Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): A phase 2 multi-institutional trial Journal Article

   

Authors:	Lee, N. Y.; Zhang, Q.; Pfister, D. G.; Kim, J.; Garden, A. S.; Mechalakos, J.; Hu, K.; Le, Q. T.; Colevas, A. D.; Glisson, B. S.; Chan, A. T. C.; Ang, K. K.
Article Title:	Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): A phase 2 multi-institutional trial
Abstract:	Background: We aimed to improve the outcomes for locoregionally advanced nasopharyngeal carcinoma by testing the feasibility and safety of the addition of bevacizumab to chemoradiotherapy. Methods: We enrolled patients older than 18 years with stage IIB-IVB nasopharyngeal carcinoma from 19 centres in North America and Hong Kong. Treatment consisted of three cycles of bevacizumab (15 mg/kg) and cisplatin (100 mg/m 2) both given on days 1, 22, and 43 of radiation (70 Gy) with intensity-modulated radiation therapy delivered over 33 days on a daily basis, Monday through Friday. Patients then received three cycles of bevacizumab (15 mg/kg) and cisplatin (80 mg/m 2), both given on days 64, 85, and 106 after radiation, and three cycles of fluorouracil (1000 mg/m 2 per day), given on days 64-67, 85-88, and 106-109 after radiation. The primary endpoint was the occurrence of treatment-related grade 4 haemorrhage or any grade 5 adverse event in the first year. Analyses were done with all eligible patients who started protocol treatment. The trial is registered at ClinicalTrials.gov, number NCT00408694. Findings: From Dec 13, 2006, to Feb 5, 2009, we enrolled 46 patients, of whom 44 were eligible for analysis. We recorded no grade 3-4 haemorrhages or grade 5 adverse events; nine patients (20%) had a treatment-related grade 1-2 haemorrhage. Nine patients had one or more grade 4 blood or bone marrow-related complication (grade 4 leucopenia was noted in six patients, grade 4 lymphopenia in five, grade 4 neutrophils in five, and grade 4 anaemia in one). One patient had two grade 4 infections with grade 3-4 neutrophils. One patient reported grade 4 tinnitus, one patient reported grade 4 thrombosis, one reported grade 4 radiation mucositis, and two reported grade 4 pharyngolaryngeal pain. With a median follow-up of 2·5 years (IQR 2·1-2·9), the estimated 2 year locoregional progression-free interval was 83·7% (95% CI 72·6-94·9), the 2 year distant metastasis-free interval was 90·8% (82·2-99·5), the 2 year progression-free survival was 74·7% (61·8-87·6), and 2 year overall survival was 90·9% (82·3-99·4). Interpretation: The addition of bevacizumab to standard chemoradiation treatment for patients with nasopharyngeal carcinoma is feasible, and might delay the progression of subclinical distant disease. Funding: National Cancer Institute, USA. © 2012 Elsevier Ltd.
Keywords:	adult; cancer survival; clinical article; treatment response; survival rate; bevacizumab; cisplatin; cancer combination chemotherapy; drug efficacy; drug safety; treatment duration; progression free survival; infection; multiple cycle treatment; phase 2 clinical trial; anemia; allergy; bleeding; lung disease; mucosa inflammation; tinnitus; lymphocytopenia; sexual dysfunction; multicenter study; thrombosis; xerostomia; nasopharynx carcinoma; skin disease; heart arrhythmia; blood clotting disorder; gastrointestinal disease; metabolic disorder; hearing disorder; musculoskeletal disease; endocrine disease; chemoradiotherapy; bone marrow disease; vascular disease; sore throat; lymphatic system disease
Journal Title:	Lancet Oncology
Volume:	13
Issue:	2
ISSN:	1470-2045
Publisher:	Elsevier Science, Inc.
Date Published:	2012-02-01
Start Page:	172
End Page:	180
Language:	English
DOI:	10.1016/s1470-2045(11)70303-5
PROVIDER:	scopus
PUBMED:	22178121
PMCID:	PMC4985181
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84856481199&partnerID=40&md5=09207c4f727a7118d8090f5559dcdcc8
Notes:	--- - "Export Date: 1 March 2012" - "CODEN: LOANB" - "Source: Scopus"

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