Trial Outcomes & Findings for Study Of Irinotecan Hydrochloride (Campto(R)) And Cisplatin Versus Etoposide And Cisplatin In Small Cell Lung Cancer (NCT NCT00143455)
NCT ID: NCT00143455
Last Updated: 2010-02-18
Results Overview
OS was defined as the time from date of randomization to date of death due to any cause. For a subject not expiring, the OS time was censored on the last date of contact that they were known to be alive. The Kaplan-Meier method was used to analyze variables of duration and event associated with possible censoring and estimate the medians survival by treatment groups. The confidence intervals for the medians were calculated using the Brookmeyer and Crowley's method.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
485 participants
Primary outcome timeframe
Baseline to date of death (every 3 weeks for up to 6 months on study treatment and every 2 months for a minimum of 13 months post study treatment)
Results posted on
2010-02-18
Participant Flow
Enrollment of Cohort 1 was terminated early per protocol amendment (29 September 2003). With limited number of subjects in Cohort 1, the efficacy analysis was exploratory. The amendment reduced Irinotecan dose from 80 to 65 mg/m2. With the study powered for Overall Survival in subjects recruited thereafter (Cohort 2) efficacy analysis is reported.
Participant milestones
| Measure |
Irinotecan + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Cohort 1
STARTED
|
39
|
39
|
0
|
0
|
|
Cohort 1
Received Treatment
|
39
|
38
|
0
|
0
|
|
Cohort 1
COMPLETED
|
25
|
22
|
0
|
0
|
|
Cohort 1
NOT COMPLETED
|
14
|
17
|
0
|
0
|
|
Cohort 2
STARTED
|
0
|
0
|
203
|
204
|
|
Cohort 2
Received Treatment
|
0
|
0
|
202
|
203
|
|
Cohort 2
COMPLETED
|
0
|
0
|
97
|
111
|
|
Cohort 2
NOT COMPLETED
|
0
|
0
|
106
|
93
|
Reasons for withdrawal
| Measure |
Irinotecan + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Cohort 1
Adverse Event
|
8
|
4
|
0
|
0
|
|
Cohort 1
Death
|
5
|
2
|
0
|
0
|
|
Cohort 1
Progressive Disease
|
0
|
6
|
0
|
0
|
|
Cohort 1
Withdrawal by Subject
|
1
|
4
|
0
|
0
|
|
Cohort 1
Randomized But Not Treated
|
0
|
1
|
0
|
0
|
|
Cohort 2
Adverse Event
|
0
|
0
|
42
|
30
|
|
Cohort 2
No Longer Required Study Treatment
|
0
|
0
|
1
|
0
|
|
Cohort 2
Protocol Violation
|
0
|
0
|
1
|
1
|
|
Cohort 2
Lost to Follow-up
|
0
|
0
|
1
|
4
|
|
Cohort 2
Death
|
0
|
0
|
20
|
12
|
|
Cohort 2
Progressive Disease
|
0
|
0
|
20
|
27
|
|
Cohort 2
Withdrawal by Subject
|
0
|
0
|
13
|
12
|
|
Cohort 2
Other
|
0
|
0
|
7
|
6
|
|
Cohort 2
Randomized But Not Treated
|
0
|
0
|
1
|
1
|
Baseline Characteristics
Study Of Irinotecan Hydrochloride (Campto(R)) And Cisplatin Versus Etoposide And Cisplatin In Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Irinotecan + Cisplatin (Cohort 1)
n=39 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
n=38 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
n=202 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
n=203 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Total
n=482 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
18 to 44 years
|
2 participants
n=93 Participants
|
1 participants
n=4 Participants
|
11 participants
n=27 Participants
|
6 participants
n=483 Participants
|
20 participants
n=36 Participants
|
|
Age, Customized
45 to 64 years
|
27 participants
n=93 Participants
|
24 participants
n=4 Participants
|
134 participants
n=27 Participants
|
130 participants
n=483 Participants
|
315 participants
n=36 Participants
|
|
Age, Customized
> = 65 years
|
10 participants
n=93 Participants
|
13 participants
n=4 Participants
|
57 participants
n=27 Participants
|
67 participants
n=483 Participants
|
147 participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
48 Participants
n=27 Participants
|
48 Participants
n=483 Participants
|
110 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
154 Participants
n=27 Participants
|
155 Participants
n=483 Participants
|
372 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Baseline to date of death (every 3 weeks for up to 6 months on study treatment and every 2 months for a minimum of 13 months post study treatment)Population: FAP = Full analysis population (all treated patients)analyzed in the arm they were assigned by randomization, assuming they had a confirmed small cell lung cancer. The enrollment of Cohort 1 was terminated early per protocol amendment (29 September 2003). With limited number of subjects in Cohort 1, the efficacy analysis was exploratory.
OS was defined as the time from date of randomization to date of death due to any cause. For a subject not expiring, the OS time was censored on the last date of contact that they were known to be alive. The Kaplan-Meier method was used to analyze variables of duration and event associated with possible censoring and estimate the medians survival by treatment groups. The confidence intervals for the medians were calculated using the Brookmeyer and Crowley's method.
Outcome measures
| Measure |
Irinotecan + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
n=202 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
n=203 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Overall Survival (OS) for the Full Analysis Population (FAP)
|
—
|
—
|
10.2177 months
Interval 8.9692 to 11.6632
|
9.6591 months
Interval 8.9363 to 11.0719
|
PRIMARY outcome
Timeframe: Baseline to date of death (every 3 weeks for up to 6 months on study treatment and every 2 months for a minimum of 13 months post study treatment)Population: PP population = a subset of the Cohort 2 FAP. The subjects had to be eligible (subject had no major protocol deviations from inclusion and noninclusion criteria), evaluable for response, without any major protocol deviations during the study.
OS was defined as the time from date of randomization to date of death due to any cause. For a subject not expiring, the OS time was censored on the last date of contact that they were known to be alive. The Kaplan-Meier method was used to analyze variables of duration and event associated with possible censoring and estimate the medians survival by treatment groups. The confidence intervals for the medians were calculated using the Brookmeyer and Crowley's method.
Outcome measures
| Measure |
Irinotecan + Cisplatin (Cohort 1)
n=176 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
n=186 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Overall Survival for the Per Protocol (PP) Population
|
10.5791 months
Interval 9.2977 to 12.2875
|
9.4292 months
Interval 8.5092 to 10.1848
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to first documentation of confirmed response (every 9 weeks for up to 6 months on study treatment and every 2 months in follow up until progression)Population: FAP = Full analysis population (all treated patients)analyzed in the arm they were assigned by randomization, assuming they had a confirmed small cell lung cancer. The enrollment of Cohort 1 was terminated early per protocol amendment (29 September 2003). With limited number of subjects in Cohort 1, the efficacy analysis was exploratory.
Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Outcome measures
| Measure |
Irinotecan + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
n=202 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
n=203 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Number of Subjects With Overall Confirmed Response
|
—
|
—
|
79 participants
|
94 participants
|
SECONDARY outcome
Timeframe: Baseline to first documentation of confirmed response (every 9 weeks for up to 6 months on study treatment and every 2 months in follow up until progression)Population: FAP = Full analysis population (all treated patients) of Cohort 2 (after the 29 September 2003 protocol amendment), analyzed in the arm they were assigned by randomization, assuming they had a confirmed small cell lung cancer.
DR was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression. The Kaplan-Meier method was used to analyze variables of duration and event associated with possible censoring and estimate the medians survival by treatment groups. The confidence intervals for the medians were calculated using the Brookmeyer and Crowley's method.
Outcome measures
| Measure |
Irinotecan + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
n=202 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
n=203 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Duration of Response (DR)
|
—
|
—
|
5.5195 months
Interval 4.8953 to 6.1437
|
4.8953 months
Interval 4.8296 to 5.2895
|
SECONDARY outcome
Timeframe: Baseline to date of progression (every 9 weeks for up to 6 months on study treatment and every 2 months for a minimum of 13 months post study treatment until progression)Population: FAP = Full analysis population (all treated patients)analyzed in the arm they were assigned by randomization, assuming they had a confirmed small cell lung cancer. The enrollment of Cohort 1 was terminated early per protocol amendment (29 September 2003). With limited number of subjects in Cohort 1, the efficacy analysis was exploratory.
TTP was defined as the time from date of randomization to the date of the first documentation of tumor progression. The Kaplan-Meier method was used to analyze variables of duration and event associated with possible censoring and estimate the medians survival by treatment groups. The confidence intervals for the medians were calculated using the Brookmeyer and Crowley's method.
Outcome measures
| Measure |
Irinotecan + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
n=202 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
n=203 Participants
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Time to Tumor Progression (TTP)
|
—
|
—
|
5.3552 months
Interval 4.9281 to 6.2423
|
6.2423 months
Interval 5.6838 to 6.7023
|
SECONDARY outcome
Timeframe: Baseline, at every cycle (Day -1, Day 1 of cycle before treatment), at the end of the treatment, and every 2 months during follow-upPopulation: Data were not analyzed.
The EORTC QLQ-C30 scales include 5 functional scales (physical, role, cognitive, emotional, and social), a global health status/QL scale and 9 symptom scales: nausea and vomiting, pain, fatigue, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties. All scales and single-item measures range from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, for the global health status/QL represents a high QL (better patient state), and for a symptom scale/item represents a high level of symptomatology/problems (worse patient state).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Every 3 weeks for up to 6 months on study treatmentPopulation: Data were not analyzed.
Improvement of ≥ 1 tumor related symptom = clinical benefit responder. Pain improvement = decrease of ≥ 1 National Cancer Institute (NCI) grade from baseline of ≥ 1 symptom of NCI pain category, without pain symptom worsening. Cough, dyspnea and hemoptysis improvement = decrease of ≥ 1 NCI grade from baseline. Positive weight change ≥ 5 percent gain from baseline. Positive analgesic consumption = change from baseline from opioid to non-opioid category.
Outcome measures
Outcome data not reported
Adverse Events
Irinotecan + Cisplatin (Cohort 1)
Serious events: 9 serious events
Other events: 39 other events
Deaths: 0 deaths
Etoposide + Cisplatin (Cohort 1)
Serious events: 4 serious events
Other events: 38 other events
Deaths: 0 deaths
Irinotecan + Cisplatin (Cohort 2)
Serious events: 45 serious events
Other events: 202 other events
Deaths: 0 deaths
Etoposide + Cisplatin (Cohort 2)
Serious events: 29 serious events
Other events: 203 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Irinotecan + Cisplatin (Cohort 1)
n=39 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
n=38 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
n=202 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
n=203 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/39
|
0.00%
0/38
|
2.0%
4/202
|
3.0%
6/203
|
|
Blood and lymphatic system disorders
Hand and foot syndrome secondary to sickle cell anaemia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Blood and lymphatic system disorders
Leukopenia NOS
|
7.7%
3/39
|
2.6%
1/38
|
5.0%
10/202
|
2.5%
5/203
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Blood and lymphatic system disorders
Lymphatic disorder
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.1%
2/39
|
2.6%
1/38
|
6.4%
13/202
|
5.9%
12/203
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.6%
1/39
|
2.6%
1/38
|
3.0%
6/202
|
2.0%
4/203
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Cardiac disorders
Cardiac disorder NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Cardiac disorders
Cardiac tamponade
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Cardiac disorders
Cardiovascular disorder NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Cardiac disorders
Left ventricular failure
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/39
|
2.6%
1/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/39
|
0.00%
0/38
|
0.99%
2/202
|
0.49%
1/203
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.99%
2/203
|
|
Cardiac disorders
Supraventricular arrhythmia NOS
|
0.00%
0/39
|
2.6%
1/38
|
1.5%
3/202
|
0.99%
2/203
|
|
Cardiac disorders
Tachycardia NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Cardiac disorders
Ventricular arrhythmia NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Ear and labyrinth disorders
Conductive deafness
|
2.6%
1/39
|
2.6%
1/38
|
0.50%
1/202
|
0.99%
2/203
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Ear and labyrinth disorders
Vertigo
|
2.6%
1/39
|
0.00%
0/38
|
0.99%
2/202
|
0.49%
1/203
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Eye disorders
Dry eye NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Eye disorders
Ocular icterus
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Eye disorders
Vision blurred
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Eye disorders
Visual disturbance NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Abdominal pain NOS
|
2.6%
1/39
|
5.3%
2/38
|
3.0%
6/202
|
1.5%
3/203
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Gastrointestinal disorders
Colitis NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.99%
2/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/39
|
0.00%
0/38
|
3.5%
7/202
|
3.0%
6/203
|
|
Gastrointestinal disorders
Diarrhoea NOS
|
12.8%
5/39
|
2.6%
1/38
|
16.3%
33/202
|
2.5%
5/203
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/39
|
0.00%
0/38
|
0.99%
2/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/39
|
0.00%
0/38
|
0.99%
2/202
|
0.99%
2/203
|
|
Gastrointestinal disorders
Epigastric discomfort
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Ileus paralytic
|
2.6%
1/39
|
0.00%
0/38
|
1.5%
3/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Intestinal obstruction NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Gastrointestinal disorders
Nausea
|
15.4%
6/39
|
5.3%
2/38
|
11.4%
23/202
|
5.9%
12/203
|
|
Gastrointestinal disorders
Proctitis NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Gastrointestinal disorders
Rectal tenesmus
|
2.6%
1/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/39
|
0.00%
0/38
|
1.5%
3/202
|
0.49%
1/203
|
|
Gastrointestinal disorders
Vomiting NOS
|
12.8%
5/39
|
5.3%
2/38
|
10.9%
22/202
|
3.4%
7/203
|
|
General disorders
Chest pain
|
5.1%
2/39
|
2.6%
1/38
|
5.4%
11/202
|
3.0%
6/203
|
|
General disorders
Fatigue
|
17.9%
7/39
|
10.5%
4/38
|
12.4%
25/202
|
6.9%
14/203
|
|
General disorders
General physical health deterioration
|
0.00%
0/39
|
0.00%
0/38
|
6.9%
14/202
|
4.4%
9/203
|
|
General disorders
Injection site reaction NOS
|
0.00%
0/39
|
2.6%
1/38
|
0.00%
0/202
|
0.49%
1/203
|
|
General disorders
Multi-organ failure
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
General disorders
Oedema NOS
|
2.6%
1/39
|
2.6%
1/38
|
3.5%
7/202
|
2.0%
4/203
|
|
General disorders
Oedema peripheral
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
General disorders
Pain NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
General disorders
Pyrexia
|
5.1%
2/39
|
0.00%
0/38
|
5.0%
10/202
|
2.5%
5/203
|
|
General disorders
Sudden death
|
0.00%
0/39
|
0.00%
0/38
|
0.99%
2/202
|
0.00%
0/203
|
|
Hepatobiliary disorders
Hepatic pain
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Infections and infestations
Encephalitis herpes
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Infections and infestations
Infection NOS
|
5.1%
2/39
|
2.6%
1/38
|
4.5%
9/202
|
3.0%
6/203
|
|
Infections and infestations
Lung infection NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Infections and infestations
Pneumonia NOS
|
0.00%
0/39
|
0.00%
0/38
|
1.5%
3/202
|
0.49%
1/203
|
|
Infections and infestations
Respiratory tract infection NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Infections and infestations
Skin fungal infection NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Infections and infestations
Urinary tract infection NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Investigations
Alanine aminotransferase increased
|
2.6%
1/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Investigations
Aspartate aminotransferase increased
|
2.6%
1/39
|
0.00%
0/38
|
0.50%
1/202
|
0.99%
2/203
|
|
Investigations
Blood alkaline phosphatase NOS increased
|
2.6%
1/39
|
0.00%
0/38
|
0.00%
0/202
|
0.99%
2/203
|
|
Investigations
Blood bilirubin increased
|
2.6%
1/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Investigations
Blood creatine increased
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Investigations
Blood creatinine increased
|
0.00%
0/39
|
2.6%
1/38
|
2.5%
5/202
|
1.5%
3/203
|
|
Investigations
Blood urea increased
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Investigations
Haemoglobin decreased
|
5.1%
2/39
|
2.6%
1/38
|
4.5%
9/202
|
2.5%
5/203
|
|
Investigations
Weight decreased
|
15.4%
6/39
|
0.00%
0/38
|
9.9%
20/202
|
4.9%
10/203
|
|
Metabolism and nutrition disorders
Alkalosis NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Metabolism and nutrition disorders
Anorexia
|
5.1%
2/39
|
0.00%
0/38
|
5.9%
12/202
|
4.9%
10/203
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Metabolism and nutrition disorders
Dehydration
|
5.1%
2/39
|
2.6%
1/38
|
2.5%
5/202
|
0.00%
0/203
|
|
Metabolism and nutrition disorders
General nutrition disorder
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.6%
1/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.99%
2/203
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.1%
2/39
|
0.00%
0/38
|
3.0%
6/202
|
0.99%
2/203
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.99%
2/203
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.7%
3/39
|
2.6%
1/38
|
3.5%
7/202
|
3.9%
8/203
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.1%
2/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Musculoskeletal and connective tissue disorders
Pain in limb
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
5.1%
2/39
|
5.3%
2/38
|
0.99%
2/202
|
1.5%
3/203
|
|
Nervous system disorders
Ataxia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Nervous system disorders
Cerebral ischaemia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Nervous system disorders
Cholinergic syndrome
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.99%
2/203
|
|
Nervous system disorders
Dizziness
|
2.6%
1/39
|
2.6%
1/38
|
0.99%
2/202
|
0.99%
2/203
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Nervous system disorders
Dysphonia
|
2.6%
1/39
|
2.6%
1/38
|
2.5%
5/202
|
2.5%
5/203
|
|
Nervous system disorders
