title: A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer.
abstract: OBJECTIVE
  Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer.
  
  
  METHODS
  Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1-14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety.
  
  
  RESULTS
  Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4-7]). Grade 4 neutropenia occurred in 15% of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin > or = 560 mg/m2.
  
  
  CONCLUSIONS
  The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1-14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Via P. Maroncelli 40, 47014 Meldola, FC, Italy. a.rocca@irst.emr.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Rocca
authors.forename: Roberta
authors.initials: R
authors.lastname: Maltoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Passardi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Massa
authors.forename: Michele
authors.initials: M
authors.lastname: Aquilina
authors.forename: Ruggero
authors.initials: R
authors.lastname: Ridolfi
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cecconetto
authors.forename: Samanta
authors.initials: S
authors.lastname: Sarti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pietri
authors.forename: Oriana
authors.initials: O
authors.lastname: Nanni
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D020714:Maximum Tolerated Dose; D055118:Medication Adherence; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D004317:Doxorubicin; D005472:Fluorouracil