title: A phase I and pharmacokinetic study of paclitaxel and epirubicin in advanced cancer.
abstract: The objectives of this phase I trial were to determine the maximally tolerated doses of the combination of epirubicin and paclitaxel with and without G-CSF (granulocyte colony stimulating factor) support and to investigate whether epirubicin pharmacokinetics are altered by paclitaxel. Patients with advanced cancer, performance status 0-2, and a normal left ventricular ejection fraction who had received up to 1 prior chemotherapy regimen were treated with epirubicin followed by a 3-hour infusion of paclitaxel repeated every 3 weeks. Dose levels studied were (paclitaxel/epirubicin) 155/75, 175/75, 175/90, 200/90 mg/m2 without G-CSF and 175/90 mg/m2 with G-CSF. Thirty-five patients were entered and all were assessable for toxicity. The dose-limiting dose level was 175 mg/m2 paclitaxel and 90 mg/m2 epirubicin with limiting toxicities of febrile neutropenia, diarrhea and esophagitis. The addition of G-CSF did not allow escalation of epirubicin. No significant cardiac toxicity was observed. Epirubicin pharmacokinetics were studied during the first 2 cycles in 6 patients, who were randomized to receive 1 cycle with no interval between the completion of the epirubicin and the commencement of the paclitaxel infusion and the other cycle with a 72-hour interval between the drugs. There was no substantial effect of paclitaxel on epirubicin or epirubicinol pharmacokinetics, although there was a marginal increase in glucoronidation. In conclusion, paclitaxel 175 mg/m2 and epirubicin 75 mg/m2 is recommended for phase II and III studies.
authors.affiliation: Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia. drischin@peter-mac.unimelb.edu.au
authors.forename: D
authors.initials: D
authors.lastname: Rischin
authors.forename: L K
authors.initials: LK
authors.lastname: Webster
authors.forename: M J
authors.initials: MJ
authors.lastname: Millward
authors.forename: G C
authors.initials: GC
authors.lastname: Toner
authors.forename: S
authors.initials: S
authors.lastname: Nawaratne
authors.forename: V
authors.initials: V
authors.lastname: Ganju
authors.forename: P
authors.initials: P
authors.lastname: Francis
authors.forename: J F
authors.initials: JF
authors.lastname: Bishop
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D011897:Random Allocation
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D017239:Paclitaxel