Epilepsy NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Nervous system disorders
Extrapyramidal disorder
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Nervous system disorders
Facial palsy
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Nervous system disorders
Headache
|
2.6%
1/39
|
0.00%
0/38
|
3.5%
7/202
|
2.5%
5/203
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Nervous system disorders
Nystagmus NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Nervous system disorders
Paraesthesia
|
5.1%
2/39
|
2.6%
1/38
|
1.5%
3/202
|
1.5%
3/203
|
|
Nervous system disorders
Paralysis NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Nervous system disorders
Peripheral motor neuropathy
|
2.6%
1/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Nervous system disorders
Sciatica
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/39
|
0.00%
0/38
|
1.5%
3/202
|
0.00%
0/203
|
|
Nervous system disorders
Syncope
|
0.00%
0/39
|
2.6%
1/38
|
2.0%
4/202
|
0.00%
0/203
|
|
Nervous system disorders
Tremor
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Psychiatric disorders
Anxiety
|
2.6%
1/39
|
0.00%
0/38
|
0.99%
2/202
|
0.49%
1/203
|
|
Psychiatric disorders
Bradyphrenia
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Psychiatric disorders
Confusional state
|
2.6%
1/39
|
0.00%
0/38
|
4.0%
8/202
|
0.49%
1/203
|
|
Psychiatric disorders
Depression
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
2.0%
4/203
|
|
Psychiatric disorders
Insomnia
|
5.1%
2/39
|
0.00%
0/38
|
3.5%
7/202
|
0.49%
1/203
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/39
|
2.6%
1/38
|
0.00%
0/202
|
0.99%
2/203
|
|
Renal and urinary disorders
Haemorrhage urinary tract
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Renal and urinary disorders
Incontinence NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Renal and urinary disorders
Renal failure NOS
|
0.00%
0/39
|
0.00%
0/38
|
2.0%
4/202
|
1.5%
3/203
|
|
Renal and urinary disorders
Urinary frequency
|
0.00%
0/39
|
0.00%
0/38
|
0.99%
2/202
|
0.00%
0/203
|
|
Renal and urinary disorders
Urinary retention
|
2.6%
1/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.3%
4/39
|
5.3%
2/38
|
12.4%
25/202
|
7.4%
15/203
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea NOS
|
12.8%
5/39
|
5.3%
2/38
|
14.9%
30/202
|
10.8%
22/203
|
|
Respiratory, thoracic and mediastinal disorders
Expectoration
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.6%
1/39
|
2.6%
1/38
|
2.0%
4/202
|
2.0%
4/203
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnoea
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.1%
2/39
|
2.6%
1/38
|
2.0%
4/202
|
1.5%
3/203
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/39
|
2.6%
1/38
|
4.5%
9/202
|
3.0%
6/203
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Skin and subcutaneous tissue disorders
Exanthem
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Skin and subcutaneous tissue disorders
Rash NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Skin and subcutaneous tissue disorders
Skin striae
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Skin and subcutaneous tissue disorders
Sweating increased
|
2.6%
1/39
|
0.00%
0/38
|
0.99%
2/202
|
3.0%
6/203
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Vascular disorders
Deep vein thrombosis
|
2.6%
1/39
|
2.6%
1/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Vascular disorders
Haematoma NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.00%
0/203
|
|
Vascular disorders
Hypertension NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.99%
2/203
|
|
Vascular disorders
Hypotension NOS
|
5.1%
2/39
|
0.00%
0/38
|
0.99%
2/202
|
0.99%
2/203
|
|
Vascular disorders
Petechiae
|
0.00%
0/39
|
0.00%
0/38
|
0.99%
2/202
|
0.00%
0/203
|
|
Vascular disorders
Phlebitis NOS
|
0.00%
0/39
|
0.00%
0/38
|
