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Title: A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment

Abstract

Purpose: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. Methods and Materials: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP{sub 5}) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). Results: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP{sub 5} did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP{sub 5}more » or IFP and response to treatment (p = 0.2, relative HP{sub 5} change and p = 0.14, relative IFP change). Conclusions: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [1];  [3];  [1];  [1];  [4]
  1. Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)
  2. Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)
  3. Department of Clinical Study Coordination and Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)
  4. Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada). E-mail: Anthony.Fyles@rmp.uhn.on.ca
Publication Date:
OSTI Identifier:
20850300
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.08.024; PII: S0360-3016(06)02782-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOLOGICAL MARKERS; CARCINOMAS; CHEMOTHERAPY; COMBINED THERAPY; HEALTH HAZARDS; ORAL CAVITY; PATIENTS; TOXICITY; WOMEN

Citation Formats

Herrera, Fernanda G., Chan, Philip, Doll, Corinne, Milosevic, Michael, Oza, Amit, Syed, Amy, Pintilie, Melania, Levin, Wilfred, Manchul, Lee, and Fyles, Anthony. A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.08.024.
Herrera, Fernanda G., Chan, Philip, Doll, Corinne, Milosevic, Michael, Oza, Amit, Syed, Amy, Pintilie, Melania, Levin, Wilfred, Manchul, Lee, & Fyles, Anthony. A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment. United States. doi:10.1016/j.ijrobp.2006.08.024.
Herrera, Fernanda G., Chan, Philip, Doll, Corinne, Milosevic, Michael, Oza, Amit, Syed, Amy, Pintilie, Melania, Levin, Wilfred, Manchul, Lee, and Fyles, Anthony. Mon . "A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment". United States. doi:10.1016/j.ijrobp.2006.08.024.
@article{osti_20850300,
title = {A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment},
author = {Herrera, Fernanda G. and Chan, Philip and Doll, Corinne and Milosevic, Michael and Oza, Amit and Syed, Amy and Pintilie, Melania and Levin, Wilfred and Manchul, Lee and Fyles, Anthony},
abstractNote = {Purpose: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. Methods and Materials: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP{sub 5}) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). Results: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP{sub 5} did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP{sub 5} or IFP and response to treatment (p = 0.2, relative HP{sub 5} change and p = 0.14, relative IFP change). Conclusions: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response.},
doi = {10.1016/j.ijrobp.2006.08.024},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 67,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}