title: Phase I study of single-dose oxaliplatin in Japanese patients with malignant tumors.
abstract: BACKGROUND
  Oxaliplatin, a platinum compound, has been commonly used around the world for treating advanced colorectal cancer. The generally recommended dose and schedule of oxaliplatin monotherapy is 130 mg/m(2) every 3 weeks. This trial was conducted to evaluate the safety and pharmacokinetics of oxaliplatin monotherapy in Japanese patients with solid tumors.
  
  
  METHODS
  Oxaliplatin was administered as a 2-h intravenous infusion every 3 weeks at a dose of 90 and 130 mg/m(2). Blood was collected to determine the total platinum and the ultrafiltrate platinum concentrations in plasma in all cycles.
  
  
  RESULTS
  Nine patients were enrolled; three were given oxaliplatin monotherapy at 90 mg/m(2) and six received 130 mg/m(2). All tumors were colorectal cancer. The major adverse reactions included myelosuppressive, neurological and gastrointestinal toxicities, although most were grades 1 and 2 at both dose levels. Peripheral sensory neuropathy of without movement disturbance (grade 1 or 2) was observed in all patients at both dose levels. The 130 mg/m(2) dose level was not found to be the maximum tolerated dose, but was judged to be the recommended dose. No objective responses were seen and five cases of no change were observed. A bi-exponential open model best described the disappearance of platinum in the plasma, and a tri-exponential open model best described the disappearance of ultrafilterable platinum in the plasma at both dose levels. No racial difference was suggested in the pharmacokinetics of oxaliplatin.
  
  
  CONCLUSIONS
  The oxaliplatin monotherapy dose schedule of 130 mg/m(2) every 3 weeks, recommended worldwide, is acceptable for Japanese patients.
authors.affiliation: Gastrointestinal Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, 104-0045, Japan. kshirao@ncc.go.jp
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Fumio
authors.initials: F
authors.lastname: Nagashima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sano
authors.forename: Manabu
authors.initials: M
authors.lastname: Mutoh
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
mesh_terms: D000328:Adult; D000855:Anorexia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D010984:Platinum / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum