Abstract
BACKGROUND:
Bortezomib, an inhibitor of the 26S proteasome and NFβΞΊB, 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 0β2, and ejection fraction within normal limits. Patients with stable disease for β₯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:
Twentyβfive 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 singleβagent bortezomib; best response was stable disease in 15 (71%) of 21 evaluable patients. The median progressionβfree 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 3β4 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. Β© 2011 American Cancer Society.