title: A phase II study of capecitabine in the treatment of ovarian cancer resistant or refractory to platinum therapy: a multicentre Italian trial in ovarian cancer (MITO-6) trial.
abstract: OBJECTIVE
  Capecitabine is an oral chemotherapeutic agent, already used in breast and colon cancer. Previous data showed encouraging results in the treatment of recurrent ovarian cancer. The aim of this study was to describe activity and toxicity of capecitabine in patients with platinum resistant or refractory ovarian cancer.
  
  
  METHODS
  Patients were eligible if they had cytologically or histologically proven epithelial ovarian cancer, refractory or resistant to prior platinum-containing chemotherapy. Capecitabine was administered at the dose of 1,250 mg/m(2) twice daily on days 1-14 of a 21-day cycle for a maximum of six cycles. The primary end point of the study was activity in terms of objective response rate in according to RECIST criteria. A two-stage minimax design for phase II studies was used: at least four objective responses had to be reached among 32 evaluable patients to define the treatment active.
  
  
  RESULTS
  Between March 2006 and October 2007, 36 patients were enrolled. All patients had ovarian cancer and 83.3% had previously received two or three lines of chemotherapy. Thirty-two patients were evaluable for response and included in the activity analysis. The objective response rate was 3.1% [95% exact confidence interval (CI): 0.08-16.22%], lower than the threshold required to define the treatment as active. The median progression free survival was 68 days (95% CI: 65-120). Haematological toxicity was not frequent. Nausea and fatigue were common, but never severe, and they were observed in 13 (37.1%) and 12 (34.2%) patients, respectively. Diarrhoea occurred in 11 patients (31.5%) and it was of grade 3 in 8.6% of cases. Grade 1-2 stomatitis was observed in seven patients (20%). Cardiovascular toxicity was reported in two cases, including a death for pulmonary embolism.
  
  
  CONCLUSIONS
  Capecitabine is not active in platinum resistant non mucinous ovarian cancer, producing a response rate lower than that required by study design. Further trials are not warranted in these patients.
authors.affiliation: Oncologia Medica, Ginecologia, Medicina di Laboratorio, Anatomia Patologica, Istituto Nazionale Tumori, Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Pisano
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorio
authors.forename: Enrico
authors.initials: E
authors.lastname: Breda
authors.forename: Rossella
authors.initials: R
authors.lastname: Lauria
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Laura
authors.initials: L
authors.lastname: Scaltriti
authors.forename: Simona
authors.initials: S
authors.lastname: Scalone
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.forename: Stefano
authors.initials: S
authors.lastname: Greggi
authors.forename: Gerardo
authors.initials: G
authors.lastname: Beneduce
authors.forename: Simona
authors.initials: S
authors.lastname: Losito
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.forename: Valeria
authors.initials: V
authors.lastname: Forestieri
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010349:Patient Compliance; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil