Analysis of the prognostic effects of inclusion in a clinical trial and of myelosuppression on survival after adjuvant chemotherapy for breast carcinoma

Cancer. 2001 Jun 15;91(12):2246-57.


Background: Treatment-related factors that might influence survival after adjuvant treatment for breast carcinoma include treatment as part of a clinical trial, toxicity of treatment, the regimen and schedule used, and dose intensity.

Methods: The authors reviewed the records of 680 patients with breast carcinoma who received adjuvant treatment with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) at Princess Margaret Hospital between 1980-1990. They analyzed the effects on survival of inclusion in a clinical trial (n = 160) and of experiencing Grade 3/4 myelosuppression (according to National Cancer Institute Common Toxicity Criteria) (n = 227, with available data for 584 patients). In an exploratory analysis, the authors examined the effects of the CMF regimen ("classic" CMF [n = 417] vs. intravenous CMF [n = 243]) and of relative dose intensity. Each of these factors was tested in a Cox proportional hazards model with the known prognostic factors of N classification, T classification, estrogen receptor (ER) and progesterone receptor (PR) status, and use of adjuvant hormonal therapy to determine whether they provided additional prognostic information.

Results: In univariate analysis, inclusion in a clinical trial was associated with better survival (P = 0.02) with a nonsignificant trend when corrected for other prognostic factors in a multivariate analysis (hazard ratio [HR] = 0.77; 95% confidence interval [CI], 0.56-1.04). There was a similar trend for patients experiencing myelosuppression (HR = 0.77; 95% CI, 0.59-1.00). In exploratory analysis the use of classic CMF, with higher absolute dose intensity, also was associated with a trend toward improved survival (HR = 0.79; 95% CI, 0.63-1.00).

Conclusions: The results of the current study suffer from the inherent problems of retrospective analysis, but, similar to findings for other disease sites, they suggest that patients included in clinical trials have better outcome. Classic CMF should be used when this regimen is selected for adjuvant treatment, and dose adjustment resulting in moderate myelosuppression should be explored in future clinical trials.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Bone Marrow / physiology*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / therapy*
  • Chemotherapy, Adjuvant*
  • Cisplatin / administration & dosage
  • Clinical Trials as Topic*
  • Combined Modality Therapy
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Lymphatic Metastasis
  • Methotrexate / administration & dosage
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome


  • Cisplatin
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF protocol