Irinotecan and taxane combinations for non small-cell lung cancer

Based on nonoverlapping toxicity profiles and at least additive cytotoxicity in preclinical models, chemo-therapy regimens have been developed that feature the combination of irinotecan and a taxane drug. In the first study, the optimal doses of paclitaxel and irinotecan were 75 mg/m2 and 50 mg/m2, respectively, when chemotherapy was administered weekly for 4 consecutive weeks, followed by a 2-week rest. The dose-limit-ing toxicity for this regimen was neutropenia, and the most prominent nonhematologic toxicities were mild diarrhea and fatigue. Pharmacokinetic studies failed to demonstrate any sequence-dependent interaction be-tween these agents on the metabolism of irinotecan or its major metabolite. This regimen has been modified, with chemotherapy given on day 1 and day 8 every 3 weeks, and is being tested further in previously un-treated advanced non small-cell lung cancer (NSCLC). In a second trial, irinotecan was combined with docetaxel on a weekly schedule. When chemotherapy was given weekly for 4 weeks, followed by a 2-week rest, the recommended doses of docetaxel and irinotecan were 35 mg/m2 and 50 mg/m2, respectively. Low-grade gastrointestinal toxicity and asthenia were the dose-limiting toxicities. The treatment schedule was modified, with chemotherapy given on days 1 and 8 of a 21-day cycle, and patients are currently being treated with docetaxel 35 mg/m2 and irinotecan 65 mg/m2. Among the 10 evaluable patients with NSCLC in this second study, there was one partial response lasting 24 weeks and four patients with stable disease, including one patient who had progressive disease on a prior paclitaxel-containing regimen. The combinations of irinotecan and a taxane on a weekly schedule are active and well tolerated and deserve further evaluation in the treatment of NSCLC.