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Argiris A , Ghebremichael M , Burtness B , Axelrod RS , Deconti RC , Forastiere AA
A Phase 2 Trial of Bortezomib Followed by the Addition of Doxorubicin at Progression in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck A Trial of the Eastern Cooperative Oncology Group (E1303)
Cancer. 2011 Aug;117(15) :3374-3382
PMCID: PMC3135694   
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BACKGROUND: Bortezomib, an inhibitor of the 26S proteasome and NF-kappa B, may have antitumor activity in adenoid cystic carcinoma (ACC). Preclinical studies have shown synergy between bortezomib and doxorubicin. METHODS: Eligibility criteria included incurable ACC, any number of prior therapies but without an anthracycline, unidimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and ejection fraction within normal limits. Patients with stable disease for >= 9 months were excluded. Patients received bortezomib 1.3 mg/m(2) by intravenous (IV) push on Days 1, 4, 8, and 11, every 21 days until progression. Doxorubicin 20 mg/m(2) IV on Days 1 and 8 was added at the time of progression. RESULTS: Twenty-five patients were enrolled, of whom 24 were eligible; the most common distant metastatic sites were the lung (n = 22) and the liver (n = 7). There was no objective response with single-agent bortezomib; best response was stable disease in 15 (71%) of 21 evaluable patients. The median progression-free survival and overall survival were 6.4 months and 21 months, respectively. Of 10 evaluable patients who received bortezomib plus doxorubicin, 1 had a partial response, and 6 had stable disease. The most frequent toxicity with bortezomib was grade 3 sensory neuropathy (16%). With bortezomib plus doxorubicin, serious toxicities seen more than once were grade 3-4 neutropenia (n = 3) and grade 3 anorexia (n = 2). CONCLUSIONS: Bortezomib was well tolerated and resulted in disease stabilization in a high percentage of patients but no objective responses. The combination of bortezomib and doxorubicin was also well tolerated and may warrant further investigation in ACC. Cancer 2011;117:3374-82. (C) 2011 American Cancer Society
Argiris, Athanassios Ghebremichael, Musie Burtness, Barbara Axelrod, Rita S. Deconti, Ronald C. Forastiere, Arlene A. National Cancer Institute, National Institutes of Health; Department of Health and Human Services; Millennium Pharmaceuticals, Inc.; [CA23318]; [CA66636]; [CA21115]; [CA39229]; [CA17145]; [CA27525]; [CA13650]; [CA16116] This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA39229, CA17145, CA27525, CA13650, and CA16116 and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Dr. Argiris has received research support from Millennium Pharmaceuticals, Inc. 29 Wiley-blackwell Malden 797dd