TY - JOUR
T1 - High-dose chemotherapy with reinfusion of purged autologous bone marrow following dose-intense induction as initial therapy for metastatic breast cancer
AU - Kennedy, M. John
AU - Beveridge, Roy A.
AU - Rowley, Scott D.
AU - Gordon, Gary B.
AU - Abeloff, Martin D.
AU - Davidson, Nancy E.
N1 - Funding Information:
Received December 17, 1990; revised March 18, 1991; accepted April 2, 1991. N. E. Davidson was supported in part by American Cancer Society Clinical Oncology Career Development Award 90-128, the Susan Komen Foundation, and a Merck Clinician Scientist Award from The Johns Hopkins School of Medicine. G. B. Gordon was the recipient of a W. M. Keck Foundation Clinician Scientist Award from The Johns Hopkins School of Medicine. M. J. Kennedy, S. D. Rowley, G. B. Gordon, M. D. Abeloff, N. E. Davidson, The Johns Hopkins Oncology Center, Baltimore, Md. R. A. Beveridge, Fairfax Hospital, Fairfax, Va. We thank the medical oncologists who referred patients for this study and the medical and nursing staff of Oncology 3N and 3A who provided expert care. We are grateful for the meticulous data collection performed by Dorothy Damron and Bonnie Shelton and the excellent secretarial skills of Tammy Deitrich. We also thank Richard Jones, Rein Saral, and George Santos for their consistent support and advice. Correspondence to: M. John Kennedy, MB MRCPI, Oncology 137, The Johns Hopkins Oncology Center, 600 N. Wolfe St, Baltimore, MD 21205.
PY - 1991/7/3
Y1 - 1991/7/3
N2 - We assessed the toxicity and efficacy of high-dose chemotherapy consolidation with reinfusion of purged autologous bone marrow in women with metastatic breast cancer responding to a dose-intense outpatient regimen. Thirty women with hormone-unresponsive metastatic breast cancer, previously untreated with adjuvant doxorubicin or with any chemotherapy for metastatic disease, were treated with cyclophosphamide, methotrexate, doxorubicin, fluorouracil, vincristine, and leucovorin for 16 weeks. Twenty-four patients responded to therapy; 8 showed a complete response, and 16 showed a partial response. These patients proceeded to the next phase of the protocol, ie, marrow harvest and treatment with 6000 mg/m2 cyclophosphamide and 800 mg/m2 thiotepa given over 4 days. Harvested marrow was purged with 100 μg/mL 4-hydroperoxycyclophosphamide, and all patients engrafted satisfactorily. The predominant side effects were myelosuppressive and gastrointestinal, and there were no deaths from toxic effects. Three of the 16 patients who showed a partial response after the outpatient phase of treatment achieved a complete response after high-dose therapy. The partial response seen in two more patients converted to a complete response at all sites except bone. The median time to disease progression for all patients in this study was 13 months, and the median survival was 22 months. Four of the original 30 patients remained without disease progression a median of 27 months from entry into the study. This study indicates that this dose-intense regimen can be safely administered, even with the use of purged marrow, with an acceptable toxicity profile. This approach results in a high response rate in women with metastatic breast cancer and could form the basis for a regimen to be tested in the high-risk adjuvant setting. [J Natl Cancer Inst 83: 920-926, 1991]
AB - We assessed the toxicity and efficacy of high-dose chemotherapy consolidation with reinfusion of purged autologous bone marrow in women with metastatic breast cancer responding to a dose-intense outpatient regimen. Thirty women with hormone-unresponsive metastatic breast cancer, previously untreated with adjuvant doxorubicin or with any chemotherapy for metastatic disease, were treated with cyclophosphamide, methotrexate, doxorubicin, fluorouracil, vincristine, and leucovorin for 16 weeks. Twenty-four patients responded to therapy; 8 showed a complete response, and 16 showed a partial response. These patients proceeded to the next phase of the protocol, ie, marrow harvest and treatment with 6000 mg/m2 cyclophosphamide and 800 mg/m2 thiotepa given over 4 days. Harvested marrow was purged with 100 μg/mL 4-hydroperoxycyclophosphamide, and all patients engrafted satisfactorily. The predominant side effects were myelosuppressive and gastrointestinal, and there were no deaths from toxic effects. Three of the 16 patients who showed a partial response after the outpatient phase of treatment achieved a complete response after high-dose therapy. The partial response seen in two more patients converted to a complete response at all sites except bone. The median time to disease progression for all patients in this study was 13 months, and the median survival was 22 months. Four of the original 30 patients remained without disease progression a median of 27 months from entry into the study. This study indicates that this dose-intense regimen can be safely administered, even with the use of purged marrow, with an acceptable toxicity profile. This approach results in a high response rate in women with metastatic breast cancer and could form the basis for a regimen to be tested in the high-risk adjuvant setting. [J Natl Cancer Inst 83: 920-926, 1991]
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U2 - 10.1093/jnci/83.13.920
DO - 10.1093/jnci/83.13.920
M3 - Article
C2 - 1906111
AN - SCOPUS:0025848020
SN - 0027-8874
VL - 83
SP - 920
EP - 926
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 13
ER -