title: Phase I and pharmacokinetic study of E7070, a novel sulfonamide, given at a daily times five schedule in patients with solid tumors. A study by the EORTC-early clinical studies group (ECSG).
abstract: BACKGROUND
  E7070 is a novel antitumor sulfonamide which blocks the cell in G1 phase. A phase I study was initiated to investigate the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of this compound when administered intravenously at a daily times five schedule once every three weeks.
  
  
  METHODS
  Patients with solid tumors not amenable to standard forms of therapy were eligible. E7070 was administered to cohorts of 3-6 patients per dose level, the starting dose was 10 mg/m2/day. Dose escalation was performed according to a Fibonacci-like scheme.
  
  
  RESULTS
  Thirty-three patients entered the study. At E7070 doses of 200 and 160 mg/m2/day dose-limiting toxicities occurred, which consisted of febrile neutropenia, thrombocytopenia. diarrhea, skin folliculitis, asthenia, and stomatitis. The pharmacokinetic profile of E7070 at this schedule is non-linear with increasing dose. A partial response was observed in a patient with heavily pretreated breast cancer. Disease stabilizations and some minor responses were also documented.
  
  
  CONCLUSIONS
  Myelosuppression is the predominant toxicity of E7070. Clinical efficacy with E7070 was observed. The recommended dose for further studies at this daily times five schedule is 130 mg/m2/day.
authors.affiliation: Department of Medical Oncology, University Medical Center St Radboud, Nijmegen, The Netherlands. c.punt@onco.azn.nl
authors.forename: C J
authors.initials: CJ
authors.lastname: Punt
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
authors.forename: B
authors.initials: B
authors.lastname: van de Walle
authors.forename: M N
authors.initials: MN
authors.lastname: Faber
authors.forename: M
authors.initials: M
authors.lastname: Ravic
authors.forename: M
authors.initials: M
authors.lastname: Campone
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C439829:N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide; D013449:Sulfonamides