title: Defining the role of novel high-dose chemotherapy regimens for the treatment of high-risk breast cancer.
abstract: We have explored several novel high-dose combinations in an attempt to increase antitumor activity while decreasing treatment-related toxicity. From October 1989 through June 1997, we performed phase I/II dose-escalation trials exploring novel high-dose regimens including ifosfamide/carboplatin/etoposide, mitoxantrone/thiotepa, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/mitoxantrone/thiotepa. We have also evaluated busulfan/cyclophosphamide and cyclophosphamide/thiotepa/carboplatin in phase II trials. Three hundred ninety-three patients have been treated in these trials and followed for a minimum of 3 months. Event-free survival (including relapses and treatment-related mortality; +/-SE) at 3 years by stage and chemosensitivity is as follows: stage II, four to nine positive nodes (n=16), 52%+/-17%; stage II, greater than nine nodes (n=30), 46%+/-11%; stage III (n=59), 50%+/-8%; inflammatory stage III (n=15), 27%+/-17%; stage IV, anthracycline responsive (n=69), 19%+/-5%; stage IV, anthracycline refractory but responsive to salvage therapy with ifosfamide, carboplatin, and etoposide or paclitaxel (n=53), 12%+/-6%; stage IV, refractory (n=128), 5%+/-2%; and stage IV, not evaluable for response (n=23), 10%+/-8%. Treatment-related mortality was 4% for both phase I and II studies involving stage II breast cancer patients, 5% for stage III breast cancer, 15% for inflammatory breast cancer, and 18% for all stage IV breast cancers, responsive and refractory. We conclude that high-dose therapy for the treatment of high-risk early stage breast cancer or metastatic breast cancer results in durable remissions. Chemosensitivity to induction regimens remains the most important prognostic indicator, although long-term survival has been seen even in patients with highly refractory disease. Further studies are necessary to define optimal high-dose strategies based on stage and chemosensitivity of disease.
authors.affiliation: Division of Bone Marrow Transplantation, University of South Florida, Tampa, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Fields
authors.forename: G J
authors.initials: GJ
authors.lastname: Elfenbein
authors.forename: J B
authors.initials: JB
authors.lastname: Perkins
authors.forename: O F
authors.initials: OF
authors.lastname: Ballester
authors.forename: S C
authors.initials: SC
authors.lastname: Goldstein
authors.forename: J W
authors.initials: JW
authors.lastname: Heimenz
authors.forename: R A
authors.initials: RA
authors.lastname: Saez
authors.forename: D M
authors.initials: DM
authors.lastname: Sullivan
authors.forename: J S
authors.initials: JS
authors.lastname: Partyka
authors.forename: L A
authors.initials: LA
authors.lastname: Kronish
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D043823:Taxoids; D013852:Thiotepa / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D005047:Etoposide; D013852:Thiotepa; D016190:Carboplatin; D008942:Mitoxantrone; D017239:Paclitaxel; D007069:Ifosfamide