title: Paclitaxel plus oxaliplatin for recurrent or metastatic cervical cancer: a New York Cancer Consortium Study.
abstract: OBJECTIVE
  Survival in women with recurrent or metastatic cervical cancer remains poor. More effective and less toxic regimens are needed. Cisplatin is an effective radiosensitizer, but its single agent activity in recurrent cervical cancer, especially after prior cisplatin exposure, is disappointing, with a response rate of only 13%. Oxaliplatin has preclinical activity in cisplatin-resistant tumors and may have synergic activity when combined with paclitaxel. Our objective is to determine the efficacy and toxicity of paclitaxel and oxaliplatin in patients with recurrent or metastatic cervical cancer.
  
  
  METHODS
  Patients with histologic confirmation of primary metastatic or recurrent cervical cancer not amenable to surgical management were eligible. Treatment consisted of paclitaxel 175 mg/m(2) IV and oxaliplatin 130 mg/m(2) IV every 21 days. The primary endpoints were toxicity, recorded every cycle, and response, determined by RECIST criteria and were assessed every 9 weeks, with subsequent confirmation as required. Sample size determinations were made using a Simon's two-stage design with a projected overall response proportion of 13% with cisplatin alone. Survival rates were calculated with Kaplan-Meier methods.
  
  
  RESULTS
  Of the 35 patients enrolled, 32 were evaluable. The median age was 56 (27-78); 30 had had prior radiation (23 concomitant with cisplatin). Patients completed a mean of 4.2 cycles (1-11). There were 2 complete and 5 partial responses for a total response rate of 7/32 (22%; 95% CI: 9.3%-40.0%). Eight patients had stable disease for an overall clinical benefit rate of 15/32 (47%; 95% CI: 29.1%-65.3%). The mean time to best response was 13.5 weeks (95% CI: 10.6, 16.4). The mean progression-free survival was 21 weeks (95% CI: 14.7, 27.2) and mean overall survival was 52 weeks (95% CI: 39.4, 64.8). A total of 135 cycles were administered. There were 28 (20.1%) grade 3/4 hematologic toxicities and 46 (34.1%) grade 3/4 non-hematologic toxicities, which were predominantly sensory neuropathy. There were 13 treatment delays, 4 dose reductions, and no treatment-related deaths.
  
  
  CONCLUSIONS
  The combination of paclitaxel and oxaliplatin is an effective regimen in patients with recurrent or persistent cervical cancer including a majority previously exposed to cisplatin. Further study and comparison with other platinum-based regimens is warranted.
authors.affiliation: Montefiore Medical Center/Albert Einstein College of Medicine, Suite 601, Bronx, NY 10461, USA. dykuo@montefiore.org
authors.forename: Dennis Yi-Shin
authors.initials: DY
authors.lastname: Kuo
authors.forename: Stephanie V
authors.initials: SV
authors.lastname: Blank
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: Mimi
authors.initials: M
authors.lastname: Kim
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Caputo
authors.forename: Bhavana
authors.initials: B
authors.lastname: Pothuri
authors.forename: Dawn
authors.initials: D
authors.lastname: Hershman
authors.forename: Noah
authors.initials: N
authors.lastname: Goldman
authors.forename: Percy S
authors.initials: PS
authors.lastname: Ivy
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Runowicz
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
authors.forename: Gary L
authors.initials: GL
authors.lastname: Goldberg
authors.forename: Mark H
authors.initials: MH
authors.lastname: Einstein
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017239:Paclitaxel