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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
Author(s) -
Argiris Athanassios,
Ghebremichael Musie,
Burtness Barbara,
Axelrod Rita S.,
Deconti Ronald C.,
Forastiere Arlene A.
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25852
Subject(s) - bortezomib , medicine , neutropenia , adenoid cystic carcinoma , proteasome inhibitor , oncology , progressive disease , doxorubicin , multiple myeloma , gastroenterology , surgery , chemotherapy , carcinoma
BACKGROUND: Bortezomib, an inhibitor of the 26S proteasome and NF‐κB, 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. © 2011 American Cancer Society.