title: Four-cycle high-dose therapy with hematopoietic support for metastatic breast cancer: no improvement in outcomes compared with single-course high-dose therapy.
abstract: Multiple-cycle high-dose therapy with autologous hematopoietic progenitor cell (AHPC) support has been used to deliver dose-intensive therapy. We have used this approach as well as single-cycle high-dose therapy in treating patients with metastatic breast cancer. We present the outcomes of multiple-cycle high-dose therapies and compare them with those resulting from single-course high-dose therapies performed at a single institution. Fifty-five patients received 4 cycles of intensive chemotherapy with AHPC support. Three multicycle regimens were sequentially applied. Twenty patients were enrolled to receive 4 cycles of high-dose mitoxantrone, thiotepa, and cyclophosphamide. Nineteen subsequent patients received this regimen modified by the incorporation of paclitaxel. Sixteen patients received 2 cycles of high-dose melphalan, thiotepa, and paclitaxel and 2 cycles of mitoxantrone, thiotepa, and paclitaxel. The results of all 3 multiple-cycle therapies are compared with those of 55 contemporaneous patients with metastatic breast cancer who received a single course of high-dose cyclophosphamide and thiotepa or cyclophosphamide, cisplatin, and BCNU (carmustine) with hematopoietic cell rescue. Multiple-cycle therapy was associated with more infectious complications, increased transfusion requirements, and increased hospital admissions. However, there were no significant differences in outcomes between the groups. For 55 patients who received multiple-cycle therapy, the actuarial 3-year overall survival rate was 36% (95% confidence interval [CI] 23%-49%); freedom from progression and event-free survival were both 15% (CI 5%-25%). The median time to disease progression and median survival were 1.0 and 1.6 years, respectively. For the 55 patients who underwent a single course of high-dose therapy, the 3-year overall survival was also 36% (CI 18%-54%), whereas freedom from progression and event-free survival were both 19% (CI 7%-31%). The median time to progression and median survival were 0.8 and 2.2 years, respectively. Within the constraints of this patient population, the outcomes of 4 cycles of high-dose therapy with AHPC support were not superior to those resulting from single courses of high-dose therapy in the treatment of patients with metastatic breast cancer.
authors.affiliation: Department of Medicine, Stanford University Medical Center, California 94305, USA. whu@leland.stanford.edu
authors.forename: W W
authors.initials: WW
authors.lastname: Hu
authors.forename: R S
authors.initials: RS
authors.lastname: Negrin
authors.forename: K
authors.initials: K
authors.lastname: Stockerl-Goldstein
authors.forename: L J
authors.initials: LJ
authors.lastname: Johnston
authors.forename: J A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: R M
authors.initials: RM
authors.lastname: Wong
authors.forename: N J
authors.initials: NJ
authors.lastname: Chao
authors.forename: G D
authors.initials: GD
authors.lastname: Long
authors.forename: R H
authors.initials: RH
authors.lastname: Feiner
authors.forename: K G
authors.initials: KG
authors.lastname: Blume
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use* / Q000633:toxicity; D001803:Blood Transfusion; D001943:Breast Neoplasms / Q000556:secondary / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use / Q000633:toxicity; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007239:Infections / Q000209:etiology; D008558:Melphalan / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use / Q000633:toxicity; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity; D015996:Survival Rate; D013852:Thiotepa / Q000627:therapeutic use / Q000633:toxicity; D013997:Time Factors; D014182:Transplantation, Autologous / Q000009:adverse effects
chemical_list: D000277:Adjuvants, Pharmaceutic; D003520:Cyclophosphamide; D013852:Thiotepa; D008942:Mitoxantrone; D017239:Paclitaxel; D002945:Cisplatin; D008558:Melphalan; D002330:Carmustine