Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial.
Tu SM, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, Daliani D, Papandreou CN, Smith TL, Kim J, Podoloff DA, Logothetis CJ.
of Genitourinary Medical Oncology, University of Texas, M D Anderson
Cancer Center, Houston 77030, USA.
- Lancet 2001 Apr 14;357(9263):1210.
Prostate carcinoma is linked to osteoblastic metastasis. We therefore
investigated the value of bone-targeted consolidation therapy in
selected patients with advanced androgen-independent carcinoma of the
METHODS: 103 patients received induction chemotherapy,
consisting of ketoconazole and doxorubicin alternating with
estramustine and vinblastine. After two or three cycles of induction
chemotherapy, we randomly assigned 72 patients who were clinically
stable or responders to receive doxorubicin with or without
strontium-89 (Sr-89) every week for 6 weeks.
FINDINGS: Overall 62 of
the 103 (60%, 95% CI 50-70) patients had a 50% or greater reduction in
serum prostate-specific antigen concentration that was maintained for
at least 8 weeks, and 43 (42%, 32-52) had an 80% or greater reduction.
49 (52%) patients with bone pain at registration had complete
resolution of pain. After follow-up of 67 patients until death, the
estimated median survival for all 103 patients was 17.5 months (range
0.5-37.7). For the 36 patients randomly assigned to receive Sr-89 and
doxorubicin, the median survival time was 27.7 months (4.9-37.7), and
for the 36 who received doxorubicin alone it was 16.8 months (4.4-34.2)
(p=0.0014). The hazard ratio was 2.76 (95% CI 1.44-5.29).
INTERPRETATION: Bone-targeted consolidation therapy consisting of one
dose of Sr-89 plus doxorubicin once a week for 6 weeks, when given to
patients with stable or responding advanced androgen-independent
carcinoma of the prostate after induction chemotherapy, improved