Clinical Cancer Research, Vol 4, Issue 5 1193-1201, Copyright © 1998 by American Association for Cancer Research

ARTICLES

Phase I study of suramin combined with doxorubicin in the treatment of androgen-independent prostate cancer

SM Tu, LC Pagliaro, ME Banks, RJ Amato, RE Millikan, NA Bugazia, T Madden, RA Newman and CJ Logothetis
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

In this study, we determined the maximum tolerated plasma concentration of suramin (within the predetermined study target range) when combined with doxorubicin in the treatment of androgen-independent prostate cancer. Twenty-four patients received suramin dosages based on proportional adjustment of the steady-state plasma suramin concentration to achieve the targeted plasma concentrations of 50-100, 101-150, 151-200, or 201-250 microg/ml. Doxorubicin (20 mg/m2) was administered i.v. over 24 h at weekly intervals. Suramin was given i.v. over 2 h twice weekly. Patients received treatment until dose-limiting toxicity or disease progression. Side effects similar to those reported for suramin and doxorubicin administered as individual agents were observed. Dose-limiting motor neuropathy developed in three patients (13%). Twelve of 24 evaluable patients (50%; 95% confidence interval, 28-71%) and 6 of 10 evaluable patients (60%; 95% confidence interval, 26-88%) had a >50% decrease of prostate-specific antigen and measurable lesions, respectively. The maximum tolerated plasma level of suramin when combined with doxorubicin was 151-200 microg/ml. Future studies on suramin combined with doxorubicin or other agents could be performed using a fixed dosing scheme with a targeted suramin steady-state plasma concentration of 200 microg/ml.

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