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).

Abstract

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.

• Authors: Athanassios Argiris, Musie Ghebremichael, Barbara Burtness, Rita S Axelrod, Ronald C Deconti, Arlene A Forastiere
• Journal: Cancer (Cancer) Vol. 117 Issue 15 Pg. 3374-82 (Aug 01 2011) ISSN: 1097-0142 [Electronic] United States
• PMID: 21246525 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• Boronic Acids
• Pyrazines
• Bortezomib
• Doxorubicin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Boronic Acids (administration & dosage)
• Bortezomib
• Carcinoma, Adenoid Cystic (drug therapy, pathology)
• Disease Progression
• Doxorubicin (administration & dosage)
• Female
• Head and Neck Neoplasms (drug therapy, pathology)
• Humans
• Liver Neoplasms (drug therapy, pathology, secondary)
• Lung Neoplasms (drug therapy, pathology, secondary)
• Male
• Middle Aged
• Neoplasm Metastasis
• Pyrazines (administration & dosage)
• Recurrence
• Survival Analysis