title: Prognostic factors from a randomized phase III trial of paclitaxel and carboplatin versus paclitaxel and cisplatin in metastatic or recurrent cervical cancer: Japan Clinical Oncology Group (JCOG) trial: JCOG0505-S1.
abstract: OBJECTIVE
  The Japan Clinical Oncology Group (JCOG) trial JCOG0505 demonstrated the statistically significant non-inferiority of paclitaxel plus carboplatin (TC) to paclitaxel plus cisplatin (TP) in terms of overall survival (OS) in metastatic or recurrent cervical cancer. In that trial, patients were randomly assigned, adjusting for institution and known prognostic factors. The objective of this ancillary study was to evaluate the appropriateness of the adjustment factors used to have randomly assigned treatments and to investigate new potentially useful prognostic factors of paclitaxel plus platinum for future randomized trials in metastatic or recurrent cervical cancer.
  
  
  METHODS
  The study subjects comprised 244 eligible patients in the JCOG0505 who were merged to have received either TC or TP. The effects of the following factors on OS were investigated using a Cox regression model taking into consideration the adjustment factors used in randomization in this trial (e.g., performance status [PS]) and other baseline factors, including platinum-free interval (PFI), pretreatment hemoglobin levels (PHLs), and pretreatment platelet counts (PPCs).
  
  
  RESULTS
  The median follow-up was 17.6 months, and median OS was 18.0 months. The hazard ratio was 1.83 in patients with a PS of 1 or 2 (vs. 0; P = 0.0004; 95 % confidence interval [CI] 1.31-2.55), 2.92 in patients with a PFI of <6 months (vs. PFI of ≥12 months; P < 0.0001; 95 % CI 1.73-4.91), 2.09 in patients with a PFI of <12 months (vs. PFI of ≥12 months; P = 0.0034; 95 % CI 1.28-3.44), and 0.69 in patients with PHL higher than or equal to the median value (vs. less than the median; P = 0.016; 95 % CI 0.51-0.93). No significant differences were obtained for PPC or the other known factors.
  
  
  CONCLUSIONS
  In addition to the known prognostic factor of PS, which was used as an adjusting factor, a PFI of <12 months and lower PHL were newly demonstrated to be associated with poor outcomes in patients with metastatic or recurrent cervical cancer. These new prognostic factors should be validated in future prospective trials.
  
  
  BACKGROUND
  UMIN-CTR[ http://www.umin.ac.jp/ctr/ ] ID: C000000335.
authors.affiliation: Department of Obstetrics and Gynecology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan. shinshin@med.kurume-u.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Nishio
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku Medical and Pharmaceutical University Hospital, 1-12-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8512, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kitagawa
authors.affiliation: JCOG Data Center, Center for Research Administration and Support, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.affiliation: Department of Obstetrics and Gynecology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Ushijima
authors.affiliation: Department of Obstetrics and Gynecology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Kamura
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D017567:Karnofsky Performance Status; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D010976:Platelet Count; D011379:Prognosis; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D006454:Hemoglobins; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin
keywords: Cervical cancer; Metastatic; Platinum-free interval; Pretreatment hemoglobin level; Recurrent