title: High-dose chemotherapy with autologous peripheral blood progenitor cell support for primary breast cancer in patients with 4-9 involved axillary lymph nodes.
abstract: Breast cancer patients with more than three involved axillary lymph have a high likelihood of relapse after adjuvant therapy. Early results of administration of high-dose chemotherapy (HDCT) and autologous peripheral blood progenitor cells (PBPC) to patients with primary breast cancer and > or = 10 involved axillary nodes have been encouraging. We performed a multicenter trial to determine whether HDCT could be safely administered to patients with primary breast cancer involving 4-9 axillary lymph nodes. Fifty-four patients with stage II or III breast cancer and 4-9 involved axillary lymph nodes received doxorubicin-based induction chemotherapy, followed by high-dose cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (450 mg/m2) and PBPC mobilized by sargramostim (GM-CSF) or filgrastim (G-CSF). After completion of HDCT, patients received radiation therapy to the chest wall or involved breast, plus tamoxifen. Survival and disease-free survival, time to engraftment, and charges associated with HDCT were determined. Plasma concentrations of BCNU were determined and plasma AUC(BCNU) was calculated. Fifty-four patients were evaluable for survival and relapse-free survival. Fifty-two patients received HDCT with PBPC support and were evaluable for toxicity. Fifteen patients (29%) developed late pulmonary drug toxicity, which resolved with a 10-week course of corticosteroids in all but one affected patient, who subsequently died of pulmonary toxicity. Ten patients relapsed a median of 426 days (range 86-1117 days) after the start of induction chemotherapy, seven of whom have died. Forty-three patients are alive and breast cancer-free at a median of 947 days (range 661-1730 days) after the start of therapy, including one patient who developed myelodysplastic syndrome 809 days after the start of HDCT. Actuarial 4-year survival and disease-free survival from the start of treatment are 84 and 71%, respectively. Mean plasma AUC(BCNU) was 400 (range 82-1255) microgxmin/ml and was not statistically different from that measured in historical controls who received 600 mg/m2 of BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125845 for the first four patients to $77126 for the final seven patients. We conclude that HDCT with autologous PBPC can be administered with acceptable safety to patients with primary breast cancer involving 4-9 axillary lymph nodes. An ongoing, prospective randomized trial is evaluating the efficacy of HDCT for this patient group.
authors.affiliation: Bone Marrow Transplant Programs of University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Bearman
authors.forename: B A
authors.initials: BA
authors.lastname: Overmoyer
authors.forename: B J
authors.initials: BJ
authors.lastname: Bolwell
authors.forename: C W
authors.initials: CW
authors.lastname: Taylor
authors.forename: E J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: P J
authors.initials: PJ
authors.lastname: Cagnoni
authors.forename: B E
authors.initials: BE
authors.lastname: Mechling
authors.forename: B
authors.initials: B
authors.lastname: Ronk
authors.forename: A E
authors.initials: AE
authors.lastname: Barón
authors.forename: M H
authors.initials: MH
authors.lastname: Purdy
authors.forename: M
authors.initials: M
authors.lastname: Ross
authors.forename: R B
authors.initials: RB
authors.lastname: Jones
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D018567:Breast Neoplasms, Male / Q000000981:diagnostic imaging / Q000628:therapy; D002330:Carmustine / Q000008:administration & dosage / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000627:therapeutic use; D013629:Tamoxifen / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D011994:Recombinant Proteins; D013629:Tamoxifen; D016179:Granulocyte Colony-Stimulating Factor; C081222:sargramostim; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D000069585:Filgrastim; D002945:Cisplatin; D002330:Carmustine