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Phase I Study of Low-Dose Suramin as a Chemosensitizer in Patients with Advanced Non-Small Cell Lung Cancer¹

Department of Medicine and College of Pharmacy, The Ohio State University, The Arthur G. James Cancer Hospital & Richard J. Solove Research Institute, Columbus, Ohio 43210-1240, and The National Cancer Institute, Bethesda, Maryland 20892

Purpose: Our preclinical studies have shown that acidic and basic fibroblastic growth factors confer broad spectrum chemoresistance and that low concentrations (10–50 µM) of suramin, a nonspecific fibroblastic growth factor inhibitor, enhance the antitumor activity of paclitaxel in vivo. The present Phase I study evaluated low-dose suramin in combination with paclitaxel/carboplatin in advanced non-small cell lung cancer patients.

Experimental Design: Patients received suramin followed by paclitaxel (175–200 mg/m²) and carboplatin area under the concentration-time curve of 6 mg/ml/min, every 3 weeks. The initial suramin dose for the first cycle was 240 mg/m², and the doses for subsequent cycles were calculated based on the 72-h pretreatment plasma concentrations. The recommended suramin dose would yield plasma concentrations of 10–20 µM at 48 h in 5 of 6 patients.

Results: Fifteen patients (11 stage IV, 4 stage IIIB, 9 chemonaive, and 6 previously treated) received 85 courses. The most common toxicities were neutropenia, nausea/vomiting, malaise/fatigue, and peripheral neuropathy. No treatment-related hospitalizations, adrenal dysfunction, or episodes of sepsis occurred. The initial suramin dose resulted in the targeted concentrations of 10–20 µM at 48 h in 5 of the first 6 patients treated but also resulted in peak concentrations > 50 µM in all patients. Dividing the suramin dose to be administered in two doses, 24 h apart, yielded the target concentrations and avoided undesirable peak concentrations. Discernable antitumor activity occurred in 7 of 10 patients with measurable disease, including 2 with prior chemotherapy. The median time to tumor progression is 8.5 months (range, 3–27+ months) for 12 evaluable patients.

Conclusions: Low-dose suramin does not increase the toxicity of paclitaxel/carboplatin combination. The suramin dose can be calculated based on clinical parameters. Because of the preliminary antitumor activity observed, efficacy studies in chemonaive and chemorefractory patients are under way.

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