Abstract
BACKGROUND: Bortezomib, an inhibitor of the 26S proteasome and NF-ÎB, 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/m2 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3374-3382 |
| Number of pages | 9 |
| Journal | Cancer |
| Volume | 117 |
| Issue number | 15 |
| DOIs | |
| State | Published - Aug 1 2011 |
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Keywords
- adenoid cystic carcinoma
- bortezomib
- doxorubicin
- head and neck cancer
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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). / Argiris, Athanassios; Ghebremichael, Musie; Burtness, Barbara; Axelrod, Rita S.; Deconti, Ronald C.; Forastiere, Arlene A.
In: Cancer, Vol. 117, No. 15, 01.08.2011, p. 3374-3382.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
T2 - A trial of the Eastern Cooperative Oncology Group (E1303)
AU - Argiris, Athanassios
AU - Ghebremichael, Musie
AU - Burtness, Barbara
AU - Axelrod, Rita S.
AU - Deconti, Ronald C.
AU - Forastiere, Arlene A.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - BACKGROUND: Bortezomib, an inhibitor of the 26S proteasome and NF-ÎB, 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/m2 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.
AB - BACKGROUND: Bortezomib, an inhibitor of the 26S proteasome and NF-ÎB, 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/m2 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.
KW - adenoid cystic carcinoma
KW - bortezomib
KW - doxorubicin
KW - head and neck cancer
UR - http://www.scopus.com/inward/record.url?scp=79960698423&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960698423&partnerID=8YFLogxK
U2 - 10.1002/cncr.25852
DO - 10.1002/cncr.25852
M3 - Article
C2 - 21246525
AN - SCOPUS:79960698423
VL - 117
SP - 3374
EP - 3382
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 15
ER -