PHASE-II TRIAL OF ALTERNATING WEEKLY CHEMOHORMONAL THERAPY FOR PATIENTS WITH ANDROGEN-INDEPENDENT PROSTATE-CANCER

Two distinct regimens of weekly chemotherapy for hormone-refractory pr ostate cancer were combined in an alternating schedule and tested in a Phase II trial to determine efficacy and toxic effects. Forty-six pat ients with hormone-refractory prostate cancer and rising prostate-spec ific antigen (PSA) levels entered the trial, Therapy consisted of doxo rubicin (20 mg/m(2)/week) plus oral ketoconazole (400 mg three times a day) given at weeks 1, 3, and 5 and vinblastine (5 mg/m(2)/week) plus oral estramustine (140 mg three times a day) given at weeks 2, 4, and 6, No therapy was given at weeks 7 and 8, Replacement doses of hydroc ortisone were administered throughout treatment to counteract potentia l adrenal insufficiency secondary to the ketoconazole. In 67% of patie nts (31 of 46), the PSA declined by 50% or greater for a minimum durat ion of 8 weeks (95% confidence interval, 52-80%), Among the 16 patient s with measurable soft tissue disease, there were 12 responses (75%; 9 5% confidence interval, 47-92%), The median duration of response was 8 .4 months (1.8-14.9), The median survival for the entire group was 19 months, The median survival of PSA responders has not been reached, wh ereas that of nonresponders was 13 months (P = 0.010), Seventy-six per cent of symptomatic patients noted improvement, Hematological toxicity was modest and was managed without growth factors, Peripheral edema ( 49%) and deep venous thrombosis (18%) were the most common nonhematolo gical toxicities. The alternating weekly regimen of chemohormonal ther apy is active for hormone-refractory prostate cancer, providing a high rate of symptom control, soft tissue response, and PSA decline.