Phase II Study of Biweekly Pemetrexed and Gemcitabine in Patients with Previously Untreated Advanced Non-small Cell Lung Cancer

Introduction: Pemetrexed and gemcitabine are safe and active non-small cell lung cancer (NSCLC) therapies when administered every 3 weeks. Biweekly scheduling was studied in this phase II trial. Methods: The primary objective was to assess the overall response rate in chemotherapy-naive patients with unresectable stage III/IV NSCLC. Patients received 500 mg/m(2) of pemetrexed intravenously and 1500 mg/m(2) of gemcitabine intravenously every 2 weeks for 8 to 12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy. Entry criteria included the following: all non-small cell histologies, measurable disease, Eastern Cooperative Oncology Group 0 to 2, and informed consent. Results: Seventy-two patients were enrolled. Baseline characteristics included the following: median age: 66 years (41-85 years); male/female: 65%/35%; Eastern Cooperative Oncology Group 0/1/2: 19%/67%/14%; and histology: adenocarcinoma (36%), large cell (18%), squamous (13%), and mixed or not specified (34%). The median number of cycles was 7 (range, 1-12). The most common (>= 5%) grade 3/4 toxicities were as follows: neutropenia (47%), leukopenia (31%), fatigue (25%), dyspnea (18%), pain (11%), and anemia (8%). Complete/partial responses for all patients: 1 patient/ 18 patients, respectively, for an overall response rate of 26% (95% confidence interval, 17-38%). Thirty-nine percentage of patients had stable disease, and 21% had disease progression (10 patients were not evaluable). Median progression-free survival was 6.2 months. One-year overall survival was 37.5%. Conclusion: Biweekly administration of pemetrexed and gemcitabine seems to be well tolerated with activity comparable with other first-line NSCLC regimens. Further study addressing whether biweekly scheduling could be an effective strategy to shorten overall treatment duration will require a randomized design.