Phase I trial using the proteasome inhibitor bortezomib and concurrent chemoradiotherapy for head-and-neck malignancies

Gregory J. Kubicek, Rita S. Axelrod, Mitchell MacHtay, Peter H. Ahn, Pramila R. Anne, Shannon Fogh, David Cognetti, Thomas J. Myers, Walter J. Curran, Adam P. Dicker

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27 Scopus citations


Purpose: Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. Methods and Materials: Eligible patients received cisplatin once weekly at 30 mg/m 2 per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m 2 and escalation levels of 1.0 and 1.3 mg/m 2. Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. Results: We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m 2 (7 patients), 1.0 mg/m 2 (10 patients), and 1.3 mg/m 2 (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). Conclusion: Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m 2 in patients previously treated for HNC and 1.3 mg/m 2 in radiation-naive patients.

Original languageEnglish (US)
Pages (from-to)1192-1197
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
StatePublished - Jul 15 2012

All Science Journal Classification (ASJC) codes

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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