title: Cardiac sequelae of doxorubicin and paclitaxel as induction chemotherapy prior to high-dose chemotherapy and peripheral blood progenitor cell transplantation in women with high-risk primary or metastatic breast cancer.
abstract: Doxorubicin plus paclitaxel has been shown to be an active regimen for metastatic breast cancer and is now frequently used as adjuvant therapy for high-risk primary breast cancer. Initial studies reported a higher than expected rate of cardiac toxicity with this regimen. We studied 105 patients with either high-risk primary breast cancer or metastatic breast cancer who were treated with doxorubicin (60 mg/m2) and 3-h infusions of paclitaxel (175 mg/m2) cycled every 3 weeks. Patients received three cycles of chemotherapy for high-risk primary or four cycles for metastatic disease. Patients then proceeded to high-dose chemotherapy (HDC) (STAMP I cyclophosphamide, cisplatin and carmustine) and peripheral blood progenitor cell transplantation (PBPCT). Patients underwent radionuclide multi-gated angiograms (MUGA) before and following induction chemotherapy and following HDC. During induction chemotherapy 40 (38%) of the patients had a reduction in left ventricular ejection fraction (LVEF). Fourteen had a decrease of 20% or greater and two were mildly symptomatic from CHF. There was additional reduction in the LVEF after HDC with a median value for LVEF of 59% (range, 20-78%). During HDC 10 patients developed clinical signs of congestive heart failure (CHF). Five patients responded to diuretic therapy and did not require any additional treatment. Four patients responded to vasodilation and/or digoxin with improvement in cardiac function. A clinically significant decrease in cardiac function was found in a small number of patients after induction chemotherapy and HDC with PBPCT. The majority of the patients tolerated this regimen without problems. Although there was a decline in LVEF as measured by radionuclide MUGA this did not prevent the majority of patients from proceeding with HDC. Bone Marrow Transplantation (2000).
authors.affiliation: Barbara Ann Karmanos Cancer Center, Wayne State University School of Medicine, Division of Hematology and Oncology, Detroit, Michigan, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Klein
authors.forename: P M
authors.initials: PM
authors.lastname: Rey
authors.forename: R D
authors.initials: RD
authors.lastname: Dansey
authors.forename: C
authors.initials: C
authors.lastname: Karanes
authors.forename: W
authors.initials: W
authors.lastname: Du
authors.forename: E
authors.initials: E
authors.lastname: Abella
authors.forename: L
authors.initials: L
authors.lastname: Cassells
authors.forename: C
authors.initials: C
authors.lastname: Hamm
authors.forename: W P
authors.initials: WP
authors.lastname: Peters
authors.forename: R D
authors.initials: RD
authors.lastname: Baynes
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* / Q000532:radiotherapy / Q000628:therapy; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004357:Drug Synergism; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects*; D011878:Radiotherapy / Q000009:adverse effects; D012306:Risk; D013318:Stroke Volume; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000209:etiology
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin; D002330:Carmustine