Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101 Journal Article
| Authors: | Shulman, L. N.; Cirrincione, C. T.; Berry, D. A.; Becker, H. P.; Perez, E. A.; O'Regan, R.; Martino, S.; Atkins, J. N.; Mayer, E.; Schneider, C. J.; Kimmick, G.; Norton, L.; Muss, H.; Winer, E. P.; Hudis, C. |
| Article Title: | Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101 |
| Abstract: | Purpose: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/ cyclophosphamide (AC), but with reduced toxicity. Patients and Methods: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). Results: A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P = .77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P = .44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. Conclusion: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome. © 2012 by American Society of Clinical Oncology. |
| Keywords: | adult; cancer survival; aged; aged, 80 and over; disease-free survival; middle aged; major clinical study; overall survival; neutropenia; doxorubicin; treatment duration; paclitaxel; adjuvant therapy; cancer adjuvant therapy; comparative study; chemotherapy, adjuvant; follow up; lymphatic metastasis; multiple cycle treatment; breast cancer; neuropathy; antineoplastic combined chemotherapy protocols; drug administration schedule; epidermal growth factor receptor 2; risk factors; cyclophosphamide; breast neoplasms; fever; myelodysplastic syndrome; cardiotoxicity; therapy effect; phase 3 clinical trial; restrictive cardiomyopathy; recurrence free survival; factorial design; left ventricular systolic dysfunction |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 30 |
| Issue: | 33 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2012-11-01 |
| Start Page: | 4071 |
| End Page: | 4076 |
| Language: | English |
| DOI: | 10.1200/jco.2011.40.6405 |
| PROVIDER: | scopus |
| PMCID: | PMC3494835 |
| PUBMED: | 22826271 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 December 2012" - "CODEN: JCOND" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work