title: Area under the curve calculation of nedaplatin dose used in combination chemotherapy with irinotecan in a phase I study of gynecologic malignancies.
abstract: OBJECTIVE
  Although the pharmacokinetic mechanism of nedaplatin (NDP) is similar to carboplatin, the dose of NDP is typically determined by body surface area and not by the area under the curve (AUC). We conducted a phase I study to determine the AUC-calculated optimal dosage of NDP used in combination chemotherapy with irinotecan (CPT-11) for gynecologic malignancies.
  
  
  METHODS
  A total of 15 patients who were to undergo combination chemotherapy consisting of NDP and CPT-11 were enrolled in this study. The dose of CPT-11 was administered at a fixed dose of 60 mg/m(2) and that of NDP was gradually increased from 8 to 12 μg h/mL (AUC). The individual dose of NDP was calculated based on creatinine clearance of the patient according following formula: Dose(NDP) = AUC × CL(NDP), where CL(NDP) = 0.0738 × creatinine clearance + 4.47 (Ishibashi's formula).
  
  
  RESULTS
  One patient had dose-limiting toxicity (DLT) at level 1, and two patients suffered DLT at level 3. The dosage of NDP at AUC 12 was determined to be the maximum tolerated dose in combination chemotherapy with CPT-11, even though only two of the six patients showed DLT at level 3.
  
  
  CONCLUSIONS
  The recommended dosage of NDP calculated by AUC with Ishibashi's formula was set to AUC 10 in combination chemotherapy with CPT-11.
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishimachi, Yonago 683-8504, Japan. mshima12@med.tottori-u.ac.jp
authors.forename: Muneaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Oishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itamochi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Machida
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.forename: Tasuku
authors.initials: T
authors.lastname: Harada
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Junzo
authors.initials: J
authors.lastname: Kigawa
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D014644:Genetic Variation; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D009944:Organoplatinum Compounds; D000099148:UGT1A1 Enzyme; C053989:nedaplatin