Duration of adjuvant chemotherapy for breast cancer: A joint analysis of two randomised trials investigating three versus six courses of CMF

Marco Colleoni, H. J. Litman, M. Castiglione-Gertsch, W. Sauerbrei, R. D. Gelber, M. Bonetti, A. S. Coates, M. Schumacher, G. Bastert, C. M. Rudenstam, C. Schmoor, J. Lindtner, J. Collins, B. Thürlimann, S. B. Holmberg, D. Crivellari, C. Beyerle, R. L A Neumann, A. Goldhirsch

Research output: Contribution to journalArticle

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Abstract

Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive 'classical' cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (±s.e.) were 54 ± 2% for three cycles and 55 ± 2% for six cycles (n=1024; risk ratio (risk ratio: CMF × 3/CMF × 6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation.

Original languageEnglish
Pages (from-to)1705-1714
Number of pages10
JournalBritish Journal of Cancer
Volume86
Issue number11
DOIs
Publication statusPublished - Jun 5 2002

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Adjuvant Chemotherapy
Methotrexate
Fluorouracil
Cyclophosphamide
Breast Neoplasms
Estrogen Receptors
Odds Ratio
Confidence Intervals
Neoplasms
Drug Therapy
Tamoxifen
Combination Drug Therapy
Gonadotropin-Releasing Hormone
Disease-Free Survival
Regression Analysis
Clinical Trials
Survival
Therapeutics

Keywords

  • Breast cancer
  • Chemotherapy duration
  • Cyclophosphamide, methotrexate and fluorouracil (CMF)
  • Predictive factors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Duration of adjuvant chemotherapy for breast cancer : A joint analysis of two randomised trials investigating three versus six courses of CMF. / Colleoni, Marco; Litman, H. J.; Castiglione-Gertsch, M.; Sauerbrei, W.; Gelber, R. D.; Bonetti, M.; Coates, A. S.; Schumacher, M.; Bastert, G.; Rudenstam, C. M.; Schmoor, C.; Lindtner, J.; Collins, J.; Thürlimann, B.; Holmberg, S. B.; Crivellari, D.; Beyerle, C.; Neumann, R. L A; Goldhirsch, A.

In: British Journal of Cancer, Vol. 86, No. 11, 05.06.2002, p. 1705-1714.

Research output: Contribution to journalArticle

Colleoni, M, Litman, HJ, Castiglione-Gertsch, M, Sauerbrei, W, Gelber, RD, Bonetti, M, Coates, AS, Schumacher, M, Bastert, G, Rudenstam, CM, Schmoor, C, Lindtner, J, Collins, J, Thürlimann, B, Holmberg, SB, Crivellari, D, Beyerle, C, Neumann, RLA & Goldhirsch, A 2002, 'Duration of adjuvant chemotherapy for breast cancer: A joint analysis of two randomised trials investigating three versus six courses of CMF', British Journal of Cancer, vol. 86, no. 11, pp. 1705-1714. https://doi.org/10.1038/sj.bjc.6600334
Colleoni, Marco ; Litman, H. J. ; Castiglione-Gertsch, M. ; Sauerbrei, W. ; Gelber, R. D. ; Bonetti, M. ; Coates, A. S. ; Schumacher, M. ; Bastert, G. ; Rudenstam, C. M. ; Schmoor, C. ; Lindtner, J. ; Collins, J. ; Thürlimann, B. ; Holmberg, S. B. ; Crivellari, D. ; Beyerle, C. ; Neumann, R. L A ; Goldhirsch, A. / Duration of adjuvant chemotherapy for breast cancer : A joint analysis of two randomised trials investigating three versus six courses of CMF. In: British Journal of Cancer. 2002 ; Vol. 86, No. 11. pp. 1705-1714.
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T1 - Duration of adjuvant chemotherapy for breast cancer

T2 - A joint analysis of two randomised trials investigating three versus six courses of CMF

AU - Colleoni, Marco

AU - Litman, H. J.

AU - Castiglione-Gertsch, M.

AU - Sauerbrei, W.

AU - Gelber, R. D.

AU - Bonetti, M.

AU - Coates, A. S.

AU - Schumacher, M.

AU - Bastert, G.

AU - Rudenstam, C. M.

AU - Schmoor, C.

AU - Lindtner, J.

AU - Collins, J.

AU - Thürlimann, B.

AU - Holmberg, S. B.

AU - Crivellari, D.

AU - Beyerle, C.

AU - Neumann, R. L A

AU - Goldhirsch, A.

PY - 2002/6/5

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N2 - Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive 'classical' cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (±s.e.) were 54 ± 2% for three cycles and 55 ± 2% for six cycles (n=1024; risk ratio (risk ratio: CMF × 3/CMF × 6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation.

AB - Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive 'classical' cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (±s.e.) were 54 ± 2% for three cycles and 55 ± 2% for six cycles (n=1024; risk ratio (risk ratio: CMF × 3/CMF × 6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation.

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