A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer.
BACKGROUND
Superiority of irinotecan/cisplatin over etoposide/cisplatin was suggested in small-cell lung cancer (SCLC). This trial investigated irinotecan/carboplatin (IP) versus etoposide/carboplatin (EP).


METHODS
The interim analysis at the phase II/phase III transition point of the multicenter trial is reported. Extensive disease SCLC patients were randomized to receive carboplatin AUC 5 mg x min/ml either in combination with 50 mg/m2 of irinotecan on days 1, 8 and 15 (IP) or with etoposide 140 mg/m2 days 1-3 (EP). The primary end point was response rate and the secondary end points were toxicity and progression-free survival.


RESULTS
Seventy patients were randomized. Significant differences in grade 3 and 4 thrombopenia (17% IP versus 48% EP, P = 0.01) and neutropenia (26% IP versus 51% PE, P < 0.01) were found. Grade 3 and 4 diarrhea was more frequent with IP (18%) than with EP (6%) (P = 0.133). Response rates were 67% and 59% (P = 0.24) in the IP versus EP arm, respectively. Median progression-free survival (PFS) was 9 months (95% CI 7.1-10.9) in the IP arm and 6 months (95% CI 4.1-7.9) in the EP arm (P = 0.03).


CONCLUSIONS
IP is active, less toxic and appears to improve PFS. Based on the phase II results the trial has been extended to phase III to assess the impact on overall survival.
Schmittel
A
A
Department of Hematology, Oncology and Transfusion Medicine, Charité, Campus Benjamin Franklin, Berlin, Germany. alexander.schmittel@charite.de
Fischer von Weikersthal
L
L
Sebastian
M
M
Martus
P
P
Schulze
K
K
Hortig
P
P
Reeb
M
M
Thiel
E
E
Keilholz
U
U
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
D005047:Etoposide; D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin