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)

Athanassios Argiris, Musie Ghebremichael, Barbara Burtness, Rita S. Axelrod, Ronald C. Deconti, Arlene A. Forastiere

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)3374-3382
Number of pages9
JournalCancer
Volume117
Issue number15
DOIs
StatePublished - Aug 1 2011

Fingerprint

Adenoid Cystic Carcinoma
Doxorubicin
Neck
Head
Bortezomib
Anthracyclines
Anorexia
Neutropenia
Disease-Free Survival
Lung
Survival

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 journalArticle

@article{72dbad11740d4221ad0c7374996b65b8,
title = "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-{\^I}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/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.",
keywords = "adenoid cystic carcinoma, bortezomib, doxorubicin, head and neck cancer",
author = "Athanassios Argiris and Musie Ghebremichael and Barbara Burtness and Axelrod, {Rita S.} and Deconti, {Ronald C.} and Forastiere, {Arlene A.}",
year = "2011",
month = "8",
day = "1",
doi = "10.1002/cncr.25852",
language = "English (US)",
volume = "117",
pages = "3374--3382",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "15",

}

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 -