title: Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy.
abstract: An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle (dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter randomized phase II study assessed the efficacy and safety of two different approaches: epirubicin 110 mg/m(2) combined with paclitaxel 200 mg/m(2) every 21 days and epirubicin 75 mg/m(2) combined with paclitaxel 175 mg/m(2) every 10 days, both supported with G-CSF. Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade ≥ 3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dose-dense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic) cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194 and 448/1045 mg/m(2), treatment durations were 126 and 61 days, and delivered dose intensities were 36/67 and 51/120 mg/m(2)/week for the dose-escalated and dose-dense arm, respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months, respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time, but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The value of dose-densification over standard scheduled chemotherapy regimes yet needs to be determined.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, GROW-School of Oncology and Developmental Biology, Maastricht Universitair Medisch Centrum, PO Box 5800, 6202 AZ Maastricht, The Netherlands. roy.lalisang@mumc.nl
authors.forename: R I
authors.initials: RI
authors.lastname: Lalisang
authors.forename: F L G
authors.initials: FL
authors.lastname: Erdkamp
authors.forename: C J
authors.initials: CJ
authors.lastname: Rodenburg
authors.forename: C T A M
authors.initials: CT
authors.lastname: Knibbeler-van Rossum
authors.forename: J W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: A
authors.initials: A
authors.lastname: van Bochove
authors.forename: P H Th J
authors.initials: PH
authors.lastname: Slee
authors.forename: E E
authors.initials: EE
authors.lastname: Voest
authors.forename: J A
authors.initials: JA
authors.lastname: Wils
authors.forename: J
authors.initials: J
authors.lastname: Wals
authors.forename: O J L
authors.initials: OJ
authors.lastname: Loosveld
authors.forename: A E M
authors.initials: AE
authors.lastname: Smals
authors.forename: G H
authors.initials: GH
authors.lastname: Blijham
authors.forename: V C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.forename: H C
authors.initials: HC
authors.lastname: Schouten
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D017239:Paclitaxel