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.

Details

Serval ID
serval:BIB_E083DCF672DB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
International journal of radiation oncology, biology, physics
Author(s)
Herrera F.G., Chan P., Doll C., Milosevic M., Oza A., Syed A., Pintilie M., Levin W., Manchul L., Fyles A.
ISSN
0360-3016 (Print)
ISSN-L
0360-3016
Publication state
Published
Issued date
01/01/2007
Peer-reviewed
Oui
Volume
67
Number
1
Pages
97-103
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article
Publication Status: ppublish
Abstract
To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer.
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(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).
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(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(5) or IFP and response to treatment (p = 0.2, relative HP(5) change and p = 0.14, relative IFP change).
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.
Keywords
Adult, Aged, Biomarkers, Tumor, Celecoxib, Cell Hypoxia/drug effects, Combined Modality Therapy/methods, Cyclooxygenase 2 Inhibitors/adverse effects, Cyclooxygenase 2 Inhibitors/therapeutic use, Double-Blind Method, Extracellular Fluid/physiology, Female, Follow-Up Studies, Gastrointestinal Diseases/chemically induced, Humans, Leukopenia/chemically induced, Middle Aged, Oxygen Consumption, Prospective Studies, Pyrazoles/adverse effects, Pyrazoles/therapeutic use, Rectovaginal Fistula/chemically induced, Remission Induction, Sulfonamides/adverse effects, Sulfonamides/therapeutic use, Uterine Cervical Neoplasms/drug therapy, Uterine Cervical Neoplasms/metabolism, Uterine Cervical Neoplasms/mortality, Uterine Cervical Neoplasms/radiotherapy
Pubmed
Web of science
Create date
08/04/2020 8:29
Last modification date
09/04/2020 5:26
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