METRONOMIC CYCLOPHOSPHAMIDE FOR PROSTATE CANCER

: Med Oncol. 2009 Apr 14. [Epub ahead of print]

Related Articles, LinkOut

Clinical outcome of patients with docetaxel-resistant hormone-refractory prostate cancer treated with second-line cyclophosphamide-based metronomic chemotherapy.

Nelius T, Klatte T, de Riese W, Haynes A, Filleur S.

Department of Urology, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 7260, Lubbock, TX, 79430-7260, USA, thomas.nelius@ttuhsc.edu.

For patients with docetaxel-resistant hormone-refractory prostate cancer (HRPC) no standard chemotherapeutic treatment exists. In this study, we evaluate the efficacy of cyclophosphamide (CP)-based metronomic chemotherapy in this patient population. Patients with metastatic HRPC with disease progression under docetaxel-based chemotherapy were eligible. The primary endpoint was prostate-specific antigen (PSA) response. Secondary endpoints were survival and toxicity. Low-dose CP (50 mg/d) and dexamethasone (1 mg/d) were administered orally in a metronomic manner. Treatment was continued until disease progression or intolerable side effects occurred. Seventeen patients were enrolled in this study. The median follow-up was 12 weeks (range: 4-60). Median age was 68 years (range: 42-85). Median PSA at study entry was 134 ng/ml (range: 46.0-6554). Nine patients had a PSA response (median 44.4%), four patients >/=50% and five patients <50%. Eight patients had a PSA progression. Overall survival was 24 months. Five patients reported a decrease in bone pain after 4 weeks' treatment. No grade 3 and 4 toxicities were noted. In this study, low-dose metronomically administered CP demonstrated efficacy as a second-line treatment in patients with docetaxel-resistant HRPC. The treatment was well tolerated and almost without toxicity. Further advantages of low-dose CP were its convenient oral administration, dosing schedule, low cost, and low-toxicity profile. These attributes in combination with immunoregulatory and antiangiogenic potentials make CP also a prime candidate for combination with other treatment regimens.