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


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.


RESULTS
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).


CONCLUSIONS
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 overall survival.
Tu
S M
SM
Department of Genitourinary Medical Oncology, University of Texas, M D Anderson Cancer Center, Houston 77030, USA. stu@notes.mdacc.tmc.edu
Millikan
R E
RE
Mengistu
B
B
Delpassand
E S
ES
Amato
R J
RJ
Pagliaro
L C
LC
Daliani
D
D
Papandreou
C N
CN
Smith
T L
TL
Kim
J
J
Podoloff
D A
DA
Logothetis
C J
CJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013326:Strontium Radioisotopes / Q000627:therapeutic use*; D016019:Survival Analysis; D013781:Texas / Q000453:epidemiology
D000970:Antineoplastic Agents; D013326:Strontium Radioisotopes; D004317:Doxorubicin; D017430:Prostate-Specific Antigen