Feasibility study of dose-dense biweekly administered pemetrexed in patients with non-small cell lung cancer

• Main Authors: Christos Emmanouilides, Theodora Yermetaki, Anastasia Serpanou, Evdoxia Sapountzi, Polyxeni Mantziari, Iraklis Titopoulos, Dimitrios Filippou
• Format: Article
• Language: English
• Published: Elsevier 2010-01-01
• Series: Hematology/Oncology and Stem Cell Therapy
• Online Access: http://www.sciencedirect.com/science/article/pii/S1658387610500542

BACKGROUND AND OBJECTIVES: Pemetrexed is a multitargeted folate pathway inhibitor with documented activity in non-small cell lung cancer (NSCLC). The presumed maximum tolerated dose is 500 mg/m2 every 3 weeks, but pemetrexed-related toxicity is ameliorated when folate and B12 supplementation is provided and therefore a higher dose intensity may be tolerated. The current exploratory study assessed the feasibility of administration of pemetrexed at a fixed dose of 1000 mg every 2 weeks in patients with relapsed or refractory NSCLC. PATIENTS AND METHODS: The first cohort of 12 patients received pemetrexed monotherapy. No dose-limiting grade 4 toxicity was noted after 4 cycles, so the subsequent cohort of 14 patients received additional anticancer agents (bevacizumab, erlotinib, carboplatin, docetaxel, vinorelbine) given along with dose-dense pemetrexed. RESULTS: Toxicity overall was reversible and manageable. Among 19 patients who received pemetrexed either alone or with non-myelosuppressive targeted agents, there were only 2 instances of grade 4 neutropenia after prolonged treatment. Grade 3-4 hematologic toxicity was eventually noted in 11 of the 26 patients (42%; 95% confidence interval, 23% to 61%) after a median of 4 cycles (range, 2-14 cycles). There was no significant additional toxicity nor any treatment-related deaths. CONCLUSION: Our preliminary observations indicate that dose-dense pemetrexed every 2 weeks is feasible and this regimen can be used as monotherapy. These data may serve as a scaffold for combination studies.