Irinotecan and gemcitabine in patients with advanced non-small cell lung cancer, previously treated with cisplatin-based chemotherapy. A phase II study

Background: To evaluate the efficacy and tolerability of irinotecan plus gemcitabine administered every two weeks in patients with advanced non-small cell lung cancer (NSCLC) previously treated with cisplatin-based chemotherapy. Patients and Methods: Fifty patients with advanced NSCLC, refractory or resistant to cisplatin derivatives, were treated on an out-patient basis with irinotecan 150 mg/m(2) intravenously (i.v.) and gemcitabine 1,800 mg/m(2) i.v. on days I and 15, every two weeks. The response to treatment was evaluated every two cycles. The patients' median age was 59 years, 44 were men and 92% had a performance status (PS) of 0-1. Results: On an intent-to-treat analysis, 8 (16%) patients, [95% confidence interval (CI), 7.2% to 29.1%] achieved partial response (PR), 19 (38%) stable disease (SD) and 23 (46%) progressive disease (PD). The median time to tumor progression (TTP) was 5.5 months (range, 0.1 to 16.5 months), the median survival time was 8.1 months (range, 0.8 to 22.1 months) and the 1-year survival 36% (95% CI, 22.9% to 50.8%). Clinical benefit response, including improvement of PS, dyspnea, anorexia and fatigue, cessation of hemoptysis and fever and reduction of cough and pain, was observed in 10% to 44% of patients. No patient experienced grade 314 anemia. Grade 314 neutropenia and thrombocytopenia occurred in 7 (14%) and 8 (16%) patients, respectively. Five (10%) patients were hospitalized due to febrile neutropenia and were successfully treated with broadspectrum antibiotics and G-CSF support. One (2%) patient experienced grade 4 fatigue and discontinued treatment. Other grade 314 adverse events included diarrhea (3 cases, 2 of whom required hospitalization), alopecia (5 cases), asthenia (2 cases) and allergy (2 cases). Eight (16%) patients required a dose reduction. There were no treatment-related deaths. Conclusion: The combination of irinotecan and gemcitabine, administered every two weeks, demonstrated rather modest activity in advanced NSCLC patients who had previously been treated with cisplatin-based chemotherapy. It was well tolerated with mild toxicity and was associated with significant 1-year survival rate and symptomatic benefit response.