0.00%
0/202
|
0.49%
1/203
|
|
Vascular disorders
Superior vena caval occlusion
|
0.00%
0/39
|
0.00%
0/38
|
0.50%
1/202
|
0.49%
1/203
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/39
|
2.6%
1/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Metabolism and nutrition disorders
Hyperglycaemia NOS
|
5.1%
2/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour lysis syndrome
|
2.6%
1/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Nervous system disorders
Convulsions NOS
|
2.6%
1/39
|
2.6%
1/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
2.6%
1/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Vascular disorders
Haemorrhage NOS
|
2.6%
1/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Vascular disorders
Phlebitis superficial
|
0.00%
0/39
|
2.6%
1/38
|
0.00%
0/202
|
0.00%
0/203
|
Other adverse events
| Measure |
Irinotecan + Cisplatin (Cohort 1)
n=39 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 80 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 1)
n=38 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Irinotecan + Cisplatin (Cohort 2)
n=202 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of : Irinotecan hydrochloride 65 mg/m2 administered intravenously (IV) over 30 - 90 minutes on Day 1 and Day 8 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
Etoposide + Cisplatin (Cohort 2)
n=203 participants at risk
Each chemotherapy cycle was repeated every 21 days (3 weeks) and consisted of: Etoposide 100 mg/m2 administered intravenously (IV) on Day 1, Day 2 and Day 3 followed by cisplatin 80 mg/m2 administered intravenously (IV) over 30-60 minutes on Day 1.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia NOS
|
7.7%
3/39
|
2.6%
1/38
|
10.4%
21/202
|
16.7%
34/203
|
|
Blood and lymphatic system disorders
Neutropenia
|
46.2%
18/39
|
47.4%
18/38
|
53.0%
107/202
|
64.5%
131/203
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
15.4%
6/39
|
10.5%
4/38
|
12.9%
26/202
|
16.7%
34/203
|
|
Ear and labyrinth disorders
Conductive deafness
|
2.6%
1/39
|
13.2%
5/38
|
7.9%
16/202
|
9.4%
19/203
|
|
Ear and labyrinth disorders
Vertigo
|
7.7%
3/39
|
0.00%
0/38
|
8.4%
17/202
|
6.4%
13/203
|
|
Gastrointestinal disorders
Abdominal pain NOS
|
10.3%
4/39
|
13.2%
5/38
|
13.4%
27/202
|
10.3%
21/203
|
|
Gastrointestinal disorders
Constipation
|
7.7%
3/39
|
21.1%
8/38
|
20.3%
41/202
|
25.6%
52/203
|
|
Gastrointestinal disorders
Diarrhoea NOS
|
43.6%
17/39
|
10.5%
4/38
|
55.9%
113/202
|
13.8%
28/203
|
|
Gastrointestinal disorders
Dyspepsia
|
2.6%
1/39
|
5.3%
2/38
|
8.4%
17/202
|
8.4%
17/203
|
|
Gastrointestinal disorders
Dysphagia
|
7.7%
3/39
|
2.6%
1/38
|
4.5%
9/202
|
5.4%
11/203
|
|
Gastrointestinal disorders
Nausea
|
59.0%
23/39
|
57.9%
22/38
|
66.8%
135/202
|
60.6%
123/203
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/39
|
18.4%
7/38
|
10.4%
21/202
|
11.3%
23/203
|
|
Gastrointestinal disorders
Vomiting NOS
|
46.2%
18/39
|
47.4%
18/38
|
55.4%
112/202
|
41.4%
84/203
|
|
General disorders
Chest pain
|
30.8%
12/39
|
31.6%
12/38
|
32.7%
66/202
|
25.1%
51/203
|
|
General disorders
Fatigue
|
71.8%
28/39
|
71.1%
27/38
|
64.9%
131/202
|
60.6%
123/203
|
|
General disorders
General physical health deterioration
|
0.00%
0/39
|
0.00%
0/38
|
5.4%
11/202
|
3.0%
6/203
|
|
General disorders
Oedema NOS
|
5.1%
2/39
|
10.5%
4/38
|
14.4%
29/202
|
12.3%
25/203
|
|
General disorders
Pyrexia
|
15.4%
6/39
|
0.00%
0/38
|
11.9%
24/202
|
10.3%
21/203
|
|
Infections and infestations
Infection NOS
|
2.6%
1/39
|
15.8%
6/38
|
12.4%
25/202
|
15.8%
32/203
|
|
Investigations
Blood creatinine increased
|
10.3%
4/39
|
10.5%
4/38
|
15.8%
32/202
|
14.8%
30/203
|
|
Investigations
Haemoglobin decreased
|
17.9%
7/39
|
10.5%
4/38
|
23.8%
48/202
|
24.6%
50/203
|
|
Investigations
Weight decreased
|
51.3%
20/39
|
31.6%
12/38
|
41.1%
83/202
|
30.0%
