Abstract
This study, a phase III multicenter randomized trial opened by ECOG in April 1983 and closed in June 1986 was designed to evaluate whether a combination of doxorubicin and an intravenous formulation of diethylstilbestrol diphosphate (DES) was superior to doxorubicin alone in men with hormone refractory prostate cancer. All patients received doxorubicin at a dose of 50 mg/m2 iv every 3 wk either alone or with 1 g DES iv daily for 5 d followed by 1 g iv twice weekly for four cycles (12 wk).
The 51 evaluable patients with visceral metastases displayed a significantly increased response rate (27% vs 63%) on the combined therapy arm (p=0.04). However, the 111 evaluable patients with osseous disease exhibited no difference in response rate between either arm with a p-value of >0.99. Similarly, clinical response rates revealed no difference between the two arms.
Cases of cardiac toxicity graded as severe, life threatening, or lethal in the combined therapy arm were 10 times more frequent in the combined-therapy arm than in the doxorubicin-alone group (6.75% compared to 0.7%). This difference was statistically significant (p=0.0041). All of the cases of superficial and deep venous thrombosis occurred on the combined-therapy arm. There were no other significant differences in the numbers of grade 3 or 4 toxic events. The most common toxicity was hematologic.
Failure-free survival duration did reach statistical significance in the combined-therapy group (p=0.012), although the actual durations were short (2.6–3.2 mo). There was no difference in overall survival between the two groups.
Similar content being viewed by others
References
Jemal, A., et al. (2002). Cancer Statistics CA 52:25.
Crawford, E.D., et al. (1989). A controlled trial of leuprolide with and without flutamide in prostate carcinoma. N. Engl. J. Med. 321:419–429.
Huggin, C. and Hodges, C.V. (1941). Studies on prostate cancer; effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1:293–297.
Scher, H.I., et al. (1994). Therapeutic Alternatives for Hormone Refractory Prostatic Cancer. Semin. Urol. 10:55–64.
Rohlf, P.L. and Flocks, R.H. (1969). Stilphostrol therapy in 100 cases of prostatic carcinoma. J. Iowa Med. Soc. 54:1096.
Lee, J.W. (1974). Medical management of advanced prostatic carcinoma with Stilphostrol. Connecticut Med. 38:221.
Hawtrey, C.E., et al. (1976). Paraplegia and paraparesis due to prostatic cancer. Use of intravenous diethylstilbestrol diphosphate. Urology 7:598.
Susan, L., Roth, R.B. and Atkins, W.E. (1976). Regression of prostatic cancer metastases by high doses of diethylstilbestrol diphosphate. Urology 7:598.
Band, P.R., Banerjee, T.K. and Patwardhan, V.C. (1973). High dose diethylstilbestrol diphosphate therapy of prostatic cancer after failure of standard doses of estrogens. Can. Med. Assoc. J. 109:697.
Citrin, D.L., Hogan, T.F. and Davis, T.E. (1983). Chemohormonal therapy of metastatic prostate cancer. A pilot study. Cancer 52(3):410–414.
Mehta, C.R., Patel, N.R. and Tsiatis, A.A. (1984). Exact significance testing to establish treatment equivalence with ordered categorical data. Biometrics 40:819–825.
Kaplan, E.L. and Meier, P. (1958). Non parametric estimation of incomplete observations. J. Am. Statist. Assoc. 53:457–481.
Mantel, N. (1966). Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 50:163–170.
Bailer, J.C., III and Byar, D.P. (1970). Estrogen treatment for cancer of the prostate. Early results with 3 doses of diethylstilbestrol and placebo. Cancer 26:257–261.
Byer, D.P. and Corle, D. (1988). Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urologic Research Group studies. Natl. Cancer. Inst. Monogr. 7:165–170.
Robinson, M.R.G. (1988). EORTC Protocol 30805: a phase II trial comparing orchiectomy and cyproterone acetate and low dose Stilbestrol in the management of metastatic carcinoma of the prostate, in Management of Advanced Cancer of the Prostate and Bladder (P.H. Smith and M. Pavone-Macaluso, eds), pp101–110. EORTC Genitourinary Group Monograph 4, Alan R. Liss, New York.
Robertson, C.N., et al. (1996). Induction of apoptosis by diethylstilbesrol in hormone insensitive prostate cancer cells. J. Natl. Cancer Inst. 88:908–917.
Jaziech, A.R., et al. (1994). Clinical efficacy of diethylstilbestrol treatment in post-orchiectomy progressive prostate cancer. Proc. Am. Assoc. Cancer Res. 35:233.
Tannock, I.F., et al. (1996). Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J. Clin. Oncol. 14(6):1756–1764.
Petrylak, D.P., et al. (1999). Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer. J. Clin. Oncol. 17:958–967.
Author information
Authors and Affiliations
Additional information
This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service grants CA23318, CA17145, CA21076, CA25988, CA66636, CA21115 from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
Deceased.
Rights and permissions
About this article
Cite this article
Leaf, A.N., Propert, K., Corcoran, C. et al. Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882). Med Oncol 20, 137–145 (2003). https://doi.org/10.1385/MO:20:2:137
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/MO:20:2:137