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

• Published in: Clinical cancer research 2003-08, Vol.9 (9), p.3303-3311
• Main Authors: VILLALONA-CALERO, Miguel A, WIENTJES, M. Guillaume, SONG, Saeheum, GREVER, Michael, AU, Jessie L.-S, OTTERSON, Gregory A, KANTER, Steven, YOUNG, Donn, MURGO, Anthony J, FISCHER, Beth, DEHOFF, Carrie, CHEN, Danny, YEH, Teng-Kuang
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Area Under Curve; Biological and medical sciences; Carboplatin - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemotherapy; Drug Interactions; Female; Follow-Up Studies; Humans; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; Neoplasm Metastasis; Paclitaxel - therapeutic use; Pharmacology. Drug treatments; Suramin - pharmacokinetics; Suramin - therapeutic use; Time Factors
• ISSN: 1078-0432; 1557-3265

Purpose: Our preclinical studies have shown that acidic and basic fibroblastic growth factors confer broad spectrum chemoresistance and that low concentrations (10–50 μ m ) 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/m 2 ) 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/m 2 , 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 μ m 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 μ m at 48 h in 5 of the first 6 patients treated but also resulted in peak concentrations > 50 μ m 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.