title: Phase I study of low-dose suramin as a chemosensitizer in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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 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.
  
  
  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.
authors.affiliation: 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, USA. villalona-1@medctr.osu.edu
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
authors.forename: M Guillaume
authors.initials: MG
authors.lastname: Wientjes
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Steven
authors.initials: S
authors.lastname: Kanter
authors.forename: Donn
authors.initials: D
authors.lastname: Young
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Murgo
authors.forename: Beth
authors.initials: B
authors.lastname: Fischer
authors.forename: Carrie
authors.initials: C
authors.lastname: DeHoff
authors.forename: Danny
authors.initials: D
authors.lastname: Chen
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: SaeHeum
authors.initials: S
authors.lastname: Song
authors.forename: Michael
authors.initials: M
authors.lastname: Grever
authors.forename: Jessie L-S
authors.initials: JL
authors.lastname: Au
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000627:therapeutic use; D013498:Suramin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D013498:Suramin; D016190:Carboplatin; D017239:Paclitaxel