Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95.
OBJECTIVE
To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor-negative or stage III tumor with five or more positive axillary nodes.


METHODS
Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2 plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS).


RESULTS
After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor-positive tumors benefited significantly from DI-EC.


CONCLUSIONS
There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.
CSL Ltd, 45 Poplar Rd,Parkville, Vic 3052, Australia. russell.basser@csl.com.au
Basser
Russell L
RL
O'Neill
Anne
A
Martinelli
Giovanni
G
Green
Michael D
MD
Peccatori
Fedro
F
Cinieri
Saverio
S
Coates
Alan S
AS
Gelber
Richard D
RD
Aebi
Stefan
S
Castiglione-Gertsch
Monica
M
Viale
Guiseppe
G
Price
Karen N
KN
Goldhirsch
Aron
A
D000328:Adult; D000368:Aged; D000568:Amenorrhea / Q000139:chemically induced; D018943:Anthracyclines / Q000008:administration & dosage; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011994:Recombinant Proteins; D018570:Risk Assessment; D012307:Risk Factors; D013234:Stem Cells; D016019:Survival Analysis; D016896:Treatment Outcome
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim