BACKGROUND: Cyclooxygenase-2 (COX-2) enzyme over expression is reported in many human HCC cell line studies and is linked to tumor cell resistance to chemotherapy-induced apoptosis. We hypothesized that adding a COX-2 inhibitor would improve the therapeutic benefits in patients with HCC. COX-2 is often increased and involved in drug resistance and poor prognosis. METHOD: Between January 2001 and December 2007, 15 patients with MDR-positive-HCC from 34 HCC patients based on tissue and serum liver of glypican-3 and fitting the preset eligibility criteria, were treated with a combination regimen with intravenous infusion of (5-FU) 750 mg once per week, 100mg/day cyclophosphamide (Endoxan) and 400 mg/day celecoxib taken orally in divided doses, while the rest of the patients received only 5-FU and Endoxan. Twenty-one patients (62%) had liver disease associated with hepatitis C virus (HCV) and 5 patients with hepatitis B virus (62%). RESULTS: We found that celecoxib reduced P-glycoprotein with activation of caspase-3 and marked regression of tumor sizes. Sera angiogenic factors (VEGF & bFGF) levels measurement in HCC patients indicated that, the sera levels of both angiogenic factors were reduced significantly (p < 0.05) after treatment. Based on the tumor markers AFP & Glypican-3, 11 of the patients had a PR (11/15), including 3 patients who had normalization of AFP, and four patients had CR (4/15). CONCLUSIONS: These data suggest that the combination of 5-FU, Endoxan and Celecoxib is highly effective palliative regimen for patients with HCC with good performance status (score ≤ 3). The study suggests a framework for Celecoxib-based combination treatment of HCC.
BACKGROUND:Cyclooxygenase-2 (COX-2) enzyme over expression is reported in many human HCC cell line studies and is linked to tumor cell resistance to chemotherapy-induced apoptosis. We hypothesized that adding a COX-2 inhibitor would improve the therapeutic benefits in patients with HCC. COX-2 is often increased and involved in drug resistance and poor prognosis. METHOD: Between January 2001 and December 2007, 15 patients with MDR-positive-HCC from 34 HCC patients based on tissue and serum liver of glypican-3 and fitting the preset eligibility criteria, were treated with a combination regimen with intravenous infusion of (5-FU) 750 mg once per week, 100mg/day cyclophosphamide (Endoxan) and 400 mg/day celecoxib taken orally in divided doses, while the rest of the patients received only 5-FU and Endoxan. Twenty-one patients (62%) had liver disease associated with hepatitis C virus (HCV) and 5 patients with hepatitis B virus (62%). RESULTS: We found that celecoxib reduced P-glycoprotein with activation of caspase-3 and marked regression of tumor sizes. Sera angiogenic factors (VEGF & bFGF) levels measurement in HCC patients indicated that, the sera levels of both angiogenic factors were reduced significantly (p < 0.05) after treatment. Based on the tumor markers AFP & Glypican-3, 11 of the patients had a PR (11/15), including 3 patients who had normalization of AFP, and four patients had CR (4/15). CONCLUSIONS: These data suggest that the combination of 5-FU, Endoxan and Celecoxib is highly effective palliative regimen for patients with HCC with good performance status (score ≤ 3). The study suggests a framework for Celecoxib-based combination treatment of HCC.
Authors: Ahmad R Bassiouny; Amira Z Zaky; Shaymaa A Abdulmalek; Kamal M Kandeel; Alaa Ismail; Marie Moftah Journal: Int J Clin Exp Pathol Date: 2011-10-16
Authors: T F Greten; N P Malek; S Schmidt; J Arends; P Bartenstein; W Bechstein; T Bernatik; M Bitzer; A Chavan; M Dollinger; D Domagk; O Drognitz; M Düx; S Farkas; G Folprecht; P Galle; M Geißler; G Gerken; D Habermehl; T Helmberger; K Herfarth; R T Hoffmann; M Holtmann; P Huppert; T Jakobs; M Keller; J Klempnauer; F Kolligs; J Körber; H Lang; F Lehner; F Lordick; A Lubienski; M P Manns; A Mahnken; M Möhler; C Mönch; P Neuhaus; C Niederau; M Ocker; G Otto; P Pereira; G Pott; J Riemer; K Ringe; U Ritterbusch; E Rummeny; P Schirmacher; H J Schlitt; K Schlottmann; V Schmitz; A Schuler; H Schulze-Bergkamen; D von Schweinitz; D Seehofer; H Sitter; C P Straßburg; C Stroszczynski; D Strobel; A Tannapfel; J Trojan; I van Thiel; A Vogel; F Wacker; H Wedemeyer; H Wege; A Weinmann; C Wittekind; B Wörmann; C J Zech Journal: Z Gastroenterol Date: 2013-11-15 Impact factor: 2.000