title: Phase I study of combination chemotherapy using irinotecan hydrochloride and nedaplatin for advanced or recurrent cervical cancer.
abstract: OBJECTIVE
  We performed a phase I clinical study to evaluate combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin (CPT-11/nedaplatin) for cervical cancer.
  
  
  METHODS
  This study included patients with primary or recurrent cervical cancer. The regimen for CPT-11/nedaplatin therapy consisted of CPT-11 administered 3 times over 2 weeks (days 1, 8 and 15) and nedaplatin infused intravenously as a single dose (day 1). This course was repeated at 4-week intervals. The step 1 doses of the two agents were 50 mg/m(2), respectively. Dose escalation was performed in tandem. Plasma CPT-11, SN-38, total platinum, and filterable platinum levels were measured.
  
  
  RESULTS
  In step 3 (CPT-11, 60 mg/m(2); nedaplatin, 60 mg/m(2)), dose-limiting toxicity was observed in 2 of 3 patients. The step 3 doses were regarded as the maximum tolerated doses. The incidences of grade 3/4 adverse events in the first courses (n = 12) [and all courses (n = 45)] were: leukopenia 33% (22%), neutropenia 42% (31%), anemia 17% (20%), nausea 8% (7%), and diarrhea 8% (7%). Following CPT-11 administration, the mean areas under the curve (AUC; ng.h/ml) of SN-38 were 0.11 at 50 mg/m(2) and 0.17 at 60 mg/m(2). Following nedaplatin administration, the mean AUCs (microg x h/ml) of filterable platinum were 6.0 at 50 mg/m(2), and 6.0 at 60 mg/m(2). The response rate was 50% (2 complete responses and 2 partial responses).
  
  
  CONCLUSIONS
  The recommended doses of CPT-11 and nedaplatin for a phase II clinical study were established as 50 and 60 mg/m(2), respectively.
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical School, Tochigi, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Machida
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ohwada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Ryo
authors.initials: R
authors.lastname: Konno
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Kita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Komiyama
authors.forename: Mikio
authors.initials: M
authors.lastname: Mikami
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009944:Organoplatinum Compounds; D000077146:Irinotecan; C053989:nedaplatin; D002166:Camptothecin