Efficacy of Oxaliplatin Plus Pemetrexed in Chemotherapy Pretreated Metastatic Castration-Resistant Prostate Cancer

Abstract

BackgroundAlthough new androgen-targeted therapies offer prolonged survival in metastatic castration-resistant prostate cancer (CRPC), most men still face progressive disease and require additional therapy. Oxaliplatin and pemetrexed have each shown modest activity in the treatment of CRPC. Given their favorable nonoverlapping toxicity profiles, we studied them in combination. Patients and MethodsMen with CRPC whose disease had progressed on 1 or 2 previous chemotherapy regimens, including a taxane, were eligible. All participants received oxaliplatin 120 mg/m2 and pemetrexed 500 mg/m2 intravenously every 21 days. The primary end point was response rate; objective responses were determined using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, criteria and the Prostate Cancer Working Group (1999) criteria. Secondary end points included progression-free survival and OS. ResultsForty-seven men received a median of 6 cycles (range, 1-21). The overall response rate was 30% (95% confidence interval [CI], 18%-45%), including 10 men with RECIST responses of the 40 who had measurable disease (25%). Overall, 64% had a prostate-specific antigen (PSA) decline and 74% of men had clinical disease control (partial response or stable disease as their best response). Median progression-free survival was 5.8 months (95% CI, 3.8-7.6), with a median OS of 11.9 months. Six of 15 evaluable patients (40%) experienced a pain response. Nineteen patients (40%) experienced a grade 3 or 4 hematologic toxicity, and 16 (34%) experienced a grade 3 nonhematologic toxicity. One patient died while participating in the study. ConclusionCombination oxaliplatin and pemetrexed (PemOx) is an effective and tolerable second- or third-line treatment for men with CRPC.