title: The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  To explore associations between histology and outcome in advanced or recurrent endometrial cancer patients participating in Gynecologic Oncology Group chemotherapy trials.
  
  
  METHODS
  Age, race, performance status, histologic type (serous=S; clear cell=CC; endometrioid=E), disease stage, and prior radiation were evaluated using various analytic methods to evaluate the probability of response and identify independent predictors of progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Single agent or combination chemotherapy regimens including doxorubicin (A) (12%), doxorubicin/cisplatin (AP) (63%), doxorubicin/paclitaxel (AT) (13%), and paclitaxel/doxorubicin/cisplatin (TAP) (11%) were used among 1203 patients treated on 4 randomized clinical trials. Breakdown of disease stage was 7.8% stage III, 22.8% stage IV, and 69.4% recurrent disease. Histologic distribution was 18% S, 3.7% CC, 8.5% mixed, 51.7% E and 18.1% other. More S/CC patients enrolled on trials with advanced stage (III-IV) disease (as opposed to recurrent disease) compared to E patients (45% vs. 24%, p<0.05). Overall response rate was 42% (E=44%, S=44%, CC=32%). Histologic type was not an independent predictor of response. Independent predictors of PFS included race, performance status, disease stage, and CC histology. Histology was also an independent predictor of OS; the relative hazard ratio for S histology was 1.2 (1.02-1.4; p=0.03), and for CC was 1.51 (1.1-2.07; p=0.01).
  
  
  CONCLUSIONS
  In patients with advanced/recurrent endometrial cancer treated with A, P and/or T, response was not associated with histology. This exploratory analysis does not support exclusion of S tumors in future trials. Poorer PFS and OS were observed in CC compared to other types, but a lack of benefit from chemotherapy was not shown, and as this histology represents such a small fraction, it does not seem feasible to have separate chemotherapy trials for CC.
authors.affiliation: Division of Gynecologic Oncology, University of Oklahoma, Oklahoma City, OK 73190, USA. scott-mcmeekin@ouhsc.edu <scott-mcmeekin@ouhsc.edu>
authors.forename: D Scott
authors.initials: DS
authors.lastname: McMeekin
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Filiaci
authors.forename: J Tate
authors.initials: JT
authors.lastname: Thigpen
authors.forename: Holly H
authors.initials: HH
authors.lastname: Gallion
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.forename: William H
authors.initials: WH
authors.lastname: Rodgers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology*; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin