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Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies

Abstract

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{sup 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{sup 2} and escalation levels of 1.0 and 1.3 mg/m{sup 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{sup 2} (7 patients), 1.0 mg/m{sup 2} (10 patients), and 1.3 mg/m{sup 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  More>>
Authors:
Kubicek, Gregory J; [1]  Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)]; Axelrod, Rita S; [2]  Machtay, Mitchell; [1]  Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States)]; Ahn, Peter H; Anne, Pramila R; [1]  Fogh, Shannon; [1]  Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States)]; Cognetti, David; [3]  Myers, Thomas J; [4]  Curran, Walter J; [1]  Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org [1] 
  1. Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States)
  2. Department of Medical Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States)
  3. Department of Otolaryngology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States)
  4. EMD Serono, Rockland, MA (United States)
Publication Date:
Jul 15, 2012
Product Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 83; Journal Issue: 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; COMBINED THERAPY; HEAD; IRRADIATION; NECK; NEOPLASMS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; TOXICITY
OSTI ID:
22058962
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0360-3016; CODEN: IOBPD3; Other: PII: S0360-3016(11)03221-4; TRN: US12R2846019444
Availability:
Available from http://dx.doi.org/10.1016/j.ijrobp.2011.09.023
Submitting Site:
USN
Size:
page(s) 1192-1197
Announcement Date:
Feb 21, 2013

Citation Formats

Kubicek, Gregory J, Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)], Axelrod, Rita S, Machtay, Mitchell, Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States)], Ahn, Peter H, Anne, Pramila R, Fogh, Shannon, Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States)], Cognetti, David, Myers, Thomas J, Curran, Walter J, and Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org. Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2011.09.023.
Kubicek, Gregory J, Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)], Axelrod, Rita S, Machtay, Mitchell, Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States)], Ahn, Peter H, Anne, Pramila R, Fogh, Shannon, Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States)], Cognetti, David, Myers, Thomas J, Curran, Walter J, & Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org. Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies. United States. https://doi.org/10.1016/J.IJROBP.2011.09.023
Kubicek, Gregory J, Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)], Axelrod, Rita S, Machtay, Mitchell, Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States)], Ahn, Peter H, Anne, Pramila R, Fogh, Shannon, Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States)], Cognetti, David, Myers, Thomas J, Curran, Walter J, and Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org. 2012. "Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies." United States. https://doi.org/10.1016/J.IJROBP.2011.09.023.
@misc{etde_22058962,
title = {Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies}
author = {Kubicek, Gregory J, Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)], Axelrod, Rita S, Machtay, Mitchell, Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States)], Ahn, Peter H, Anne, Pramila R, Fogh, Shannon, Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States)], Cognetti, David, Myers, Thomas J, Curran, Walter J, and Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org}
abstractNote = {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{sup 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{sup 2} and escalation levels of 1.0 and 1.3 mg/m{sup 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{sup 2} (7 patients), 1.0 mg/m{sup 2} (10 patients), and 1.3 mg/m{sup 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{sup 2} in patients previously treated for HNC and 1.3 mg/m{sup 2} in radiation-naive patients.}
doi = {10.1016/J.IJROBP.2011.09.023}
journal = []
issue = {4}
volume = {83}
journal type = {AC}
place = {United States}
year = {2012}
month = {Jul}
}