title: Phase I-II study of pegylated liposomal doxorubicin combined with weekly paclitaxel as first-line treatment in patients with metastatic breast cancer.
abstract: OBJECTIVE
  Pegylated liposomal doxorubicin (PLD) appears to be as active as doxorubicin in first-line metastatic breast cancer (MBC) patients, with lower cardiac toxicity. This phase I-II trial aimed to determine the dose limiting toxicity (DLT) and recommended dose (RD) of a first-line combination of PLD and weekly paclitaxel.
  
  
  METHODS
  MBC patients received PLD on day 1, administered over 60 minutes IV. (starting dose 30 mg/m2, escalation by 5 mg/m2 increments), and paclitaxel on days 1, 8, and 15. Initially (schedule A), paclitaxel was administered over 60 minutes (starting dose 80 mg/m2, 10 mg/m2 increments), then (schedule B) over 24 hours on day 1 (at a dose of 70 mg/m2, 10 mg/m2 increments), and in a 60 minute IV infusion at a fixed dose of 90 mg/m2 on days 8 and 15. Pharmacokinetics were assessed during cycle 1 in schedule B.
  
  
  RESULTS
  Thirty patients were treated (schedules A = 9; B = 21). Because of cutaneomucous toxicities in all patients in schedule A with discontinuation in 5 patients, schedule B was explored. Two DLTs (febrile neutropenia) occurred, with PLD 35 mg/m2 with paclitaxel 80 mg/m2 day 1 and 90 mg/m2 days 8 and 15 identified as recommended dose. Pharmacokinetic evaluation revealed an interaction, with increased levels of free doxorubicin and PLD during the paclitaxel infusion.
  
  
  CONCLUSIONS
  This combination according to schedule and dosages results in cutaneomucous and hematological toxicity, probably because of a pharmacokinetic interaction, which is poorly compatible with a good quality of life for MBC patients.
authors.affiliation: CHU de Poitiers, Poitiers, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Bourgeois
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ferru
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.forename: Thierry
authors.initials: T
authors.lastname: Delozier
authors.forename: Michèle
authors.initials: M
authors.lastname: Boisdron-Celle
authors.forename: Sophie
authors.initials: S
authors.lastname: Abadie-Lacourtoisie
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chieze
authors.forename: Virginie
authors.initials: V
authors.lastname: Chabrun
authors.forename: Erick
authors.initials: E
authors.lastname: Gamelin
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tourani
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects; D049691:History, Medieval; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D004317:Doxorubicin; D017239:Paclitaxel