title: Safety and activity of the combination of pegylated liposomal doxorubicin and weekly docetaxel in advanced breast cancer.
abstract: BACKGROUND
  The present study was designed with the aim of evaluating the tolerability and activity of pegylated liposomial doxorubicin (PLD) in combination with weekly docetaxel as first line treatment of advanced breast cancer.
  
  
  METHODS
  Fifty-seven patients entered the study. PLD was administered at escalating doses starting from 30 mg/m2, on day 1; docetaxel was administered at the fixed dose of 35 mg/m2 on days 2 and 9. A cycle of therapy consisted of 21 days.
  
  
  RESULTS
  The MTD was achieved at the dose of 40 mg/m2 of PLD, being febrile neutropenia and palmar-plantar-erythrodisesthesia (PPE) the dose-limiting toxicities (DLTs), so that the fixed dose of PLD for the Phase II study was 35 mg/m2. Forty-two consecutive patients received treatment at the established dose for a total of 194 cycles: among these, three patients were withdrawn for severe allergic reaction at the first administration of PLD. Hematological toxicity was moderate, the most common grade 1-3 non-hematological toxicities were stomatitis and PPE, occurring in 20 (47.5%) and 16 (38%) patients, respectively. No cardiac toxicity was recorded. According to the intent to treat analysis a major objective response was observed in 59.5% of patients (95% CI, 43.3-74.4%), with a median time to progression of 9 months and an estimated overall survival at 18 months of 62%.
  
  
  CONCLUSIONS
  The combination of PLD and weekly docetaxel is an effective first-line therapy for patients with advanced breast cancer. PPE and mucositis are the most relevant side effects of such a combination.
authors.affiliation: Division of Medical Oncology, San Filippo Neri Hospital, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Domenico
authors.initials: D
authors.lastname: Gattuso
authors.forename: Simonetta Chiara
authors.initials: SC
authors.lastname: Stani
authors.forename: Massimo
authors.initials: M
authors.lastname: Fanelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraù
authors.forename: Livia
authors.initials: L
authors.lastname: De Sio
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Castellana
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Domenico
authors.initials: D
authors.lastname: Priolo
authors.forename: Stefano
authors.initials: S
authors.lastname: Vitale
authors.forename: Roberta
authors.initials: R
authors.lastname: Sarmiento
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lo Vullo
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Giampietro
authors.initials: G
authors.lastname: Gasparini
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008081:Liposomes; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin