title: Analysis of dose-response relationships in the setting of high-dose ifosfamide, carboplatin, and etoposide and autologous hematopoietic stem cell transplantation: implications for the treatment of patients with advanced breast cancer.
abstract: Dose intensity appears to play a role in the treatment of breast cancer. Although many reports have been published regarding dose intensity using nonmyeloablative doses, little data have been presented in the setting of high-dose chemotherapy and autologous hematopoietic stem cell transplantation. The results of a retrospective review of a phase I/II trial evaluating the effect of escalating doses of ifosfamide/carboplatin/etoposide on survival of patients with locally advanced and metastatic breast cancer are discussed here. Patients were divided by ifosfamide dose: low dose (6,000 to 14,400 mg/m2) and high dose (17,100 to 24,000 mg/m2). Three-year event-free survival was no different between the two dose groups in patients with locally advanced disease (71% [low] v 56% [high]). In patients with metastatic disease, however, although the difference did not meet statistical significance, there did appear to be a trend toward improved survival with increased dose intensity (8% [low] v 25% [high]). Our results show that dose intensity may be important in inflammatory and metastatic breast cancer. This trend was seen in both anthracycline-responsive and -refractory patients. While further study of dose intensity in this setting is warranted, dose-intensive high-dose therapy with autologous hematopoietic stem cell transplantation can be considered for patients with advanced breast cancer.
authors.affiliation: Division of Bone Marrow Transplantation, Department of Internal Medicine, University of South Florida at the H. Lee Moffitt Cancer Center, Tampa, 33612, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Perkins
authors.forename: G J
authors.initials: GJ
authors.lastname: Effenbein
authors.forename: K K
authors.initials: KK
authors.lastname: Fields
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000628:therapy; D016190:Carboplatin / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D012189:Retrospective Studies; D015996:Survival Rate; D014182:Transplantation, Autologous
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide