title: Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial.
abstract: BACKGROUND
  The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned.
  
  
  METHODS
  Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status <or= 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m2, every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m2, every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0.
  
  
  RESULTS
  The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34-75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%).
  
  
  CONCLUSIONS
  This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears manageable.
authors.affiliation: Medical Oncology B, National Cancer Institute, Naples, Italy. sandro.pignata@fondazionepascale.it
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Antonella
authors.initials: A
authors.lastname: Savarese
authors.forename: Enrico
authors.initials: E
authors.lastname: Breda
authors.forename: Paolo
authors.initials: P
authors.lastname: Scollo
authors.forename: Rocco
authors.initials: R
authors.lastname: De Vivo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rossi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Donato
authors.initials: D
authors.lastname: Natale
authors.forename: Filomena
authors.initials: F
authors.lastname: Del Gaizo
authors.forename: Emanuele
authors.initials: E
authors.lastname: Naglieri
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferro
authors.forename: Pietro
authors.initials: P
authors.lastname: Musso
authors.forename: Alfonso Maria
authors.initials: AM
authors.lastname: D'Arco
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorio
authors.forename: Carmela
authors.initials: C
authors.lastname: Pisano
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Signoriello
authors.forename: Annalisa
authors.initials: A
authors.lastname: Annunziata
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery; D010052:Ovariectomy; D010292:Paresthesia / Q000139:chemically induced; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin