title: High-dose chemotherapy (CTM) for breast cancer.
abstract: We designed and implemented a new mitoxantrone-based high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninety-one breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m2), thiotepa (600 mg/m2), and mitoxantrone (24-60 mg/m2)) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA patients with 10 or more involved axillary lymph nodes (n = 80) was 62 +/- 12%. Hormone receptor-positive patients with 10 or more nodes did significantly better than negative patients. The EFS for stage IIIB patients at 5 years was 44 +/- 19%; for stage IV patients at 5 years was 17 +/- 10%. Stage IV patients achieving complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving a partial response. There were six (3%) treatment-related deaths including two due to diffuse alveolar hemorrhage. There were no episodes of delayed interstitial pneumonitis. There were six severe cardiac events in 91 patients (6.6%) but none after instituting mitoxantrone dose-adjustment in the final 100 patients. We conclude that CTM is associated with a low treatment-related mortality and little pulmonary toxicity. CTM produces excellent outcomes in stage II/IIIA patients with 10 or more involved axillary lymph nodes.
authors.affiliation: Division of Hematology/Oncology, The University of California, San Francisco 94143-0324, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Damon
authors.forename: J L
authors.initials: JL
authors.lastname: Wolf
authors.forename: H S
authors.initials: HS
authors.lastname: Rugo
authors.forename: E
authors.initials: E
authors.lastname: Gold
authors.forename: A R
authors.initials: AR
authors.lastname: Zander
authors.forename: M
authors.initials: M
authors.lastname: Cassidy
authors.forename: G
authors.initials: G
authors.lastname: Cecchi
authors.forename: N
authors.initials: N
authors.lastname: Cohen
authors.forename: D
authors.initials: D
authors.lastname: Irwin
authors.forename: M
authors.initials: M
authors.lastname: Tracy
authors.forename: C A
authors.initials: CA
authors.lastname: Ries
authors.forename: C A
authors.initials: CA
authors.lastname: Linker
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D011960:Receptors, Estrogen / Q000502:physiology; D011980:Receptors, Progesterone / Q000502:physiology; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D003520:Cyclophosphamide; D013852:Thiotepa; D008942:Mitoxantrone