Out-patient low-dose oral chemotherapy in hormone refractory prostate carcinoma (HRPC) patients unfit for hospital admittance.

Objectives: Well tolerated out-patient regimens for HRPC chemotherapy in elderly patients with geographical difficulties and/or unwilling hospital admission are needed. The aim of the present study was to investigate the safety and efficacy of a low-dose oral combination of estramustine phosphate (EMP) and etoposide (VP16). Patients: Fifty-six HRPC patients, median age 75 years, were randomized between daily EMP (10mg/kg) – arm A, and low-dose EMP (3mg/kg) plus VP16 (25mg/mq) 2 weeks monthly – arm B. Randomization ratio was 2:3. Median PSA was 41.1 ng/ml. Baseline characteristics between the 2 groups were similar. LHRH therapy was maintained. Antiandrogen was stopped one month before entry. Results: Seven patients went off study for protocol violation. Treatment interruption due to toxicity was necessary in 6 patients (30%) of arm A and 5 (17.2%) of arm B. The low dose combination was better tolerated with a significant advantage in terms of time to treatment interruption (any reason) (p=0.01) and time to treatment interruption for toxicity (6 vs 12 months; p=0.02). Hospital admission due to toxicity was never required for arm B patients and there were no treatment-related deaths. PSA reduction of more than 50% was obtained in 3 (15%) and 12 (41.4%) patients of arm A and B respectively. Improvement in PS and pain was observed in 5 (25%) and 13 (44,8%), and in 12 (60%) and 22 (75.8%) patients of arm A and B respectively. Ten patients (50%) of arm A and 15 (51.7%) of arm B progressed with a median time to progression of 3 and 9 months respectively. Median progression free survival and median overall survival were 6 and 15 months (p= 0.02) and 13 and 17 months (p=0.63) respectively. Conclusions: Low-dose oral combination of EMP and VP16 can be safely administered at home for prolonged therapy periods in elderly patients. Symptoms and QoL are improved and time to progression and survival are not different from those obtained by other full dose chemotherapeutic regimens, although accompanied by a lower PSA response. This regimen is better tolerated than full those EMP and might represent a treatment option for patients who can not be submitted to regimens requiring hospital admission.