title: Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial.
abstract: OBJECTIVE
  Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy.
  
  
  METHODS
  Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS.
  
  
  RESULTS
  Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles.
  
  
  CONCLUSIONS
  Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.
authors.affiliation: Istituto Nazionale Tumori, via Mariano Semmola, 80131 Napoli, Italy. sandro.pignata@gmail.com
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.forename: Antonella
authors.initials: A
authors.lastname: Savarese
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorio
authors.forename: Enrico
authors.initials: E
authors.lastname: Breda
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Pietro
authors.initials: P
authors.lastname: Musso
authors.forename: Luigi
authors.initials: L
authors.lastname: Frigerio
authors.forename: Pietro
authors.initials: P
authors.lastname: Del Medico
authors.forename: Alessandra Vernaglia
authors.initials: AV
authors.lastname: Lombardi
authors.forename: Antonio
authors.initials: A
authors.lastname: Febbraro
authors.forename: Paolo
authors.initials: P
authors.lastname: Scollo
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferro
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.forename: Alba
authors.initials: A
authors.lastname: Brandes
authors.forename: Alberto
authors.initials: A
authors.lastname: Ravaioli
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Valerio
authors.forename: Enrico
authors.initials: E
authors.lastname: Aitini
authors.forename: Donato
authors.initials: D
authors.lastname: Natale
authors.forename: Laura
authors.initials: L
authors.lastname: Scaltriti
authors.forename: Stefano
authors.initials: S
authors.lastname: Greggi
authors.forename: Carmela
authors.initials: C
authors.lastname: Pisano
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
authors.forename: Vanda
authors.initials: V
authors.lastname: Salutari
authors.forename: Francesco
authors.initials: F
authors.lastname: Legge
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011788:Quality of Life
chemical_list: D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin