title: Consolidation with high-dose combination alkylating agents with bone marrow transplantation significantly improves disease-free survival in hormone-insensitive metastatic breast cancer in complete remission compared with intensive standard-dose chemotherapy alone.
abstract: We conducted this study to determine event-free and overall survival among women with hormone-insensitive or hormone-resistant metastatic breast cancer receiving consolidation with high-dose chemotherapy (HDC) and hematopoietic support versus no further chemotherapy after intensive induction chemotherapy. Eligible patients received induction doxorubicin, 5-fluorouracil, and methotrexate (AFM) for 2 to 4 cycles. Women in complete remission were randomized to immediate HDC with cyclophosphamide, cisplatin, and carmustine followed by autologous hematopoietic support or to no further therapy. Patients on the observation arm of therapy were offered salvage HDC at the time of relapse. Partial responders to AFM were offered immediate HDC. A total of 425 patients were enrolled onto the study. The median event-free survival for women randomized to induction therapy alone was 3.8 months, compared with 9.7 months for women who completed HDC (P < .006). Of the patients randomized to observation, 5 (10%) of 51 remain event free, compared with 13 (26%) of 49 patients who underwent immediate HDC (P = .03). Of women converted to a complete response by salvage HDC after a partial response to AFM, overall survival was similar to that in women randomized to immediate HDC. Follow-up is now in excess of 5 years. The 5-year event-free survival is 15% (95% confidence interval, 12%-18%), and the 5-year overall survival is 20% (95% confidence interval, 17%-25%). Immediate HDC after a complete response to AFM produced some durable long-term responses in hormone-insensitive/-resistant metastatic breast cancer. Salvage HDC converted 30% of partial responders to complete responders with similar survivals. The addition of novel targeted therapies to intensive-dose chemotherapy regimens may further improve survival in metastatic breast cancer.
authors.affiliation: Duke University Medical Center, Durham, North Carolina 27710, USA. vrede001@mc.duke.edu
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: David
authors.initials: D
authors.lastname: Coniglio
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Roy B
authors.initials: RB
authors.lastname: Jones
authors.forename: Maureen
authors.initials: M
authors.lastname: Ross
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Atif
authors.initials: A
authors.lastname: Hussein
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.forename: Larry B
authors.initials: LB
authors.lastname: Marks
authors.forename: Colleen
authors.initials: C
authors.lastname: Gilbert
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Affronti
authors.forename: Sarah
authors.initials: S
authors.lastname: Moore
authors.forename: Carolyn
authors.initials: C
authors.lastname: McDonald
authors.forename: William P
authors.initials: WP
authors.lastname: Petros
authors.forename: William P
authors.initials: WP
authors.lastname: Peters
mesh_terms: D000328:Adult; D000477:Alkylating Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000401:mortality; D001943:Breast Neoplasms / Q000401:mortality* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D016879:Salvage Therapy / Q000379:methods / Q000401:mortality; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D000477:Alkylating Agents; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C499413:S100A4 protein, Bos taurus