A Phase I Clinical Trial of Irinotecan and Carboplatin in Patients with Extensive Stage Small Cell Lung Cancer

作者：Crabb Simon J^*; Bradbury Jennifer; Nolan Luke; Selman Diana; Muthuramalingam Sethupathi R; Cave Judith; Johnson Peter W M; Ottensmeier Christian

来源：Chemotherapy, 2012, 58(4): 257-263.

DOI：10.1159/000341274

• Irinotecan
• Carboplatin
• Small cell lung cancer
• Phase I
• Chemotherapy

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/m(2) 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/m(2) irinotecan level (grade 3 diarrhoea) and in 2 patients at 70 mg/m(2) (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). Conclusion: Irinotecan 60 mg/m(2) 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.

• 出版日期2012