title: Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.
abstract: The aim of this phase II study was to determine the feasibility of using two (tandem) courses of high-dose alkylating agents with bone marrow or peripheral blood progenitor cell support in women with stage IV breast cancer. Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II trial of high-dose cyclophosphamide 7500 mg/m2 and thiotepa 675 mg/m2 (C+T) followed within 180 days by high-dose melphalan (M) 140 mg/m2. Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic progenitor cells were used to support high-dose C+T and high-dose M. Twenty-seven women were enrolled in this trial. The median age was 45 years (range 32-56). The median PS was 0 and all patients had achieved either a CR (4/27, 15%) or PR (23/27, 85%) to conventional chemotherapy. All 27 women underwent high dose C+T. The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infectious complications. Following C+T, the median time to hematologic recovery for neutrophils (ANC > 500 cells/mu 1) was 12 days and for platelets (>20 000 cell/mu 1), 23 days. Following C+T, 18 of 22 patients received high dose M; the predominant toxicities were nausea, vomiting (70%), and mucositis (91%). The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days. The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR* (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%). With median follow-up of 24 months, the actuarial freedom from relapse or treatment failure is 56% at 24 months. At 30 months 56% of patients are alive. For patients who achieve a CR or PR* the actuarial freedom from relapse or treatment failure at 24 months is 88%. In women with stage IV breast cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free survival.
authors.affiliation: Department of Medicine, Lutheran General Hospital, Park Ridge, IL 60068-1, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Bitran
authors.forename: B
authors.initials: B
authors.lastname: Samuels
authors.forename: L
authors.initials: L
authors.lastname: Klein
authors.forename: S
authors.initials: S
authors.lastname: Hanauer
authors.forename: L
authors.initials: L
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Martinec
authors.forename: E
authors.initials: E
authors.lastname: Harris
authors.forename: J
authors.initials: J
authors.lastname: Kempler
authors.forename: W
authors.initials: W
authors.lastname: White
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007239:Infections / Q000209:etiology; D007958:Leukocyte Count; D015993:Life Tables; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010166:Palliative Care; D012074:Remission Induction; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D013852:Thiotepa; D008558:Melphalan