Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement

Sjoerd Rodenhuis, Dick J. Richel, Elsken Van Der Wall, Jan H. Schornagel, Joke W. Baars, Caro C E Koning, Johannes L. Peterse, Jacques H. Borger, Willem J. Nooijen, Roel Bakx, Otilia Dalesio, Emiel Rutgers

Research output: Contribution to journalArticle

Abstract

Background. Uncontrolled studies suggest that high-dose chemotherapy is beneficial in patients with breast cancer and multiple metastases to the axillary lymph nodes. Many physicians accept this treatment as standard care. We aimed to assess adjuvant high-dose chemotherapy in breast cancer in a phase II randomised trial. Methods. 97 women aged younger than 60 years, who had breast cancer with extensive axillary-node metastases (confirmed by a tumour-positive infraclavicular lymph-node biopsy), received three courses of up-front chemotherapy (FE120C). This regimen consisted of cyclophosphamide 500 mg/m2, epirubicin 120 mg/m2, and 5-fluorouracil 500 mg/m2 once weekly for 3 weeks. After surgery, stable patients or those who responded to chemotherapy were randomly assigned conventional therapy (fourth course of FE120C, followed by radiation therapy and 2 years of tamoxifen [40 patients]) or high-dose therapy (identical treatment but an additional high-dose regimen and peripheral-blood progenitor-cell [PBPC] support after the fourth FE120C course [41 patients]). This high-dose regimen comprised cyclophosphamide 6 g/m2, thiotepa 480 mg/m2, and carboplatin 1600 mg/m2. The primary endpoint was overall and disease-free survival. All analyses were by intention to treat. Findings. No patients died from toxic effects of chemotherapy. With a median follow-up of 49 (range 21-76) months, the 4-year overall and relapse-free survivals for all 97 patients were 75% and 54% respectively. There was no significant difference in survival between the patients on conventional therapy and those on high-dose therapy. Interpretation. High-dose therapy is associated with substantial cost and acute toxic effects, but also has potentially irreversible long-term effects. Until the benefit of this therapy is substantiated by large-scale phase III trials, high-dose chemotherapy should not be used in the adjuvant treatment of breast cancer, apart from in randomised studies.

Original languageEnglish (US)
Pages (from-to)515-521
Number of pages7
JournalThe Lancet
Volume352
Issue number9127
DOIs
StatePublished - Aug 15 1998
Externally publishedYes

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Stem Cells
Lymph Nodes
Breast Neoplasms
Drug Therapy
Therapeutics
Poisons
Cyclophosphamide
Thiotepa
Neoplasm Metastasis
Epirubicin
Intention to Treat Analysis
Survival
Carboplatin
Tamoxifen
Fluorouracil
Disease-Free Survival
Blood Cells
Radiotherapy
Physicians
Biopsy

ASJC Scopus subject areas

  • Medicine(all)

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Rodenhuis, S., Richel, D. J., Van Der Wall, E., Schornagel, J. H., Baars, J. W., Koning, C. C. E., ... Rutgers, E. (1998). Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. The Lancet, 352(9127), 515-521. https://doi.org/10.1016/S0140-6736(98)01350-6

Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. / Rodenhuis, Sjoerd; Richel, Dick J.; Van Der Wall, Elsken; Schornagel, Jan H.; Baars, Joke W.; Koning, Caro C E; Peterse, Johannes L.; Borger, Jacques H.; Nooijen, Willem J.; Bakx, Roel; Dalesio, Otilia; Rutgers, Emiel.

In: The Lancet, Vol. 352, No. 9127, 15.08.1998, p. 515-521.

Research output: Contribution to journalArticle

Rodenhuis, S, Richel, DJ, Van Der Wall, E, Schornagel, JH, Baars, JW, Koning, CCE, Peterse, JL, Borger, JH, Nooijen, WJ, Bakx, R, Dalesio, O & Rutgers, E 1998, 'Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement', The Lancet, vol. 352, no. 9127, pp. 515-521. https://doi.org/10.1016/S0140-6736(98)01350-6
Rodenhuis, Sjoerd ; Richel, Dick J. ; Van Der Wall, Elsken ; Schornagel, Jan H. ; Baars, Joke W. ; Koning, Caro C E ; Peterse, Johannes L. ; Borger, Jacques H. ; Nooijen, Willem J. ; Bakx, Roel ; Dalesio, Otilia ; Rutgers, Emiel. / Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. In: The Lancet. 1998 ; Vol. 352, No. 9127. pp. 515-521.
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abstract = "Background. Uncontrolled studies suggest that high-dose chemotherapy is beneficial in patients with breast cancer and multiple metastases to the axillary lymph nodes. Many physicians accept this treatment as standard care. We aimed to assess adjuvant high-dose chemotherapy in breast cancer in a phase II randomised trial. Methods. 97 women aged younger than 60 years, who had breast cancer with extensive axillary-node metastases (confirmed by a tumour-positive infraclavicular lymph-node biopsy), received three courses of up-front chemotherapy (FE120C). This regimen consisted of cyclophosphamide 500 mg/m2, epirubicin 120 mg/m2, and 5-fluorouracil 500 mg/m2 once weekly for 3 weeks. After surgery, stable patients or those who responded to chemotherapy were randomly assigned conventional therapy (fourth course of FE120C, followed by radiation therapy and 2 years of tamoxifen [40 patients]) or high-dose therapy (identical treatment but an additional high-dose regimen and peripheral-blood progenitor-cell [PBPC] support after the fourth FE120C course [41 patients]). This high-dose regimen comprised cyclophosphamide 6 g/m2, thiotepa 480 mg/m2, and carboplatin 1600 mg/m2. The primary endpoint was overall and disease-free survival. All analyses were by intention to treat. Findings. No patients died from toxic effects of chemotherapy. With a median follow-up of 49 (range 21-76) months, the 4-year overall and relapse-free survivals for all 97 patients were 75{\%} and 54{\%} respectively. There was no significant difference in survival between the patients on conventional therapy and those on high-dose therapy. Interpretation. High-dose therapy is associated with substantial cost and acute toxic effects, but also has potentially irreversible long-term effects. Until the benefit of this therapy is substantiated by large-scale phase III trials, high-dose chemotherapy should not be used in the adjuvant treatment of breast cancer, apart from in randomised studies.",
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AU - Schornagel, Jan H.

AU - Baars, Joke W.

AU - Koning, Caro C E

AU - Peterse, Johannes L.

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