Metronomic oral cyclophosphamide plus prednisone in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer.

Abstract

We evaluated the efficacy and safety of metronomic oral cyclophosphamide (CTX) and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients. We analyzed retrospectively patients with mCRPC previously treated with docetaxel, and who received metronomic CTX (from 50mg PO daily to 150mg PO, 14days/7days off) and prednisone 10mg PO daily between September 2009 and April 2014 were analyzed. The primary endpoint was prostate-specific antigen (PSA) decrease ≥50%. Secondary analysis included PSA decrease ≥30%, time-to-treatment failure (TTF) and toxicity. Demographics and baseline characteristics were summarized using descriptive statistics. PSA response and adverse events were reported as relative rates. Kaplan-Meier estimates were calculated and plotted for time-to-event endpoints. Forty patients were evaluated. The median age was 69years old (52-86), 12 (30.0%) patients presented a Karnofsky performance status (KPS) of <80%, and 34 (85%) presented with bone with or without nodal metastases. Median pre-treatment PSA was 192ng/dL (7-2696ng/dL). All patients were previously exposed to docetaxel, including 33 (82.5%) with docetaxel-refractory disease. PSA response rate was achieved in eight (20.0%) out of 40 patients. Additionally, PSA declines of ≥30% occurred in 14 (35.0%) patients. The median TTF was 3months (95% confidence interval 2.5-3.5). The treatment was well tolerated. Grade 3/4 lymphopenia was reported in 11 (27.5%) patients and was the only grade 3-4 toxicity reported. Metronomic oral CTX showed activity and safety in docetaxel-pretreated mCRPC patients. This regimen deserves further investigation in this setting.