title: Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study.
abstract: OBJECTIVE
  Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown.
  
  
  METHODS
  To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP.
  
  
  RESULTS
  Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP.
  
  
  CONCLUSIONS
  The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.
authors.affiliation: Istituto Nazionale Tumori, via M Semmola, 80131-Napoli, Italy; e-mail: sandro.pignata@fondazionepascale.it
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Vagno
authors.forename: Emanuele
authors.initials: E
authors.lastname: Naglieri
authors.forename: Alessandra Vernaglia
authors.initials: AV
authors.lastname: Lombardi
authors.forename: Rosalbino
authors.initials: R
authors.lastname: Biamonte
authors.forename: Marco
authors.initials: M
authors.lastname: Marinaccio
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cartenì
authors.forename: Luigi
authors.initials: L
authors.lastname: Manzione
authors.forename: Antonio
authors.initials: A
authors.lastname: Febbraro
authors.forename: Andrea
authors.initials: A
authors.lastname: De Matteis
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Gasparini
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Valerio
authors.forename: Saverio
authors.initials: S
authors.lastname: Danese
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
authors.forename: Rossella
authors.initials: R
authors.lastname: Lauria
authors.forename: Michele
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: Stefano
authors.initials: S
authors.lastname: Greggi
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel