Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial

Prostate carcinoma is linked to osteoblasticmetastasis. We therefore investigated the value of bonetargetedconsolidation therapy in selected patients with advanced androgen-independent carcinoma of the prostate. 103 patients received induction chemotherapy, consisting of ketoconazole and doxorubicin alternating withestramustine and vinblastine. After two or three cycles ofinduction chemotherapy, we randomly assigned 72patients who were clinically stable or responders to receivedoxorubicin with or without strontium-89 (Sr-89) every week for 6 weeks. Overall 62 of the 103 (60%, 95% CI 50–70)patients had a 50% or greater reduction in serum prostatespecificantigen concentration that was maintained for at least 8 weeks, and 43 (42%, 32–52) had an 80% or greaterreduction. 49 (52%) patients with bone pain at registrationhad complete resolution of pain. After follow-up of 67patients until death, the estimated median survival for all103 patients was 17·5 months (range 0·5–37·7). For the36 patients randomly assigned to receive Sr-89 anddoxorubicin, the median survival time was 27·7 months(4·9–37·7), and for the 36 who received doxorubicin aloneit was 16·8 months (4·4–34·2) (p=0·0014). The hazardratio was 2·76 (95% CI 1·44–5·29). Bone-targeted consolidation therapyconsisting of one dose of Sr-89 plus doxorubicin once aweek for 6 weeks, when given to patients with stable or responding advanced androgen-independent carcinoma of the prostate after induction chemotherapy, improved overall survival.