61/203
|
|
Metabolism and nutrition disorders
Anorexia
|
41.0%
16/39
|
28.9%
11/38
|
40.1%
81/202
|
32.5%
66/203
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/39
|
7.9%
3/38
|
6.4%
13/202
|
2.0%
4/203
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/39
|
0.00%
0/38
|
6.4%
13/202
|
5.9%
12/203
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.1%
2/39
|
5.3%
2/38
|
4.0%
8/202
|
5.4%
11/203
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/39
|
0.00%
0/38
|
5.4%
11/202
|
5.9%
12/203
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
28.2%
11/39
|
26.3%
10/38
|
22.8%
46/202
|
23.2%
47/203
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
25.6%
10/39
|
26.3%
10/38
|
8.4%
17/202
|
5.4%
11/203
|
|
Nervous system disorders
Cholinergic syndrome
|
5.1%
2/39
|
0.00%
0/38
|
5.0%
10/202
|
0.00%
0/203
|
|
Nervous system disorders
Dizziness
|
5.1%
2/39
|
2.6%
1/38
|
5.9%
12/202
|
5.9%
12/203
|
|
Nervous system disorders
Dysgeusia
|
7.7%
3/39
|
0.00%
0/38
|
6.4%
13/202
|
3.9%
8/203
|
|
Nervous system disorders
Dysphonia
|
10.3%
4/39
|
10.5%
4/38
|
13.9%
28/202
|
15.8%
32/203
|
|
Nervous system disorders
Headache
|
7.7%
3/39
|
13.2%
5/38
|
17.3%
35/202
|
16.7%
34/203
|
|
Nervous system disorders
Paraesthesia
|
20.5%
8/39
|
23.7%
9/38
|
26.7%
54/202
|
24.6%
50/203
|
|
Nervous system disorders
Peripheral motor neuropathy
|
2.6%
1/39
|
10.5%
4/38
|
3.5%
7/202
|
6.4%
13/203
|
|
Psychiatric disorders
Anxiety
|
2.6%
1/39
|
7.9%
3/38
|
5.0%
10/202
|
4.9%
10/203
|
|
Psychiatric disorders
Depression
|
0.00%
0/39
|
5.3%
2/38
|
5.9%
12/202
|
3.9%
8/203
|
|
Psychiatric disorders
Insomnia
|
17.9%
7/39
|
10.5%
4/38
|
13.4%
27/202
|
15.3%
31/203
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
61.5%
24/39
|
60.5%
23/38
|
64.4%
130/202
|
64.0%
130/203
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea NOS
|
53.8%
21/39
|
57.9%
22/38
|
66.3%
134/202
|
68.5%
139/203
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/39
|
0.00%
0/38
|
5.9%
12/202
|
3.0%
6/203
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
7.7%
3/39
|
7.9%
3/38
|
10.4%
21/202
|
14.3%
29/203
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
15.4%
6/39
|
21.1%
8/38
|
7.9%
16/202
|
8.9%
18/203
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
35.9%
14/39
|
57.9%
22/38
|
38.6%
78/202
|
50.7%
103/203
|
|
Skin and subcutaneous tissue disorders
Sweating increased
|
0.00%
0/39
|
0.00%
0/38
|
7.4%
15/202
|
9.9%
20/203
|
|
Vascular disorders
Hypertension NOS
|
0.00%
0/39
|
0.00%
0/38
|
4.0%
8/202
|
5.4%
11/203
|
|
Cardiac disorders
Sinus tachycardia
|
5.1%
2/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Cardiac disorders
Supraventricular arrhythmia NOS
|
5.1%
2/39
|
2.6%
1/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Cardiac disorders
Ventricular arrhythmia NOS
|
5.1%
2/39
|
2.6%
1/38
|
0.00%
0/202
|
0.00%
0/203
|
|
General disorders
Injection site reaction NOS
|
2.6%
1/39
|
5.3%
2/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Hepatobiliary disorders
Hepatomegaly
|
5.1%
2/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Investigations
Creatinine renal clearance decreased
|
5.1%
2/39
|
5.3%
2/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Investigations
Weight increased
|
0.00%
0/39
|
5.3%
2/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.1%
2/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.3%
4/39
|
2.6%
1/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Nervous system disorders
Memory impairment
|
2.6%
1/39
|
5.3%
2/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Nervous system disorders
Syncope
|
0.00%
0/39
|
5.3%
2/38
|
0.00%
0/202
|
0.00%
0/203
|
|
Vascular disorders
Superior vena caval occlusion
|
10.3%
4/39
|
0.00%
0/38
|
0.00%
0/202
|
0.00%
0/203
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER