A phase I clinical trial of irinotecan and carboplatin in patients with extensive stage small cell lung cancer.
BACKGROUND
Treatment options for small cell lung cancer (SCLC) remain inadequate. Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain. We undertook a phase I trial to optimise the dose intensity of a 3-weekly irinotecan/carboplatin combination.


METHODS
Twenty patients with extensive stage SCLC received intravenous carboplatin at an area under the curve (AUC) of 5 on day 1, and irinotecan in 40-70 mg/m2 dose levels on days 1 and 8, every 21 days, for up to 6 cycles.


RESULTS
Dose-limiting toxicity occurred in 1 patient at the 50 mg/m2 irinotecan level (grade 3 diarrhoea) and in 2 patients at 70 mg/m2 (grade 5 neutropenic sepsis; combined grade 4 febrile neutropenia, grade 4 diarrhoea and grade 3 thrombosis). Toxicity patterns were consistent with the expected profile for this combination. The objective response rate was 75% and the median survival was 9.3 months (95% confidence interval 7.5-11.2).


CONCLUSIONS
Irinotecan 60 mg/m2 on days 1 and 8 combined with carboplatin AUC 5 every 21 days is recommended for phase II evaluation. This regimen has clinical activity, acceptable toxicity and greater dose intensity over those currently tested in phase III trials.
Department of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK. S.J.Crabb@southampton.ac.uk
Simon J
SJ
Crabb
Jennifer
J
Bradbury
Luke
L
Nolan
Diana
D
Selman
Sethupathi R
SR
Muthuramalingam
Judith
J
Cave
Peter W M
PW
Johnson
Christian
C
Ottensmeier
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D018805:Sepsis / Q000209:etiology; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D013927:Thrombosis / Q000209:etiology
D000970:Antineoplastic Agents; D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin