Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: Final results of Cancer and Leukemia Group B protocol 9840 Journal Article

  

Authors:	Seidman, A. D.; Berry, D.; Cirrincione, C.; Harris, L.; Muss, H.; Marcom, P. K.; Gipson, G.; Burstein, H.; Lake, D.; Shapiro, C. L.; Ungaro, P.; Norton, L.; Winer, E.; Hudis, C.
Article Title:	Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: Final results of Cancer and Leukemia Group B protocol 9840
Abstract:	Purpose: Phase II trials suggested that weekly paclitaxel might be more effective and less toxic than every-3-weeks administration for metastatic breast cancer (MBC). Cancer and Leukemia Group B (CALGB) protocol 9840 was initiated to address this question. Subsequently trastuzumab was demonstrated to improve outcomes of paclitaxel therapy for human epidermal growth factor receptor-2 (HER-2)-positive patients, and was therefore incorporated. Because inhibition of HER-family signaling had potential efficacy even without HER-2 overexpression, we randomly assigned for trastuzumab in this population. Patients and Methods: Patients were randomly assigned to paclitaxel 175 mg/m2 every 3 weeks or 80 mg/m2 weekly. After the first 171 patients, all HER-2-positive patients received trastuzumab; HER-2 nonoverexpressors were randomly assigned for trastuzumab, in addition to paclitaxel schedule. A total of 577 patients were treated on 9840. An additional 158 patients were included in analyses, for combined sample of 735. The primary end point was response rate (RR); secondary end points were time to progression (TTP), overall survival, and toxicity. Primary comparisons were between weekly versus every-3-weeks paclitaxel, and trastuzumab versus no trastuzumab in HER-2 nonoverexpressors. Results: In the combined sample, weekly paclitaxel was superior to every-3-weeks administration: RR (42% v 29%, unadjusted odds ratio [OR] = 1.75; P = .0004), TTP (median, 9 v 5 months; adjusted HR = 1.43; P < .0001), and survival (median, 24 v 12 months; adjusted HR = 1.28; P = .0092). For HER-2 nonoverexpressors, trastuzumab did not improve efficacy. Grade 3 neuropathy was more common with weekly dosing (24% v 12%; P = .0003). Conclusion: Weekly paclitaxel is more effective than every-3-weeks administration for MBC. Trastuzumab did not improve efficacy for HER-2 nonoverexpressors. Neurotoxicity is a treatment-limiting toxicity for weekly paclitaxel. © 2008 by American Society of Clinical Oncology.
Keywords:	cancer survival; controlled study; treatment outcome; treatment response; middle aged; leukemia; major clinical study; clinical trial; mortality; cancer growth; drug efficacy; paclitaxel; antineoplastic agent; metabolism; gene overexpression; metastasis; controlled clinical trial; breast cancer; blood toxicity; neuropathy; randomized controlled trial; antineoplastic combined chemotherapy protocols; myalgia; epidermal growth factor receptor 2; breast neoplasms; monoclonal antibody; arthralgia; dyspnea; febrile neutropenia; loading drug dose; kaplan-meiers estimate; biosynthesis; antibodies, monoclonal; dosage schedule comparison; multicenter study; breast tumor; receptor, erbb-2; phase 3 clinical trial; kaplan meier method; trastuzumab; granulocytopenia; oncogene neu
Journal Title:	Journal of Clinical Oncology
Volume:	26
Issue:	10
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2008-04-01
Start Page:	1642
End Page:	1649
Language:	English
DOI:	10.1200/jco.2007.11.6699
PUBMED:	18375893
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-43249115659&partnerID=40&md5=102bc07b74835273db91d268a8f7d5fc
Notes:	--- - Article; Proceedings Paper - 40th Annual Meeting of the American-Society-of-Clinical-Oncology - JUN 05-08, 2004 - New Orleans, LA - "Cited By (since 1996): 139" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"

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