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.
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.


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.
Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. jill.gilbert@vanderbilt.edu
Jill
J
Gilbert
Ju Whei
JW
Lee
Athanassios
A
Argiris
Missak
M
Haigentz
Lawrence Eric
LE
Feldman
Minyoung
M
Jang
Pattatheyil
P
Arun
Carter
C
Van Waes
Arlene A
AA
Forastiere
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
D001897:Boronic Acids; D016207:Cytokines; D016328:NF-kappa B; D011719:Pyrazines; D000069286:Bortezomib; D000077146:Irinotecan; D002166:Camptothecin