title: High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome.
abstract: We assessed the feasibility and pharmacokinetics of high-dose infusional paclitaxel in combination with doxorubicin, cyclophosphamide, and peripheral blood progenitor cell rescue. Between October 1995 and June 1998, 63 patients with high-risk primary [stage II with >or= 10 axillary nodes involved, stage IIIA or stage IIIB inflammatory carcinoma (n = 53)] or with stage IV responsive breast cancer (n = 10) received paclitaxel 150-775 mg/m(2)infused over 24 hours, doxorubicin 165 mg/m(2)as a continuous infusion over 96 hours, and cyclophosphamide 100 mg kg(-1). There were no treatment-related deaths. Dose-limiting toxicity was reversible, predominantly sensory neuropathy following administration of paclitaxel at the 775 mg/m(2) dose level. Paclitaxel pharmacokinetics were non-linear at higher dose levels; higher paclitaxel dose level, AUC, and peak concentrations were associated with increased incidence of paraesthesias. No correlation between stomatitis, haematopoietic toxicities, and paclitaxel dose or pharmacokinetics was found. Kaplan-Meier estimates of 30-month event-free and overall survival for patients with primary breast carcinoma are 65% (95% CI; 51-83%) and 77% (95% CI; 64-93%). Paclitaxel up to 725 mg/m(2) infused over 24 hours in combination with with doxorubicin 165 mg/m(2) and cyclophosphamide 100 mg kg(-1) is tolerable. A randomized study testing this regimen against high-dose carboplatin, thiotepa and cyclophosphamide (STAMP V) is currently ongoing.
authors.affiliation: Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: J H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: T
authors.initials: T
authors.lastname: Synold
authors.forename: J
authors.initials: J
authors.lastname: Longmate
authors.forename: D
authors.initials: D
authors.lastname: Reardon
authors.forename: W
authors.initials: W
authors.lastname: Chow
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
authors.forename: L A
authors.initials: LA
authors.lastname: Leong
authors.forename: K A
authors.initials: KA
authors.lastname: Margolin
authors.forename: R J
authors.initials: RJ
authors.lastname: Morgan
authors.forename: J W
authors.initials: JW
authors.lastname: Raschko
authors.forename: S I
authors.initials: SI
authors.lastname: Shibata
authors.forename: M L
authors.initials: ML
authors.lastname: Tetef
authors.forename: Y
authors.initials: Y
authors.lastname: Yen
authors.forename: N
authors.initials: N
authors.lastname: Kogut
authors.forename: J
authors.initials: J
authors.lastname: Schriber
authors.forename: J
authors.initials: J
authors.lastname: Alvarnas
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000009:adverse effects* / Q000493:pharmacokinetics; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel