Less Cycles of CMF (adj chemo)

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

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.

[06/12/2002; British Journal of Cancer]

Ann's NOTE: As patients we need to know that the 'correct' dose schedule for any chemotherapy is unknown. If you suggest that a particular individual needs a specific schedule, that is wholly unexplored.

But this study demonstrates that although CMF has been given for 6 cycles, it is now shown that 3 cycles may be BETTER for women OVER 40 with Estrogen Receptor Positive tumors.

This is very interesting because one of the reasons to approve use of anthracycline chemotherapy, even though it is MUCH more toxic to the heart, was that is was only given for 4 cycles NOT 6 as with CMF.


Discussion: Adj Therapy Postmenopausal Women

JCNI Cancer Spectrum

Editorial:Adjno Chemo Postmeno Lymph-Node Neg

JNCI Cancer Spectrum, 7/02

Sequential Docetaxel: No Benefit in Early Breast Cancer

Lancet 2009; 373: 1681-92. May 2009


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