No Additional Benefit of Adding Ifosfamide to Docetaxel in Castration-resistant Metastatic Prostate Cancer

Background: In the treatment of many types of cancer, combination chemotherapy has been shown to be better than single-agent chemotherapy. The aim of our phase I-II clinical trial was to assess the efficacy and toxicity of docetaxel-ifosfamide combination chemotherapy in patients with castration-resistant metastatic prostate cancer (CRPC). Patients and Methods: A total of 31 patients were enrolled to receive first-line chemotherapy consisting of 40-60 mg/m(2) docetaxel followed by 3.0 g/m(2) ifosfamide with mesna. All drugs were administered intravenously. The maximum duration of the chemotherapy was six cycles. The median age of the patients was 70 (range 58-82) years. Prostate specific antigen (PSA) responses were determined according to the PSA working group guidelines and all toxicities time-to-progression and overall survival were determined according to the WHO criteria. Results: The objective PSA response rate was 32% in 11/31 patients. The mean PSA value at baseline was 300 (range 2.5-1577) mu g/l. The overall median survival was 14.1 months; 15 patients were alive at a median follow-up time of 18 months. The observed side-effects were as expected, with grade 3-4 neutropenia developing in 38% of the cycles, whereas febrile neutropenia occurred in only 12% of the patients. The median number of administered cycles was 4.8. No acute hypersensitivity reactions were observed. Transient renal insufficiency developed in two patients, thus necessitating dose reductions. Conclusion: The combination of docetaxel and ifosfrimide seems to be well-tolerated and has some activity in patients with CRPC. However, newer docetaxel-based combination chemotherapy regimens need to be further developed in other to provide more efficacious and well-tolerated treatment options for earlier phases of CRPC.