title: A phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline.
abstract: OBJECTIVE
  The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy.
  
  
  METHODS
  This phase-I study was performed via a two-staged dose escalation schema. The initial doses were PLD 30 mg/m2 and PTX 150 mg/m2, administered intravenously once every 21 days. The dose of PLD was escalated in increments of 5 mg/m2 until the MTD was reached, at which time the PTX was then increased in increments of 10 mg/m2 until the MTD was reached.
  
  
  RESULTS
  Twenty-three patients received between 1 and 13 treatment cycles. In stage I of the study, 14 patients received a fixed dose of PTX 150 mg/m2 while PLD escalated from 30 mg/m2. At 40 mg/m2, PLD resulted in dose-limiting toxicities (DLT) including febrile neutropenia and palmar-plantar erythrodysesthesia that occurred in two of five patients. In stage II of the study, nine patients received fixed dose of PLD 35 mg/m2 and escalating doses of PTX starting at 160 mg/m2. At PTX 170 mg/m2 and dose-limiting neutropenic fever occurred in two of five patients. Out of 19 evaluable patients, 10 (52.6%) achieved objective response (one complete response and nine partial response), and 5 had stable disease.
  
  
  CONCLUSIONS
  The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m2, respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m2) and PTX (150-160 mg/m2) constitutes an active regimen with mild toxicity that merits further study.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei 10016, Taiwan. rlhong@ha.mc.ntu.edu.tw
authors.forename: Ruey-Long
authors.initials: RL
authors.lastname: Hong
authors.forename: Ching-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Chao
authors.forename: Woei-You
authors.initials: WY
authors.lastname: Kao
authors.forename: Cheng-Hsu
authors.initials: CH
authors.lastname: Wang
authors.forename: Ruey Kuen
authors.initials: RK
authors.lastname: Hsieh
authors.forename: Wei-Shou
authors.initials: WS
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced; D005533:Foot Dermatoses / Q000139:chemically induced; D006229:Hand Dermatoses / Q000139:chemically induced; D006801:Humans; D008081:Liposomes; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D010292:Paresthesia / Q000139:chemically induced; D011092:Polyethylene Glycols / Q000008:administration & dosage; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel