Metronomic cyclophosphamide in elderly patients with advanced, castration-resistant prostate cancer

Metronomic chemotherapy-low-dose, long-term, frequently administered chemotherapy-has been found to have an important effect on the stabilization of cancer, including prostate cancer, without any highgrade toxicity. However, no data from prospective metronomic clinical trials are available in elderly patients with cancer. Anecdotal case reports and a small retrospective clinical study on metastatic melanoma have suggested metronomic chemotherapy as an alternative therapy in elderly patients requiring palliation. The present study was a retrospective review of 29 consecutive elderly patients (aged >/= 78) with advanced castration-resistant prostate cancer (CRPC) who had been treated with metronomic cyclophosphamide (50 mg per day by mouth) plus celecoxib (200 mg twice a day by mouth) and dexamethasone (1 mg once daily by mouth) at Pisa University Hospital and Livorno General Hospital. The treatment was given for at least 12 weeks. No Grade 3 or 4 hematological or nonhematological toxicities were observed in the 29 assessable patients. Four patients (14%) developed National Cancer InstituteF Common Toxicity Criteria Grade 2 anemia, and two patients (7%) developed Grade 2 thrombocytopenia (one of these patients required cyclophosphamide discontinuation). Neither major cardiovascular events nor toxicity-related deaths were observed. Overall, 18 patients (62%) experienced any reduction in PSA level (a decrease of 2% to 99%); 13 (45%) had a confirmed PSA decrease of 50% or greater. Of the 13 responders (77%), 10 had not received any prior chemotherapy, whereas the remaining three had previously received chemotherapy (median 2 lines of chemotherapy). The observed activity and toxicity profiles in the present studywere consistent with previous reports and seems to be well tolerated, safe, and active in elderly, unfit patients with CRPC.