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CMF regimen

Abstract: Randomized trial to compare the efficacy and toxicity of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with methotrexate mitoxantrone (MM) in advanced carcinoma of the breast.

One hundred and sixteen patients with locally advanced or metastatic breast cancer were randomized to receive CMF (cyclophosphamide 600 mg m-2 day 1 and 8 i.v., 5-fluorouracil 600 mg m-2 day 1 and 8 i.v.,, methotrexate 40 mg m-2 day 1 and 8 i.v., monthly for 6 cycles) or MM (methotrexate 30 mg m-2, mitoxantrone 6.5 mg m-2, both i.v. day 1 3-weekly for 8 cycles) as first line treatment with chemotherapy. Objective responses occurred in 17 patients out of 58 (29%) who received CMF and nine out of 58 (15%) who received MM; 95% confidence interval for difference in response rates (-1%-29%), P = 0.07. No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged. There was, however, significantly reduced haematological toxicity (P < 0.001) and alopecia (P < 0.001) and fewer dose reductions and delays in patients randomized to MM. No statistically significant differences were seen between the two regimes in terms of quality of life (QOL). However, some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment. Despite the fact that results surrounding response rates and time to progression did not reach statistical significance, their possible compatibility with an improved outcome on CMF treatment must be borne in mind. However, MM is a well-tolerated regimen with fewer side-effects than CMF, which with careful patient management and follow-up, therefore, may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly.

References
C Harper-Wynne, J English, L Meyer, M Bower, C Archer, H D Sinnett, C Lowdell and R C Coombes. Randomized trial to compare the efficacy and toxicity of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with methotrexate mitoxantrone (MM) in advanced carcinoma of the breast.  British Journal of Cancer (1999) 81, 316-322.

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Regimen

Cyclophosphamide....... 600 mg / M2 IV days 1, 8
Methotrexate....... 40 mg / M2 IV days 1, 8
5 - FU....... 600 mg / M2 IV days 1, 8
FREQUENCY.......every 28 days.

     
  Summary CMF d28 regimen vs MM in metastatic breast cancer
  Objective Response rate 29% vs. 15%
  Overall survival No difference
  Time to progression No difference
  Toxicity Significantly reduced haematological toxicity and alopecia and fewer dose reductions and delays in patients randomized to MM.
     
   

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Article reviewed by:

Dr. Tamer Fouad, M.D.

 

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