Phase II 2-arm trial of the proteasome inhibitor, PS-341 (bortezomib) in combination with irinotecan or PS-341 alone followed by the addition of irinotecan at time of progression in patients with locally recurrent or metastatic squamous cell carcinoma of the head and neck (E1304): a trial of the Eastern Cooperative Oncology Group.

Abstract

BACKGROUND:

Constitutive activation of nuclear factor κB (NF-κB) is associated with poor prognosis. Irinotecan demonstrates single-agent activity in head and neck cancer but activates NF-κB, promoting cell survival and resistance. Bortezomib is a proteasome inhibitor that inactivates NF-κB.

PATIENTS AND METHODS:

We performed a randomized phase II trial of bortezomib on days 1, 4, 8, and 11 and irinotecan on days 1 and 8 of each 21-day cycle or single-agent bortezomib on days 1, 4, 8, and 11 on a 21-day cycle. The addition of irinotecan to bortezomib was allowed in patients who progressed on bortezomib alone.

RESULTS:

The response rate of bortezomib and irinotecan was 13%. One patient had a partial response to bortezomib alone (response rate 3%). No responses were seen in patients with addition of irinotecan at time of progression on bortezomib.

CONCLUSIONS:

The bortezomib-based regimens evaluated in this study have minimal activity in recurrent or metastatic head and neck cancer.

• Authors: Jill Gilbert, Ju Whei Lee, Athanassios Argiris, Missak Haigentz Jr, Lawrence Eric Feldman, Minyoung Jang, Pattatheyil Arun, Carter Van Waes, Arlene A Forastiere
• Journal: Head & neck (Head Neck) Vol. 35 Issue 7 Pg. 942-8 (Jul 2013) ISSN: 1097-0347 [Electronic] United States
• PMID: 22791234 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published 2012 Wiley Periodicals, Inc.

Chemical References

• Boronic Acids
• Cytokines
• NF-kappa B
• Pyrazines
• Bortezomib
• Irinotecan
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Boronic Acids (administration & dosage)
• Bortezomib
• Camptothecin (administration & dosage, analogs & derivatives)
• Carcinoma, Squamous Cell (diagnosis, drug therapy, secondary)
• Cytokines (blood)
• Disease Progression
• Female
• Head and Neck Neoplasms (diagnosis, drug therapy, secondary)
• Humans
• Irinotecan
• Male
• Middle Aged
• NF-kappa B (genetics, metabolism)
• Pyrazines (administration & dosage)
• Squamous Cell Carcinoma of Head and Neck
• Treatment Outcome