title: Phase I and pharmacologic study of BNP7787, a novel chemoprotector in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I trial of BNP7787 (disodium 2,2'-dithio-bis-ethane sulfonate, Tavocept™), a novel chemoprotective and antitumor enhancing agent administered in combination with paclitaxel and cisplatin. The primary aim was to determine a safe and potentially efficacious BNP7787 dose for preventing and mitigating paclitaxel- and cisplatin-induced toxicities and to evaluate for preliminary evidence of efficacy of treatment.
  
  
  METHODS
  Twenty-two patients with stage IIIB/IV non-small cell lung cancer (NSCLC) received BNP7787 alone 1 week before co-administration of BNP7787 with paclitaxel followed by cisplatin. Twenty-one patients were treated with BNP7787 in escalating doses of 4.1-41.0 g/m² concurrently with paclitaxel 175 mg/m² and cisplatin 75 mg/m² every 3 weeks.
  
  
  RESULTS
  The appropriate dose was determined to be 18.4 g/m² of BNP7787 although no dose-limiting toxicity was observed up to 41.0 g/m². Mild intravenous site discomfort, thirst, and nausea were the most common toxicities. One patient developed grade 2 skin rash, which was severe enough to preclude further study treatment. The AUC(0-inf) of the metabolite mesna was approximately 6.3% of the AUC(0-inf) of BNP7787. Co-administration of paclitaxel and cisplatin did not appear to influence the pharmacokinetics of BNP7787 and mesna. The overall response rate was encouraging; 43% including 11 patients with prior chemotherapy.
  
  
  CONCLUSIONS
  The recommended dose for phase II/III studies is 18.4 mg/m² of BNP7787 in combination with paclitaxel and cisplatin. Further studies are warranted to assess whether BNP7787 prevents and mitigates common and serious paclitaxel- and cisplatin-related side effects and enhances the efficacy of paclitaxel and cisplatin in advanced NSCLC patients.
authors.affiliation: Department of Respiratory Medicine, Kitasato University School of Medicine, Minami-ku, Kitasato, Sagamihara, Japan. masuda@med.kitasato-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
authors.forename: Frederick
authors.initials: F
authors.lastname: Hausheer
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Matsui
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Naruo
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015080:Mesna / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: C027032:2,2'-dithiodiethanesulfonic acid; D015080:Mesna; D017239:Paclitaxel; D002945:Cisplatin
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