title: Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group.
abstract: OBJECTIVE
  To determine whether chemotherapy-induced neutropenia (C-iN) is associated with improved survival in a population of primary advanced ovarian cancer and peritoneal carcinoma patients treated with a carboplatin plus paclitaxel chemotherapy backbone.
  
  
  METHODS
  A post-hoc exploratory analysis of Gynecologic Oncology Group (GOG) protocol 182 was performed. Landmark analysis was conducted on all patients with progression-free survival >18weeks from the time of study entry. Neutropenia was defined as the absolute neutrophil count <1000mm(3). The occurrence of C-iN was analyzed according to demographic, clinicopathologic, and therapeutic intent, including age, body surface area, and treatment arm. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate independent prognostic factors and to estimate their effects on PFS and OS.
  
  
  RESULTS
  Neutropenic data was available for 3447 patients. Neutropenic (n=3196) and non-neutropenic groups (n=251) were similar in demographic and clinicopathologic characteristics. Neutropenic patients experienced significantly improved survival compared to non-neutropenic patients with the adjusted hazard ratio (HR) for death being 0.86 (95% confidence interval 0.74-0.99; p=0.041). There was no survival benefit associated with any of the treatment arms among patients with C-iN.
  
  
  CONCLUSIONS
  These data suggest that C-iN may represent a clinical biomarker associated with a survival advantage for patients with untreated advanced ovarian cancer. The absence of C-iN may indicate under-dosing and ultimately attenuated anti-neoplastic effect in vulnerable populations.
authors.affiliation: Dept. of Obstetrics & Gynecology, University of California, Irvine Medical Center, Orange, CA 92868, USA. Electronic address: ktewari@uci.edu.
authors.forename: Krishnansu S
authors.initials: KS
authors.lastname: Tewari
authors.affiliation: Gynecologic Oncology Group Statistical & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Java
authors.affiliation: Dept. of Obstetrics & Gynecology, GYN Oncology of Miami, Miami, FL 33176, USA.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Gatcliffe
authors.affiliation: Division of Hematology-Oncology, University of Arizona Cancer Center, Tucson, AZ 85724, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bookman
authors.affiliation: Dept. of Obstetrics & Gynecology, Division of Gynecologic Oncology, University of Arizona Cancer Center, Creighton University School of Medicine, St. Joseph's Hospital & Medical Center, Phoenix, AZ 85013, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy*; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D017239:Paclitaxel
keywords: Biomarker; Chemotherapy-induced neutropenia; Ovarian cancer