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Toxicity, Efficacy, and Pharmacology of Suramin in Adults With Recurrent High-Grade Gliomas

From the Johns Hopkins Oncology Center, Baltimore, MD; Moffitt Cancer Center, Tampa, FL; Wake Forest University, Winston-Salem, NC; and Northwestern University, Chicago, IL.

Address reprint requests to Stuart A. Grossman, MD, The Johns Hopkins Oncology Center, 1650 Orleans St, Rm G93, Baltimore, MD 21231; email: grossman{at}jhmi.edu

PURPOSE: To determine the toxicity, efficacy, and pharmacology of suramin in patients with recurrent or progressive recurrent high-grade gliomas.

PATIENTS AND METHODS: Fifty adults were to receive suramin. However, if no responses were seen in the first ten patients, the study was to be terminated. A total of 12 patients were enrolled onto this trial. Ten patients had glioblastoma multiforme, and 11 had received prior nitrosoureas.

RESULTS: Drug-related toxicities were modest and reversible. Three patients developed grade 3 to 4 neutropenia, constipation, diarrhea, or nausea. No CNS bleeding was observed. Median time to progression was 55 days (range, 17 to 242 days) and median survival was 191 days (range, 42 to 811 days). No partial or complete responses were seen at 12 weeks. However, the clinical outcome of three patients suggests that evidence of suramin activity may be delayed. One patient who "progressed" after 12 weeks of suramin had a subsequent marked reduction in tumor size and has maintained an excellent partial response for over 2 years without other therapy. Two others had disease stabilization and lived for 16 and 27 months. Pharmacokinetics from 11 patients revealed that all reached target suramin concentrations.

CONCLUSION: This study demonstrates that suramin is well tolerated by patients with recurrent high-grade gliomas and may have efficacy in this disease. Its pharmacology seems unaffected by anticonvulsants. As a result of this data, suramin and radiation are now being administered concurrently to patients with newly diagnosed glioblastoma multiforme, with survival as the primary outcome.

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