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Prospective randomized study of cyclophosphamide, epirubicin, and 5-fluorouracil versus cyclophosphamide, adriamycin, and 5-fluorouracil in advanced or recurrent breast cancer

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Treatment with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF), a widely used, potent regimen is sometimes restricted by the myelotoxicity and myocardiotoxicity of adriamycin (ADR). In a prospective randomized controlled study of patients with advanced or recurrent breast cancer, the efficacy and toxicity of a CEF regimen, in which epirubicin (EPI) was substituted for ADR, was compared with CAF.


138 female patients under 75 years of age who had unresectable or recurrent breast cancer during the period from October, 1989 to September, 1991, were randomized to one of two treatment regimens. The first regimen consisted of cyclophosphamide 100 mg p.o. d1-14, adriamycin 30 mg/mp2 i.v. d1, 8 and 5-fluorouracil 500 mg/mp2 i.v. d1, 8 (CAF). In the second regimen, EPI 30 mg/mp2 i.v. d1, 8 was substituted for ADR (CEF). Both regimens were delivered q4 weeks.


Of 138 patients, 105 (CEF 56, CAF 49) were evaluable for response and survival, and all were evaluable for toxicity (CEF 68, CAF 70). The median course of lots CEF and CAF was 3 cycles. Response rates (complete response plus partial response) with CEF and CAF were 35.7% (20/56) and 36.7% (1 8/49), respectively. Adverse effects were similar in the two groups, but severe leukopenia (CEF 36.8%, CAF 64.3%) and hepatic toxicity (CEF 1.5%, CAF 12.9%) were encountered more frequently with CAF than with CEF. The duration of 50% survival was 135.9 weeks for CEF and 172.1 weeks for CAF (not significant).


At an equal dose of EPI and ADR response rates and survival of the CEF group were similar to those of the CAF group, but adverse effects were fewer in the CEF group.

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Cyclophosphamide, adriamycin, and 5-fluorouracil


Cyclophosphamide, epirubicin, and 5-fluorouracil


Complete response




Estrogen receptor


Progressive disease


Partial response


Progesterone receptor


White blood cell


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Correspondence to Tetsuro Kobayashi or Hiroki Koyama or Takahiro Oka or Tadaki Yasumura or Norimichi Kan or Yuichi Takatsuka or Masakuni Noguchi or Ken Morimoto or Takaichiro Suzuki or Takayoshi Tobe or Takesada Mori.

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Kobayashi, T., Koyama, H., Oka, T. et al. Prospective randomized study of cyclophosphamide, epirubicin, and 5-fluorouracil versus cyclophosphamide, adriamycin, and 5-fluorouracil in advanced or recurrent breast cancer. Breast Cancer 6, 37 (1999). https://doi.org/10.1007/BF02966904

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Key words

  • Breast cancer
  • CAF
  • CEF
  • Response
  • Survival