Initial results of a phase II study of biweekly pemetrexed and gemcitabine in patients with advanced NSCLC
7128 Background: Pemetrexed (P), a multi-targeted antifolate, is synergisitic with gemcitabine (G) in preclinical models. A phase I study examining a biweekly schedule established a recommended phase 2 dose of G 1500 mg/m2 followed by P 500mg/m2. Methods: Patients with Stage IIIB (with pleural effusion) or IV NSCLC, ECOG PS of 0 or 1, no prior systemic chemotherapy, immunotherapy, or biological therapy were enrolled. G was infused over 30 minutes, followed immediately by P given intravenously over 10 minutes once on day 1 every 14 days. Cycles were repeated until 12 treatments or progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Results: Data on 53 patients (29 male, 24 female) are currently available. Median age: 64 (range: 35, 80), ECOG performance status 0:1 = 38%:60%, Stage IIIB:IV = 19%:81%. Three hundred twelve cycles of treatment were administered with 14 dose reductions (26.4%); median number of doses was 5 for both G and P, and median dose intensity was 98.05% for both G and P. Response data included 1 complete response (1.9%), 14 partial responses (26.4%), 24 stable diseases (45.3%), and 10 progressive diseases (18.9%), with a response rate of 28.3% (95% CI: 16.8–42.3%). Patient-based Grade 3/4 hematologic events included febrile neutropenia (9.4%), neutropenia (28.3%), and thrombocytopenia (1.9%). Grade 3/4 non-hematologic events included fatigue (22.6%), dyspnea (7.5%), dehydration (7.5%), diarrhea (5.7%), constipation (3.8%), and pneumonia (1.9%). Preliminary median survival was 7.8 months (95% CI: 6.0–10.8) with 43.4% patients censored and median TTPD was 4.6 months (95% CI: 2.8–6.1). Conclusion: Biweekly G and P appear to be well tolerated in advanced NSCLC. A clinical benefit rate (ORR + SD) of 73.6% indicates activity in patients with advanced NSCLC. The dose intensity for biweekly G and P is higher than a previously reported 6-cycle, 21-day regimen with median dose intensity of 83.2% for P and 82.2% for G (West, et al. Proc ASCO 2005; 7117). [Table: see text]