Researchers, Nelius T, Klatte T, de Riese W, Haynes A, Filleur S. from the Department of Urology, Texas Tech University Health Sciences Center, Lubbock, TX. studied the efficacy of cyclophosphamide (CP)-based metronomic chemotherapy in men who have docetaxel-resistant hormone-refractory prostate cancer (HRPC).
To be included in the study men have to have confirmed metastatic HRPC and have disease progression while being under docetaxel-based chemotherapy. The study’s 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 given in a metronomic manner (low dose). Treatment was continued until disease progression or intolerable side effects occurred.
A total of seventeen men 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 men had a PSA response (median 44.4%); four men had a greater than 50% response and five men had a less than 50% PSA response. Eight men eventually experienced a PSA progression. The overall survival was 24 months. Five men reported a decrease in bone pain after 4 weeks of treatment. As opposed to Jevtana (cabazitaxe) no grade 3 and 4 toxicities were noted.
Given the lack of alternative treatments this study supports the use of low-dose metronomically administered CP. It did demonstrate a level of efficacy as a second-line treatment in patients with docetaxel-resistant HRPC. Additionally, 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 immuno-regulatory and antiangiogenic potentials make Cyclophosphamideals a prime candidate for additional study for post chemotherapy and as a possible combination drug to be used with other treatment regimens.
Med Oncol. 2010 Jun;27(2):569.; , Nelius T, Klatte T, de Riese W, Haynes A, Filleur S.