Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients. German Breast Cancer Study Group.
OBJECTIVE
In 1984, the German Breast Cancer Study Group (GBSG) started a multicenter randomized clinical trial to compare the effectiveness of three versus six cycles of 500 mg/m2 cyclophosphamide, 40 mg/m2 methotrexate, and 600 mg/m2 fluorouracil (CMF) on day 1 and 8 starting perioperatively with or without tamoxifen (TAM) (3 x 10 mg/d for 2 years). The aim of the trial was to compare recurrence-free and overall survival between the different treatment modalities.


METHODS
During 5 years, 41 institutions randomized 473 patients (3 x CMF: 145; 3 x CMF + TAM: 93; 6 x CMF 144; 6 x CMF + TAM: 91). Until March 31, 1992, median follow-up time was 56 months with 197 events for disease-free survival and 116 deaths observed. This provides a power of approximately 80% to detect a potential treatment difference corresponding to a relative risk (RR) of 0.67 for recurrence-free survival. Treatment modalities and various patient characteristics were evaluated by means of a multivariate Cox regression analysis.


RESULTS
No significant difference in recurrence-free survival was observed with respect to hormonal therapy (RR = 0.75 TAM v no TAM; 95% confidence interval [CI], 0.54 to 1.04; P = .08) as well as duration of chemotherapy (RR = 0.90 of 6 x CMF v 3 x CMF; 95% CI, 0.67 to 1.19; P = .45). Similar results were obtained for overall survival. The multivariate analysis revealed a significant prognostic impact of the number of positive lymph nodes and the progesterone receptor level on recurrence-free survival. Compliance with chemotherapy within the range of 85% to 115% of the target dose was achieved in 94% and 78% of the patients randomized to 3 x CMF and 6 x CMF, respectively. Sufficient compliance with TAM was reported for 141 patients (93%).


CONCLUSIONS
At this stage of follow-up, six courses of CMF are not superior to three courses with respect to recurrence-free survival.
Schumacher
M
M
Institut für Medizinische Biometrie und Informatik, Universität Freiburg, Germany.
Bastert
G
G
Bojar
H
H
Hübner
K
K
Olschewski
M
M
Sauerbrei
W
W
Schmoor
C
C
Beyerle
C
C
Neumann
R L
RL
Rauschecker
H F
HF
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D015999:Multivariate Analysis; D010349:Patient Compliance; D012044:Regression Analysis; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage
D013629:Tamoxifen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate