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

Head Neck. 2013 Jul;35(7):942-8. doi: 10.1002/hed.23046. Epub 2012 Jul 13.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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