders Thrombocytopenia	6.1% 3/49 • Number of events 4 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.6% 5/47 • Number of events 7 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.0% 3/50 • Number of events 7 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Cardiac disorders Palpitations	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.4% 3/47 • Number of events 4 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.0% 2/50 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Abdominal pain	10.2% 5/49 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.3% 2/47 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.0% 4/50 • Number of events 4 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Constipation	14.3% 7/49 • Number of events 11 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	21.3% 10/47 • Number of events 17 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	18.0% 9/50 • Number of events 21 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Diarrhoea	14.3% 7/49 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.6% 5/47 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.0% 5/50 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Dyspepsia	8.2% 4/49 • Number of events 4 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.4% 3/47 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.0% 2/50 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Dysphagia	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.0% 3/50 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Nausea	38.8% 19/49 • Number of events 53 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	53.2% 25/47 • Number of events 61 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	78.0% 39/50 • Number of events 161 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Stomatitis	2.0% 1/49 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.5% 4/47 • Number of events 4 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.0% 3/50 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Gastrointestinal disorders Vomiting	24.5% 12/49 • Number of events 21 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	46.8% 22/47 • Number of events 57 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	62.0% 31/50 • Number of events 127 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
General disorders Asthenia	4.1% 2/49 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.4% 3/47 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	12.0% 6/50 • Number of events 12 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
General disorders Fatigue	36.7% 18/49 • Number of events 32 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	36.2% 17/47 • Number of events 36 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	30.0% 15/50 • Number of events 29 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
General disorders Mucosal inflammation	8.2% 4/49 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.0% 1/50 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
General disorders Oedema	10.2% 5/49 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.4% 3/47 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.0% 2/50 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
General disorders Pyrexia	16.3% 8/49 • Number of events 12 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	17.0% 8/47 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	12.0% 6/50 • Number of events 11 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Infections and infestations Infection	6.1% 3/49 • Number of events 7 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.3% 2/47 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.0% 2/50 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Alanine aminotransferase increased	36.7% 18/49 • Number of events 27 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	42.6% 20/47 • Number of events 22 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	16.0% 8/50 • Number of events 13 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Aspartate aminotransferase increased	28.6% 14/49 • Number of events 20 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	29.8% 14/47 • Number of events 18 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	12.0% 6/50 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Blood alkaline phosphatase increased	8.2% 4/49 • Number of events 4 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.6% 5/47 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.0% 5/50 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Gamma-glutamyltransferase increased	12.2% 6/49 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.5% 4/47 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.0% 2/50 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Haemoglobin decreased	30.6% 15/49 • Number of events 31 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	38.3% 18/47 • Number of events 20 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	36.0% 18/50 • Number of events 27 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Neutrophil count decreased	44.9% 22/49 • Number of events 45 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	29.8% 14/47 • Number of events 28 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	42.0% 21/50 • Number of events 40 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations Platelet count decreased	14.3% 7/49 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	38.3% 18/47 • Number of events 25 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	14.0% 7/50 • Number of events 13 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Investigations White blood cell count decreased	34.7% 17/49 • Number of events 41 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	27.7% 13/47 • Number of events 26 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	26.0% 13/50 • Number of events 28 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Metabolism and nutrition disorders Anorexia	22.4% 11/49 • Number of events 22 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	31.9% 15/47 • Number of events 28 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	16.0% 8/50 • Number of events 18 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Metabolism and nutrition disorders Diabetes mellitus	6.1% 3/49 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.1% 1/47 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.0% 5/50 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Metabolism and nutrition disorders Hypercholesterolaemia	6.1% 3/49 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	4.3% 2/47 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.0% 3/50 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Metabolism and nutrition disorders Hyperglycaemia	4.1% 2/49 • Number of events 2 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.5% 4/47 • Number of events 8 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.0% 3/50 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 7/49 • Number of events 22 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.5% 4/47 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.0% 4/50 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Musculoskeletal and connective tissue disorders Bone pain	4.1% 2/49 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.6% 5/47 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.0% 5/50 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Musculoskeletal and connective tissue disorders Myalgia	30.6% 15/49 • Number of events 46 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.6% 5/47 • Number of events 16 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	14.0% 7/50 • Number of events 22 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	6.1% 3/49 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.4% 3/47 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	2.0% 1/50 • Number of events 1 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Nervous system disorders Headache	12.2% 6/49 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.6% 5/47 • Number of events 8 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	10.0% 5/50 • Number of events 9 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Nervous system disorders Hypoaesthesia	6.1% 3/49 • Number of events 5 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/50 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Nervous system disorders Peripheral sensory neuropathy	22.4% 11/49 • Number of events 16 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.4% 3/47 • Number of events 7 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	8.0% 4/50 • Number of events 6 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.
Psychiatric disorders Anxiety	0.00% 0/49 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	0.00% 0/47 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.	6.0% 3/50 • Number of events 3 Safety analyses were performed on all enrolled patients who received at least one dose of study therapy. All enrolled patients, except for one patient in Gemcitabine + Cisplatin Arm, received at least one dose of study therapy and qualified for safety analyses. The one patient was a screen failure and was discontinued before receiving study drug.