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JNCI Journal of the National Cancer Institute 1993 85(8):611-621; doi:10.1093/jnci/85.8.611
© 1993 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 85, No. 8, 611-621, April 21, 1993
© 1993 Oxford University Press

Suramin, an Active Drug for Prostate Cancer: Interim Observations in a Phase I Trial

Mario A. Eisenberger, Leonard M. Reyno, Duncan I. Jodrell, Victoria J. Sinibaldi, Katherine H. Tkaczuk, Rajeshwari Sridhara, Eleanor G. Zuhowski, Mark H. Lowitt, Stephen C. Jacobs, Merrill J. Egorin

University of Maryland Cancer Center, Baltimore, and Division of Medical Oncology, Department of Medicine, University of Maryland School of Medicine Baltimore
Division of Developmental Therapeutics, University of Maryland Cancer Center
Division of Medical Oncology, University of Maryland Cancer Center, and Department of Epidemiology, University of Maryland School of Medicine
Department of Dermatology, University of Maryland School of Medicine
Division of Urology, Department of Surgery, University of Maryland School of Medicine
Division of Developmental Therapeutics, University of Maryland Cancer Center, and Division of Medical Oncology, Department of Medicine, University of Maryland School of Medicine

Correspondence to: Mario A. Eisenberger, M.D., University of Maryland Cancer Center, 22 South Greene St., Baltimore, MD 21201.

Background: Previous studies indicate that suramin may be an active agent for treatment of solid tumors. The clinical use of suramin is complicated by a broad spectrum of toxic effects and complex pharmacology. Studies have suggested that the dose-limiting neurotox-icity of this agent is closely related to sustained plasma drug concentrations of 350 µg/mL or more. Purpose: This phase I clinical trial in patients with solid tumors was designed to determine whether plasma concentrations resulting in both antitumor activity and manageable toxicity could be achieved with short, intermittent infusions of suramin. Methods: Thirty-seven patients, including 33 with metastatic, hormone-refractory prostate cancer, collectively received 43 courses of suramin designed to maintain a plasma concentration range of 200–300, 175–275, or 150–250 (µg/mL. Patients received a test dose of 200 mg and an initial loading dose of 1000 mg/m2 on day 1 of therapy. Subsequent suramin doses and schedules were individually determined using a strategy of adaptive control with feedback, which used a maximum a posteriori Bayesian algorithm to estimate individual pharmacokinetic parameters. Patients were treated until dose-limiting toxicity or progressive disease developed. Results: Thirty-five of the 37 study patients and 31 of the 33 with prostate cancer were assessable for toxicity and response. Treatment was discontinued in 28 patients because of dose-limiting toxicity consisting of a syndrome of malaise, fatigue, and lethargy; recurrent reduction in creatinine clearance of 50% or more; or axonal neuropathy. Evidence of major antitumor activity was observed in patients with prostate cancer treated at all three plasma drug concentrations. Measurable responses (one complete response and five partial responses) were noted in six of 12 patients with measurable disease. Twentyfour (77%) of 31 patients had a reduction in prostate-specific antigen of 50% or more, and 17 (55%) of 31 had a reduction of 75% or more. Twenty (83%) of 24 patients reported reduction in pain. Conclusions: Suramin can be safely administered as an intermittent bolus injection by use of adaptive control with feedback to control plasma drug concentrations; toxicity is significant but manageable and reversible. Suramin is active against hormone-refractory prostate cancer. Implications: Future trials should address the role and necessary extent of therapeutic drug monitoring; the optimal plasma drug concentration range and duration of therapy; and the activity of suramin in combination with other agents, in earlier stages of prostate cancer, and in other tumor types. [J Natl Cancer Inst 85:611–621, 1993]


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