Treatment of metastatic breast cancer with a split-course high-dose chemotherapy regimen and autologous bone marrow transplantation

Richard Ghalie, Carol M Richman, Solomon S. Adler, Melody A. Cobleigh, Allen D. Korenblit, Sharon D. Manson, Bruce C. McLeod, Samuel G. Taylor IV, Leonard A. Valentino, Janet Wolter, Herbert Kaizer

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Abstract

Purpose: We investigated the role of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) as the initial systemic treatment in patients with hormone-unresponsive metastatic breast cancer. We studied a regimen involving a split-course schedule using sequential administration of two pairs of alkylating agents separated by 5 days of rest. The rest period was intended to provide time for recovery from the treatment-immediate adverse effects, thereby allowing further dose escalation. Patients and Methods: The treatment consisted of thiotepa 225 to 300 mg/m2/d (days-11 to -9), cisplatin 50 to 100 mg/m2/d (days-11 and -3), and cyclophosphamide 60 mg/kg/d (days-3 and -2). Dose escalation was performed in the initial 15 patients before reaching dose-limiting toxicities. When feasible, responding patients received posttransplant irradiation to sites of residual or prior bulky disease. Patients with bone marrow or CNS involvement, prior pelvic irradiation, or age greater than 55 years were excluded. Results: Thirty- nine patients with measurable or assessable tumor were enrolled: 23 with visceral metastases, 11 with only soft tissue disease, and five with skeletal involvement. Twenty-five patients had received no chemotherapy for metastatic disease before transplantation. The dose-limiting toxicities of this therapy were renal and gastrointestinal. Six patients died from complications: four of a fungal infection and two of hemorrhage. A complete response was achieved in 14 patients (36%), three of whom are free of disease at 79+, 55+, and 40+ months after transplantation. Ten of 25 patients not treated with standard- dose chemotherapy for metastatic disease achieved a complete response (40%). The three patients in continuous remission were in the untreated relapse group. Conclusion: This single high-dose treatment achieved a relatively high complete response rate in patients with metastatic breast cancer and may have cured some of them. On the other hand, the split-course dose schedule as tested here did not permit significant dose-intensification.

Original languageEnglish (US)
Pages (from-to)342-346
Number of pages5
JournalJournal of Clinical Oncology
Volume12
Issue number2
StatePublished - Feb 1994
Externally publishedYes

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Autologous Transplantation
Bone Marrow Transplantation
Breast Neoplasms
Drug Therapy
Therapeutics
Appointments and Schedules
Transplantation
Thiotepa
Mycoses
Alkylating Agents
Cyclophosphamide
Cisplatin
Bone Marrow
Hormones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ghalie, R., Richman, C. M., Adler, S. S., Cobleigh, M. A., Korenblit, A. D., Manson, S. D., ... Kaizer, H. (1994). Treatment of metastatic breast cancer with a split-course high-dose chemotherapy regimen and autologous bone marrow transplantation. Journal of Clinical Oncology, 12(2), 342-346.

Treatment of metastatic breast cancer with a split-course high-dose chemotherapy regimen and autologous bone marrow transplantation. / Ghalie, Richard; Richman, Carol M; Adler, Solomon S.; Cobleigh, Melody A.; Korenblit, Allen D.; Manson, Sharon D.; McLeod, Bruce C.; Taylor IV, Samuel G.; Valentino, Leonard A.; Wolter, Janet; Kaizer, Herbert.

In: Journal of Clinical Oncology, Vol. 12, No. 2, 02.1994, p. 342-346.

Research output: Contribution to journalArticle

Ghalie, R, Richman, CM, Adler, SS, Cobleigh, MA, Korenblit, AD, Manson, SD, McLeod, BC, Taylor IV, SG, Valentino, LA, Wolter, J & Kaizer, H 1994, 'Treatment of metastatic breast cancer with a split-course high-dose chemotherapy regimen and autologous bone marrow transplantation', Journal of Clinical Oncology, vol. 12, no. 2, pp. 342-346.
Ghalie, Richard ; Richman, Carol M ; Adler, Solomon S. ; Cobleigh, Melody A. ; Korenblit, Allen D. ; Manson, Sharon D. ; McLeod, Bruce C. ; Taylor IV, Samuel G. ; Valentino, Leonard A. ; Wolter, Janet ; Kaizer, Herbert. / Treatment of metastatic breast cancer with a split-course high-dose chemotherapy regimen and autologous bone marrow transplantation. In: Journal of Clinical Oncology. 1994 ; Vol. 12, No. 2. pp. 342-346.
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abstract = "Purpose: We investigated the role of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) as the initial systemic treatment in patients with hormone-unresponsive metastatic breast cancer. We studied a regimen involving a split-course schedule using sequential administration of two pairs of alkylating agents separated by 5 days of rest. The rest period was intended to provide time for recovery from the treatment-immediate adverse effects, thereby allowing further dose escalation. Patients and Methods: The treatment consisted of thiotepa 225 to 300 mg/m2/d (days-11 to -9), cisplatin 50 to 100 mg/m2/d (days-11 and -3), and cyclophosphamide 60 mg/kg/d (days-3 and -2). Dose escalation was performed in the initial 15 patients before reaching dose-limiting toxicities. When feasible, responding patients received posttransplant irradiation to sites of residual or prior bulky disease. Patients with bone marrow or CNS involvement, prior pelvic irradiation, or age greater than 55 years were excluded. Results: Thirty- nine patients with measurable or assessable tumor were enrolled: 23 with visceral metastases, 11 with only soft tissue disease, and five with skeletal involvement. Twenty-five patients had received no chemotherapy for metastatic disease before transplantation. The dose-limiting toxicities of this therapy were renal and gastrointestinal. Six patients died from complications: four of a fungal infection and two of hemorrhage. A complete response was achieved in 14 patients (36{\%}), three of whom are free of disease at 79+, 55+, and 40+ months after transplantation. Ten of 25 patients not treated with standard- dose chemotherapy for metastatic disease achieved a complete response (40{\%}). The three patients in continuous remission were in the untreated relapse group. Conclusion: This single high-dose treatment achieved a relatively high complete response rate in patients with metastatic breast cancer and may have cured some of them. On the other hand, the split-course dose schedule as tested here did not permit significant dose-intensification.",
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AU - Richman, Carol M

AU - Adler, Solomon S.

AU - Cobleigh, Melody A.

AU - Korenblit, Allen D.

AU - Manson, Sharon D.

AU - McLeod, Bruce C.

AU - Taylor IV, Samuel G.

AU - Valentino, Leonard A.

AU - Wolter, Janet

AU - Kaizer, Herbert

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N2 - Purpose: We investigated the role of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) as the initial systemic treatment in patients with hormone-unresponsive metastatic breast cancer. We studied a regimen involving a split-course schedule using sequential administration of two pairs of alkylating agents separated by 5 days of rest. The rest period was intended to provide time for recovery from the treatment-immediate adverse effects, thereby allowing further dose escalation. Patients and Methods: The treatment consisted of thiotepa 225 to 300 mg/m2/d (days-11 to -9), cisplatin 50 to 100 mg/m2/d (days-11 and -3), and cyclophosphamide 60 mg/kg/d (days-3 and -2). Dose escalation was performed in the initial 15 patients before reaching dose-limiting toxicities. When feasible, responding patients received posttransplant irradiation to sites of residual or prior bulky disease. Patients with bone marrow or CNS involvement, prior pelvic irradiation, or age greater than 55 years were excluded. Results: Thirty- nine patients with measurable or assessable tumor were enrolled: 23 with visceral metastases, 11 with only soft tissue disease, and five with skeletal involvement. Twenty-five patients had received no chemotherapy for metastatic disease before transplantation. The dose-limiting toxicities of this therapy were renal and gastrointestinal. Six patients died from complications: four of a fungal infection and two of hemorrhage. A complete response was achieved in 14 patients (36%), three of whom are free of disease at 79+, 55+, and 40+ months after transplantation. Ten of 25 patients not treated with standard- dose chemotherapy for metastatic disease achieved a complete response (40%). The three patients in continuous remission were in the untreated relapse group. Conclusion: This single high-dose treatment achieved a relatively high complete response rate in patients with metastatic breast cancer and may have cured some of them. On the other hand, the split-course dose schedule as tested here did not permit significant dose-intensification.

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