Phase II study of irinotecan (CPT-11) as salvage therapy for advanced nasopharyngeal carcinoma (NPC)

5576 Background: Advanced NPC is chemosensitive and responsive even to third-line salvage regimen, therefore the continued search for active agents to enhance salvage potential. Topoisomerase I targeters have been shown to induce apoptosis in NPC cell lines in in-vitro experiments. This phase II study was designed to evaluate efficacy and safety of irinotecan in patients with advanced NPC. The pharmacokinetic and pharmacogenetic study component is reported separately. Methods: Eligibility criteria included AJCC stage IVC nasopharyngeal undifferentiated carcinoma, ECOG performance status (PS) 0–2, progressive disease during or less than 3 months after platinum-based and/or taxane-based regimen, and bidimensionally measurable disease. Irinotecan at 100 mg/m2 was administered on days 1, 8, 15, every 28 days up to maximum of 6 cycles, or until disease progression or appearance of non-tolerable toxicity. Tumor response was evaluated after every 2 cycles based on WHO criteria. Results: Between September 2001 and November 2003, 30 patients were enrolled. Currently data is available for 25 patients. Patient characteristics included mean age 50.9 (standard deviation - SD 7.5), 21 males; 4 females, 23 (92%) are Chinese, 22 (88%) had ECOG PS 0–1, and a mean 2.0 (SD 1.8) prior lines of chemotherapy. To date, all 25 patients are evaluable for toxicity with a mean 3.0 (SD 1.6) cycles of irinotecan administered. Severe toxicities of greater than grade 3 (WHO) included: grade 3 neutropenia –3 (12%), grade 3 anemia –5 (20%), grade 3 and 4 diarrhea –2 (8%) and 1 (4%) respectively, grade 3 alkaline phosphatase elevation –2 (8%). With a median follow up of 183 days (range 8 –476 days), outcome data is currently available for 23 patients. Best responses included 4 (17%) partial responses, 1 (4%) stable disease and 18 (78%) progressive disease. By Kaplan-Meier method, median progression free survival was 111 days and median overall survival was 303 days. Conclusions: Preliminary results from this trial suggest that irinotecan is an active agent as salvage treatment with modest toxicity in patients with advanced NPC refractory to platinum/taxane-based chemotherapy. No significant financial relationships to disclose.