High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer

R. E. Lamar, F. A. Greco, D. H. Johnson, P. B. Murphy, J. D. Hainsworth

Research output: Contribution to journalArticle

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Abstract

Background. The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course. Methods. Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease: 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1 and 2; doxorubicin 45 mg/m2 IV on days 1 and 2; cisplatin 20 mg/m2 IV on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 IV on days 15 and 22; leucovorin 15 mg/m2 IV or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 IV on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin. Results. Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/μl and platelets less than 50,000/μl of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths. Conclusions. This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

Original languageEnglish (US)
Pages (from-to)1842-1848
Number of pages7
JournalCancer
Volume73
Issue number7
StatePublished - 1994

Fingerprint

Breast Neoplasms
Drug Therapy
Doxorubicin
Therapeutics
Methotrexate
Stomatitis
Mucositis
Leucovorin
Proxy
Etoposide
Fluorouracil
Cyclophosphamide
Cisplatin
Mouth
Inpatients
Leukocytes
Blood Platelets
Bone Marrow
Cytokines

Keywords

  • combination chemotherapy
  • high-dose chemotherapy
  • metastatic breast cancer
  • Phase II study

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lamar, R. E., Greco, F. A., Johnson, D. H., Murphy, P. B., & Hainsworth, J. D. (1994). High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer. Cancer, 73(7), 1842-1848.

High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer. / Lamar, R. E.; Greco, F. A.; Johnson, D. H.; Murphy, P. B.; Hainsworth, J. D.

In: Cancer, Vol. 73, No. 7, 1994, p. 1842-1848.

Research output: Contribution to journalArticle

Lamar, RE, Greco, FA, Johnson, DH, Murphy, PB & Hainsworth, JD 1994, 'High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer', Cancer, vol. 73, no. 7, pp. 1842-1848.
Lamar RE, Greco FA, Johnson DH, Murphy PB, Hainsworth JD. High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer. Cancer. 1994;73(7):1842-1848.
Lamar, R. E. ; Greco, F. A. ; Johnson, D. H. ; Murphy, P. B. ; Hainsworth, J. D. / High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer. In: Cancer. 1994 ; Vol. 73, No. 7. pp. 1842-1848.
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abstract = "Background. The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course. Methods. Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease: 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1 and 2; doxorubicin 45 mg/m2 IV on days 1 and 2; cisplatin 20 mg/m2 IV on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 IV on days 15 and 22; leucovorin 15 mg/m2 IV or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 IV on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin. Results. Twenty-nine of 40 patients (73{\%}) had objective response to therapy, with 10 (25{\%}) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/μl and platelets less than 50,000/μl of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10{\%}) had treatment-related deaths. Conclusions. This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15{\%} of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.",
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AU - Lamar, R. E.

AU - Greco, F. A.

AU - Johnson, D. H.

AU - Murphy, P. B.

AU - Hainsworth, J. D.

PY - 1994

Y1 - 1994

N2 - Background. The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course. Methods. Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease: 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1 and 2; doxorubicin 45 mg/m2 IV on days 1 and 2; cisplatin 20 mg/m2 IV on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 IV on days 15 and 22; leucovorin 15 mg/m2 IV or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 IV on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin. Results. Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/μl and platelets less than 50,000/μl of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths. Conclusions. This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

AB - Background. The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course. Methods. Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease: 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1 and 2; doxorubicin 45 mg/m2 IV on days 1 and 2; cisplatin 20 mg/m2 IV on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 IV on days 15 and 22; leucovorin 15 mg/m2 IV or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 IV on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin. Results. Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/μl and platelets less than 50,000/μl of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths. Conclusions. This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

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