Phase I study of low-dose suramin as a chemosensitizer in patients with advanced non-small cell lung cancer.Clinical Cancer Research (2003)
Our preclinical studies have shown that acidic and basic fibroblastic growth factors confer broad spectrum chemoresistance and that low concentrations (10-50 microM) 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.
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 microM at 48 h in >or=5 of 6 patients.
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 microM at 48 h in 5 of the first 6 patients treated but also resulted in peak concentrations > 50 microM 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.
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.
Publication DateAugust, 2003
Citation InformationMiguel A. Villalona Calero. "Phase I study of low-dose suramin as a chemosensitizer in patients with advanced non-small cell lung cancer." Clinical Cancer Research (2003) ISSN: 1078-043x
Available at: http://works.bepress.com/miguel-villalonacalero/27/