A randomized single-institution study of high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC) in apical node-positive breast cancer

PURPOSE: To determine the influence of the epirubicin dose in operable node-positive breast cancer patients with factors of poor prognosis. PATIENTS AND METHODS: Between April 1990 and July 1993, 565 operable breast cancer patients with either more than three positive nodes or between one and three positive nodes with Scarff Bloom Richardson grade ≥ 2 and hormone receptor negativity were randomized after surgery to receive either fluorouracil 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 every 21 days for six cycles (FEC 50) or the same regimen except with epirubicin dose of 100 mg/m2 (FEC 100). Postmenopausal patients received tamoxifen 30 mg/d for 3 years at the beginning of chemotherapy. Radiotherapy was delivered at the end of chemotherapy in both groups. RESULTS: The median follow-up was 67 months. The 5-year disease-free survival (DFS) was 54.8% with FEC 50 and 66.3% with FEC 100 (P = .03). The 5-year overall survival (OS) was 65.3% and 77.4%, respectively (P = .007). The mean relative dose-intensity was similar in the two groups (90.3% and 86.1%, respectively). Neutropenia and anemia were significantly more frequent in FEC 100 (P < 10−3), as were nausea-vomiting (P = .008) and stomatitis and alopecia (P < 10−3). Nine cases of grade 3 infection occurred only with FEC 100, and no toxic deaths occurred. Three cases of acute cardiac toxicity were observed (FEC50 = 1, FEC100 = 2) and 10 patients (FEC50 = 6, FEC100 = 4) presented delayed cardiac dysfunctions. Two cases of secondary leukemia were observed (acute lymphatic leukemia with FEC 50 and acute myelogenous leukemia with FEC 100). CONCLUSION: After 5 years of follow-up, the increased epirubicin dose led to a significant benefit in terms of DFS and OS, with a high survival rate among patients with poor-prognosis breast cancer.

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Long-Term Benefit of High-Dose Epirubicin in Adjuvant Chemotherapy for Node-Positive Breast Cancer: 15-Year Efficacy Results of the Belgian Multicentre Study

Journal of Clinical Oncology ◽

10.1200/jco.2008.17.2155 ◽

2009 ◽

Vol 27 (5) ◽

pp. 720-725 ◽

Cited By ~ 15

Author(s):

Evandro de Azambuja ◽

Marianne Paesmans ◽

Marc Beauduin ◽

Anita Vindevoghel ◽

Nathalie Cornez ◽

...

Keyword(s):

Breast Cancer ◽

Multicenter Trial ◽

High Dose ◽

Event Free Survival ◽

Free Survival ◽

Node Positive ◽

Hazard Ratios ◽

Term Benefit ◽

Positive Breast Cancer

Purpose The 4-year results of this trial demonstrated that a higher dose of epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin, 60 mg/m2 (EC), for event-free survival (EFS; 27% reduction), but is not superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF) in the adjuvant treatment of node-positive breast cancer. Herein we report the 15-year data on efficacy and long-term toxicity of this three-arm Belgian multicenter trial. Patients and Methods Between March 1988 and December 1996, 777 eligible patients were randomly assigned to six cycles of CMF, eight cycles of EC, or eight cycles HEC. Results The 15-year EFS was 45% for patients who received CMF, 39% for patients who received EC, and 50% for patients who received HEC. The hazard ratios (HR) were 0.77 for HEC versus EC (95% CI, 0.60 to 0.98; P = .03), 0.90 for HEC versus CMF (P = .39), and 0.86 for EC versus CMF (P = .21). No difference in overall survival (OS) was seen. Cardiac toxicity was more frequent with HEC than with CMF (11 patients v 1 patient; P = .006), but no more than with EC (P = .21). Conclusion Treatment with HEC demonstrated superior EFS when compared with lower-dose epirubicin. However, we do not recommend the use of HEC regimen in daily clinical practice, mainly because of the higher risk of cardiotoxicity related to the cumulative doses of epirubicin and the lack of superiority of anthracyclines over CMF in our study.

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Abstract P1-01-02: Sentinel Node Biopsy Alone for Node Positive Breast Cancer, a Twelve Year Experience at a Single Institution

10.1158/0008-5472.sabcs10-p1-01-02 ◽

2010 ◽

Author(s):

L Spiguel ◽

K Yao ◽

A Gorchow ◽

H Du ◽

DJ Winchester ◽

...

Keyword(s):

Breast Cancer ◽

Sentinel Node ◽

Sentinel Node Biopsy ◽

Single Institution ◽

Node Positive ◽

Node Biopsy ◽

Positive Breast Cancer

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Adjuvant treatment of high-risk stage II breast cancer with doxorubicin followed by high-dose chemotherapy and autologous stem-cell transplantation: a single-institution experience with 132 consecutive patients

Bone Marrow Transplantation ◽

10.1038/sj.bmt.1703856 ◽

2003 ◽

Vol 31 (8) ◽

pp. 655-661 ◽

Cited By ~ 3

Author(s):

S M Stemmer ◽

I Hardan ◽

H Raz ◽

A K Adamou ◽

M Inbar ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Adjuvant Treatment ◽

High Dose Chemotherapy ◽

High Dose ◽

Single Institution

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Drug-Metabolizing Enzyme Polymorphisms Predict Clinical Outcome in a Node-Positive Breast Cancer Cohort

Journal of Clinical Oncology ◽

10.1200/jco.2005.06.208 ◽

2005 ◽

Vol 23 (24) ◽

pp. 5552-5559 ◽

Cited By ~ 35

Author(s):

Angela DeMichele ◽

Richard Aplenc ◽

Jeffrey Botbyl ◽

Theresa Colligan ◽

Lisa Wray ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Clinical Outcome ◽

High Dose ◽

Group Status ◽

Genotype Group ◽

Functional Polymorphisms ◽

Node Positive ◽

Positive Breast Cancer

Purpose Adjuvant chemotherapy cures only a subset of women with nonmetastatic breast cancer. Genotypes in drug-metabolizing enzymes, including functional polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST), may predict treatment-related outcomes. Patients and Methods We examined CYP3A4*1B, CYP3A5*3, and deletions in GST μ (GSTM1) and θ (GSTT1), as well as a priori–defined combinations of polymorphisms in these genes. Using a cohort of 90 node-positive breast cancer patients who received anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem-cell rescue, we estimated the effect of genotype and other known prognostic factors on disease-free survival (DFS) and overall survival (OS). Results Patients who carried homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer DFS (P = .021) and a four-fold poorer OS (P = .031) compared with individuals who did not carry any CYP3A4*1B or CYP3A5*3 variants but had deletions in both GSTT1 and GSTM1 (denoted high-drug genotype group). After adjustment for other significant prognostic factors, the low-drug genotype group retained a significantly poorer DFS (hazard ratio [HR] = 4.9; 95% CI, 1.7 to 14.6; P = .004) and OS (HR = 4.8; 95% CI, 1.8 to 12.9; P = .002) compared with the high- and intermediate-drug combined genotype group. In the multivariate model, having low-drug genotype group status had a greater impact on clinical outcome than estrogen receptor status. Conclusion Combined genotypes at CYP3A4, CYP3A5, GSTM1, and GSTT1 influence the probability of treatment failure after high-dose adjuvant chemotherapy for node-positive breast cancer.

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