Pemetrexed as second-line chemotherapy for castration-resistant prostate cancer after docetaxel failure: Results from a phase II study

ObjectiveAlthough there is no standard treatment after docetaxel failure in patients with castration-resistant prostate cancer (CRPC), second-line chemotherapy is increasingly required. Its mechanism of action and toxicity profile make pemetrexed suitable for testing in this setting.Methods and materialsPatients with docetaxel-resistant CRPC received pemetrexed 500 mg/m2 every 3 weeks for 6 courses. The usual premedication with vitamin supplementation and dexamethasone prophylaxis was regularly administered. The primary objective was to quantify the biochemical response rate.ResultsThe biochemical response rate was 10.5% (95% CI 1.3–33.1), with 2 patients showing a reduction in prostate specific antigen (PSA) of ≥50%. The null hypothesis that the PSA response rate would be less than 20% was therefore accepted, and patient accrual was stopped after the evaluation of the 19th patient. The 1-year overall survival rate was 61.5%, with a median survival of 14 months. A considerable proportion of the patients (36%) were withdrawn from the study because of hematologic and nonhematologic toxicity.ConclusionsOur experience with pemetrexed in CRPC patients appears discouraging in terms of activity and toxicity. No further studies of this drug should be performed in CRPC patients.