Multiple cycles of high-dose doxorubicin and cyclophosphamide with G- CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer

A. H. Honkoop, E. Van Der Wall, N. Feller, G. J. Schuurhuis, W. J F Van Der Vijgh, E. Boven, C. J. Van Groeningen, G. Giaccone, K. Hoekman, J. B. Vermorken, J. Wagstaff, H. M. Pinedo

Research output: Contribution to journalArticle

Abstract

Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. Patients and methods: For mobilisation of PBPC, G-CSF 15 μg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose- limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%-97%), with 22% (95% CI: 3%-41%) complete responses. Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.

Original languageEnglish (US)
Pages (from-to)957-962
Number of pages6
JournalAnnals of Oncology
Volume8
Issue number10
DOIs
StatePublished - Oct 1997
Externally publishedYes

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Granulocyte Colony-Stimulating Factor
Doxorubicin
Cyclophosphamide
Blood Cells
Stem Cells
Breast Neoplasms
Mucositis
Cystitis
Drug Therapy
Confidence Intervals
Granulocyte-Macrophage Colony-Stimulating Factor
Therapeutics
Pharmaceutical Preparations

Keywords

  • Breast cancer
  • High-dose chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Multiple cycles of high-dose doxorubicin and cyclophosphamide with G- CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer. / Honkoop, A. H.; Van Der Wall, E.; Feller, N.; Schuurhuis, G. J.; Van Der Vijgh, W. J F; Boven, E.; Van Groeningen, C. J.; Giaccone, G.; Hoekman, K.; Vermorken, J. B.; Wagstaff, J.; Pinedo, H. M.

In: Annals of Oncology, Vol. 8, No. 10, 10.1997, p. 957-962.

Research output: Contribution to journalArticle

Honkoop, AH, Van Der Wall, E, Feller, N, Schuurhuis, GJ, Van Der Vijgh, WJF, Boven, E, Van Groeningen, CJ, Giaccone, G, Hoekman, K, Vermorken, JB, Wagstaff, J & Pinedo, HM 1997, 'Multiple cycles of high-dose doxorubicin and cyclophosphamide with G- CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer', Annals of Oncology, vol. 8, no. 10, pp. 957-962. https://doi.org/10.1023/A:1008259518263
Honkoop, A. H. ; Van Der Wall, E. ; Feller, N. ; Schuurhuis, G. J. ; Van Der Vijgh, W. J F ; Boven, E. ; Van Groeningen, C. J. ; Giaccone, G. ; Hoekman, K. ; Vermorken, J. B. ; Wagstaff, J. ; Pinedo, H. M. / Multiple cycles of high-dose doxorubicin and cyclophosphamide with G- CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer. In: Annals of Oncology. 1997 ; Vol. 8, No. 10. pp. 957-962.
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abstract = "Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. Patients and methods: For mobilisation of PBPC, G-CSF 15 μg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47{\%}) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose- limiting toxicity. The overall response rate was 78{\%} (95{\%} confidence interval (95{\%} CI): 57{\%}-97{\%}), with 22{\%} (95{\%} CI: 3{\%}-41{\%}) complete responses. Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.",
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T1 - Multiple cycles of high-dose doxorubicin and cyclophosphamide with G- CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer

AU - Honkoop, A. H.

AU - Van Der Wall, E.

AU - Feller, N.

AU - Schuurhuis, G. J.

AU - Van Der Vijgh, W. J F

AU - Boven, E.

AU - Van Groeningen, C. J.

AU - Giaccone, G.

AU - Hoekman, K.

AU - Vermorken, J. B.

AU - Wagstaff, J.

AU - Pinedo, H. M.

PY - 1997/10

Y1 - 1997/10

N2 - Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. Patients and methods: For mobilisation of PBPC, G-CSF 15 μg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose- limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%-97%), with 22% (95% CI: 3%-41%) complete responses. Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.

AB - Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. Patients and methods: For mobilisation of PBPC, G-CSF 15 μg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose- limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%-97%), with 22% (95% CI: 3%-41%) complete responses. Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.

KW - Breast cancer

KW - High-dose chemotherapy

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