title: Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study.
abstract: OBJECTIVE
  Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome "resistance" in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting.
  
  
  METHODS
  Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively.
  
  
  RESULTS
  Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses.
  
  
  CONCLUSIONS
  Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment.
authors.affiliation: *Department of Oncology, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom; †Cancer Research United Kingdom Cambridge Institute, University of Cambirdge, Li Ka Shing Centre, Cambridge, United Kingdom; ‡Department of Radiology, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom; §Department of Oncology, University of Cambridge, Cambridge, United Kingdom; and ∥Department of Histopathology, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Sayal
authors.forename: Ioannis
authors.initials: I
authors.lastname: Gounaris
authors.forename: Bristi
authors.initials: B
authors.lastname: Basu
authors.forename: Sue
authors.initials: S
authors.lastname: Freeman
authors.forename: Penny
authors.initials: P
authors.lastname: Moyle
authors.forename: Karen
authors.initials: K
authors.lastname: Hosking
authors.forename: Mahesh
authors.initials: M
authors.lastname: Iddawela
authors.forename: Mercedes
authors.initials: M
authors.lastname: Jimenez-Linan
authors.forename: Jean
authors.initials: J
authors.lastname: Abraham
authors.forename: James
authors.initials: J
authors.lastname: Brenton
authors.forename: Helen
authors.initials: H
authors.lastname: Hatcher
authors.forename: Helena
authors.initials: H
authors.lastname: Earl
authors.forename: Christine
authors.initials: C
authors.lastname: Parkinson
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D015251:Epirubicin; D000069287:Capecitabine; D002945:Cisplatin