title: A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study).
abstract: OBJECTIVE
  A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent ovarian cancer.
  
  
  METHODS
  Pegylated liposomal doxorubicin was administered intravenously on day 3 at a fixed dose of 30 mg/m(2). CPT-11 was administered intravenously on days 1 and 15, at a dose of 50 mg/m(2) on both days. One course of chemotherapy was 28 days, and patients were given a maximum of six courses, with the CPT-11 dose being increased in increments of 10 mg/m(2) (level 1, 50 mg/m(2); level 2, 60 mg/m(2); level 3, 70 mg/m(2); level 4, 80 mg/m(2)) to determine MTD and RD.
  
  
  RESULTS
  During the period from April 2010 to March 2013, three patients were enrolled for each level. In the first course, no dose-limiting toxicity occurred in any of the patients. Grade 4 neutropenia was observed in two of three patients at level 4. At level 4, the antitumor effect was a partial response (PR) in two of the three patients and stable disease (SD) in one. At level 3, one of the three patients showed PR and two had SD. At level 4, the start of the next course was postponed in two of three patients. In addition, one patient at level 4 experienced hemotoxicity that met the criteria for dose reduction in the next course. The above results suggested that administration of CPT-11 at dose level 5 (90 mg/m(2)) would result in more patients with severe neutropenia and in more patients requiring postponement of the next course or a dose reduction. Based on the above, the RD of CPT-11 was determined to be 80 mg/m(2).
  
  
  CONCLUSIONS
  The results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer is a useful treatment method with a high response rate and manageable adverse reactions. In the future phase II study, the safety and efficacy of this therapy will be assessed at 80 mg/m(2) of CPT-11 and 30 mg/m(2) of PLD.
authors.affiliation: Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan, tshoji@iwate-med.ac.jp.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Shoji
authors.forename: Eriko
authors.initials: E
authors.lastname: Takatori
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kaido
authors.forename: Hideo
authors.initials: H
authors.lastname: Omi
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Mizunuma
authors.forename: Michiko
authors.initials: M
authors.lastname: Kaiho
authors.forename: Takeo
authors.initials: T
authors.lastname: Otsuki
authors.forename: Tadao
authors.initials: T
authors.lastname: Takano
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishiyama
authors.forename: Keiya
authors.initials: K
authors.lastname: Fujimori
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077146:Irinotecan; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000077146:Irinotecan; D004317:Doxorubicin; D002166:Camptothecin