Four Versus Six Cycles of Cyclophosphamide/Doxorubicin or Paclitaxel in Adjuvant Breast Cancer

Summary

This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3 positive axillary lymph nodes. Giving additional cancer treatment after surgery may help to lower the risk that the cancer will come back (adjuvant therapy). Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether the standard adjuvant therapy of cyclophosphamide and doxorubicin hydrochloride is more effective than paclitaxel in treating women with breast cancer

Timeline

Start

2002-05

Primary completion

2012-04

Completion

2014-06

Outcome

Missed primary endpoint

paper The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P=.77). PMID 22826271 ↗

paper HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). PMID 24934787 ↗

Publications

• Results Baldwin RM, Owzar K, Zembutsu H, Chhibber A, Kubo M, Jiang C, Watson D, Eclov RJ, Mefford J, McLeod HL, Friedman PN, Hudis CA, Winer EP, Jorgenson EM, Witte JS, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL. A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. Clin Cancer Res. 2012 Sep 15;18(18):5099-109. doi: 10.1158/1078-0432.CCR-12-1590. Epub 2012 Jul 27.
• Results Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. 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. J Clin Oncol. 2012 Nov 20;30(33):4071-6. doi: 10.1200/JCO.2011.40.6405. Epub 2012 Jul 23.
• Barginear M, Dueck AC, Allred JB, Bunnell C, Cohen HJ, Freedman RA, Hurria A, Kimmick G, Le-Rademacher JG, Lichtman S, Muss HB, Shulman LN, Copur MS, Biggs D, Ramaswamy B, Lafky JM, Jatoi A. Age and the Risk of Paclitaxel-Induced Neuropathy in Women with Early-Stage Breast Cancer (Alliance A151411): Results from 1,881 Patients from Cancer and Leukemia Group B (CALGB) 40101. Oncologist. 2019 May;24(5):617-623. doi: 10.1634/theoncologist.2018-0298. Epub 2018 Nov 8.
• Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. doi: 10.1200/JCO.2013.53.7142. Epub 2014 Jun 16.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cyclophosphamide	Other / unclassified	—	Intravenous
Subject	Doxorubicin	Other / unclassified	—	Intravenous
Subject	Paclitaxel	Small molecule	80 mg/m2	Intravenous
Subject	Paclitaxel	Small molecule	175 mg/m2	Intravenous

Indications