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.
Détails
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Etat: Public
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Etat: Public
Version: de l'auteur⸱e
Licence: Non spécifiée
ID Serval
serval:BIB_E083DCF672DB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
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.
Périodique
International journal of radiation oncology, biology, physics
ISSN
0360-3016 (Print)
ISSN-L
0360-3016
Statut éditorial
Publié
Date de publication
01/01/2007
Peer-reviewed
Oui
Volume
67
Numéro
1
Pages
97-103
Langue
anglais
Notes
Publication types: Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
Mots-clé
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
Open Access
Oui
Création de la notice
08/04/2020 9:29
Dernière modification de la notice
28/03/2023 7:15