A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer.
BACKGROUND
This trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer.


METHODS
Patients were randomly assigned to receive carboplatin area under the curve 5 mg x min/ml either in combination with irinotecan 50 mg/m2 on days 1, 8, and 15 (IP) or etoposide 140 mg/m2 on days 1-3 (EP). Primary end point was progression-free survival (PFS) at 6 months. Secondary end points were overall survival (OS), response rate, and toxicity.


RESULTS
Of 226 patients, 216 were eligible. Median PFS was 6.0 months [95% confidence interval (CI) 5.0-7.0] in the IP arm and 6.0 months (95% CI 5.2-6.8) in EP arm (P = 0.07). Median survival was 10.0 months (95% CI 8.4-11.6) and 9.0 months (95% CI 7.6-10.4) in the IP and EP arm (P = 0.06), respectively. Hazard ratios for disease progression and OS were 1.29 (95% CI 0.96-1.73, P = 0.095) and 1.34 (95% CI 0.97-1.85, P = 0.072), respectively. No difference in response rates was observed. Grade 3 and 4 hematologic toxicity favored the IP arm, whereas diarrhea was significantly more frequent in the IP arm.


CONCLUSIONS
This trial failed to show superiority of irinotecan over etoposide in combination with carboplatin.
Department of Hematology and Oncology, Campus Benjamin Franklin, Charité, Berlin, Germany. alexander.schmittel@charite.de
A
A
Schmittel
M
M
Sebastian
L
L
Fischer von Weikersthal
P
P
Martus
T C
TC
Gauler
C
C
Kaufmann
P
P
Hortig
J R
JR
Fischer
H
H
Link
D
D
Binder
B
B
Fischer
K
K
Caca
W E E
WE
Eberhardt
U
U
Keilholz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology
D005047:Etoposide; D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin