Randomized phase II trial of irinotecan with paclitaxel or gemcitabine for non-small cell lung cancer: association of UGT1A1*6 and UGT1A1*27 with severe neutropenia.

HYPOTHESIS Irinotecan-containing regimens are known to be active and tolerable in patients with non-small cell lung cancer (NSCLC). A randomized phase II trial was conducted to evaluate the efficacy of irinotecan plus paclitaxel or gemcitabine for previously untreated stage IIIB or stage IV NSCLC. PATIENTS AND METHODS Previously untreated patients with adequate organ function who gave written informed consent were randomly assigned to receive irinotecan (50 mg/m on days 1, 8, and 15) plus paclitaxel (180 mg/m on day 1) every 4 weeks (IP group) or irinotecan (100 mg/m on days 1 and 8) plus gemcitabine (1000 mg/m on days 1 and 8) every 3 weeks (IG group). The primary endpoint was the response rate. We also evaluated the relationship of response and toxicity to polymorphisms of the uridine diphosphate glucuronosyltransferase (UGT) gene. RESULTS Eighty patients were enrolled, and 78 patients were eligible (38 in the IP group and 40 in the IG group). The response rate was 31.6% (95% confidence interval: 17.5-48.7%) in the IP group and 20.0% (9.1-35.6%) in the IG group. The median progression-free survival time was 86 days and 145 days, respectively. Both regimens were well tolerated. The most common severe adverse event was grade 4 neutropenia (36.8% and 10.0%, respectively), which was associated with UGT1A1*6 and UGT1A1*27. UGT polymorphisms did not correlate with response. CONCLUSIONS Irinotecan plus paclitaxel may be more active against NSCLC than irinotecan plus gemcitabine. The UGT1A1*6 and UGT1A1*27 genotypes might be useful predictors of grade 4 neutropenia in patients who receive irinotecan-based chemotherapy.