title: Platinum-based adjuvant chemotherapy on moderate- and high-risk stage I and II epithelian ovarian cancer patients. Long-term single institution experience and literature review.
abstract: BACKGROUND
  Although the optimal management of women with FIGO stages I and II epithelial ovarian cancer (EOC) is still controversial, platinum-based adjuvant chemotherapy (CT) is the mainstay of treatment. Suboptimal survival results have led to major efforts to identify prognostic factors, improve surgical staging and develop adjuvant therapies to improve patients' outcomes.
  
  
  METHODS
  We evaluate in a retrospective study clinical efficacy and the toxicity profile of a platinum-based adjuvant CT in FIGO stages I and II EOC treated at our institution from March 1984 to December 2006. Grade I FIGO stages IA-IB were excluded from the analysis. In the first period (1984-1997), patients received a platinum-based regimen without taxanes. In the second period from 1997 onwards, patients were treated with carboplatin and paclitaxel. Four to six cycles of adjuvant CT were administered. Potential predictive factors of efficacy and the role of paclitaxel addition were also analysed.
  
  
  RESULTS
  One hundred and fifty-eight patients (60 treated with paclitaxel) met inclusion criteria and were evaluable. Median age at diagnosis was 53.7 years (range 19-81) and most patients had an Eastern Cooperative Oncology Group performance status score (ECOG) of 0-1 (91.8%); 82.9% patients had pathological stage I and 17.1% pathological stage II. With a median follow up of 8.34 years (range 4.4-11.6), 103 patients (74.1%) were free of disease and 110 of them were alive (79.1%). Median relapse-free survival (RFS) and median overall survival (OS) had not been reached at the time of the analysis. No survival difference was found between paclitaxel and carboplatin combination or non-paclitaxel-containing regimens. Statistically significant prognostic factors for better RFS in the multivariate analysis were: ECOG 0 (p=0.023; HR 0.32; 95% CI 0.17-0.57); FIGO I stage (p<0.001; HR 0.30; 95% CI 0.15-0.58); I-II histological grade (p=0.005; HR 0.38; 95% CI 0.19-0.75); mucinous histology (p=0.013; HR 0.28; 95% CI 0.13-0.53); non-surgical adherences (p<0.002, HR 0.32; 95% CI 0.15-0.54); paracolic gutters inspection (p=0.033; HR 0.50; 95% CI 0.26-0.95) and liver surface biopsies (p=0.048; HR 0.64; 95% CI 0.41-0.98).Toxicity was generally mild and non-haematologic events were the most commonly found (62.9% of the total). The most frequent haematologic toxicities were neutropenia (41.7% in all grades, 9.5% grade 3-4) and anaemia (29.1% in all grades, 3.2% grade 3-4).
  
  
  CONCLUSIONS
  The long-term outcome of this series is comparable to the published evidence and reflects the limited activity of platinum-based CT in the adjuvant setting. The potential survival advantage of the addition of paclitaxel to carboplatin cannot be definitively answered due to the small number of patients, the limited follow-up and the retrospective nature of the study. More effective and specific treatments are clearly required, in particular for those patients with stage II and undifferentiated tumours. Quality of surgery entails prognostic value.
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: García-Sáenz
authors.forename: Ana
authors.initials: A
authors.lastname: Custodio
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Vidart
authors.forename: Pluvio J
authors.initials: PJ
authors.lastname: Coronado
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Sara
authors.initials: S
authors.lastname: López-Tarruella
authors.forename: Javier
authors.initials: J
authors.lastname: Puente
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002173:Cancer Care Facilities; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D010052:Ovariectomy; D017671:Platinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D017671:Platinum Compounds