title: The effect of adjuvant prednisone combined with CMF on patterns of relapse and occurrence of second malignancies in patients with breast cancer. International (Ludwig) Breast Cancer Study Group.
abstract: BACKGROUND
  The addition of low-dose prednisone (p) to the adjuvant regimen of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) allowed patients to receive a larger dose of cytotoxics when compared with those on CMF alone. However, disease-free survival and overall survival were similar for the two groups. To test the hypothesis that low-dose prednisone might influence the efficacy of the cytotoxic regimen used, the toxicity profiles of the two treatment regimens and the patterns of treatment failure (relapse, second malignancy, or death) were examined.
  
  
  METHODS
  491 premenopausal and perimenopausal patients with one to three positive axillary lymph nodes included in International (Ludwig) Breast Cancer Study Group (IBCSG) trial I from 1978 to 1981 and randomized to receive CMF or CMFp were analyzed for differences in long-term outcome and toxic events. The 250 patients assigned to CMF and prednisone received on the average 12% more cytotoxic drugs than those who received CMF alone.
  
  
  RESULTS
  The 13-year DFS for the CMFp group was 49% as compared to 52% for CMF alone, and the respective OS percents were 59% and 65%. Several toxic effects such as leukopenia, alopecia, mucositis and induced amenorrhea were reported at a similar incidence in the two treatment groups. Using cumulative incidence methodology for competing risks, we detected a statistically significant increase in first relapse in the skeleton for the CMFp group at 13 years follow-up with a relative risk (RR) of 2.06 [95% confidence interval (CI), 1.23 to 3.46; P = 0.004]. Patients with larger tumors in the CMFp regimen were especially subject to this increase with a RR for failure in the skeleton of 3.32 (95% CI, 1.57 to 7.02; P = 0.0005). CMFp-treated patients also had a larger proportion of second malignancies (not breast cancer), with RR of 3.34 (95% CI, 0.91 to 12.31; P = 0.09).
  
  
  CONCLUSIONS
  Low-dose continuous prednisone added to adjuvant CMF chemotherapy enabled the use of higher doses of cytotoxics. This increased dose had no beneficial effect on treatment outcome, but was associated with an increased risk for bone relapses and a small, not statistically significant increased incidence of second malignancies. The effects of steroids, which are widely used as antiemetics (oral or pulse injection) together with cytotoxics, should be investigated to identify their influence upon treatment outcome.
authors: International Breast Cancer Study Group, Ospedale Civico, Switzerland.
authors: G
authors: G
authors: Marini
authors: S
authors: S
authors: Murray
authors: A
authors: A
authors: Goldhirsch
authors: R D
authors: RD
authors: Gelber
authors: M
authors: M
authors: Castiglione-Gertsch
authors: K N
authors: KN
authors: Price
authors: M H
authors: MH
authors: Tattersall
authors: C M
authors: CM
authors: Rudenstam
authors: J
authors: J
authors: Collins
authors: J
authors: J
authors: Lindtner
authors: F
authors: F
authors: Cavalli
authors: H
authors: H
authors: Cortés-Funes
authors: A
authors: A
authors: Gudgeon
authors: J F
authors: JF
authors: Forbes
authors: E
authors: E
authors: Galligioni
authors: A S
authors: AS
authors: Coates
authors: H J
authors: HJ
authors: Senn
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000453:epidemiology; D011241:Prednisone / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003520:Cyclophosphamide; D005472:Fluorouracil; D011241:Prednisone; D008727:Methotrexate