title: Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial.
abstract: BACKGROUND
  Paclitaxel and carboplatin given every 3 weeks is standard treatment for advanced ovarian carcinoma. Attempts to improve patient survival by including other drugs have yielded disappointing results. We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer.
  
  
  METHODS
  Patients with stage II to IV epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were eligible for enrolment in this phase 3, open-label, randomised controlled trial at 85 centres in Japan. Patients were randomly assigned by computer-generated randomisation sequence to receive six cycles of either paclitaxel (180 mg/m(2); 3-h intravenous infusion) plus carboplatin (area under the curve [AUC] 6 mg/mL per min), given on day 1 of a 21-day cycle (conventional regimen; n=320), or dose-dense paclitaxel (80 mg/m(2); 1-h intravenous infusion) given on days 1, 8, and 15 plus carboplatin given on day 1 of a 21-day cycle (dose-dense regimen; n=317). The primary endpoint was progression-free survival. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00226915.
  
  
  RESULTS
  631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population (dose-dense regimen, n=312; conventional regimen, n=319). Median progression-free survival was longer in the dose-dense treatment group (28.0 months, 95% CI 22.3-35.4) than in the conventional treatment group (17.2 months, 15.7-21.1; hazard ratio [HR] 0.71; 95% CI 0.58-0.88; p=0.0015). Overall survival at 3 years was higher in the dose-dense regimen group (72.1%) than in the conventional treatment group (65.1%; HR 0.75, 0.57-0.98; p=0.03). 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early. Reasons for participant dropout were balanced between the groups, apart from withdrawal because of toxicity, which was higher in the dose-dense regimen group than in the conventional regimen group (n=113 vs n=69). The most common adverse event was neutropenia (dose-dense regimen, 286 [92%] of 312; conventional regimen, 276 [88%] of 314). The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group (214 [69%]) than in the conventional treatment group (137 [44%]; p<0.0001). The frequencies of other toxic effects were similar between groups.
  
  
  CONCLUSIONS
  Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer.
  
  
  BACKGROUND
  Bristol-Myers Squibb.
authors.affiliation: Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. nkatsuma@ncc.go.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Makoto
authors.initials: M
authors.lastname: Yasuda
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takahashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.forename: Toshiko
authors.initials: T
authors.lastname: Jobo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Shoji
authors.initials: S
authors.lastname: Kodama
authors.forename: Eizo
authors.initials: E
authors.lastname: Kimura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ochiai
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Noda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis
chemical_list: D016190:Carboplatin; D017239:Paclitaxel