BACKGROUND: Hepatocellular carcinoma (HCC) is frequently resistant to chemotherapy. However, epidermal growth factor receptor (EGFR) inhibition has demonstrated activity in HCC and overcomes chemotherapy resistance in other settings. We studied the efficacy of combining the anti-EGFR antibody cetuximab with capecitabine and oxaliplatin in advanced HCC. METHODS: Patients who had chemotherapy-naive advanced/unresectable HCC and any Childs-Pugh-class chronic liver disease (provided bilirubin was <3 mg/dl) received capecitabine 850 mg/m(2) bid days 1-14, oxaliplatin 130 mg/m(2) day 1, and cetuximab 400 mg/m(2) day 1 then 250 mg/m(2) weekly for each 21 day cycle. RESULTS: Twenty-nine patients received any protocol therapy, but 24 completed at least one cycle. Of the 24 patients evaluable for response, 3 had a partial response (12.5%, 95% confidence interval [CI], 3-32%) and 17 had stable disease (71%), for a disease control rate of 83%. Of patients with an elevated AFP, 57% had a >50% reduction in AFP. Median time to progression was 4.5 months (95% CI, 3.2-6.4), and overall survival was 4.4 months (95% CI, 2.4-7.3). Most common toxicities included diarrhea (13 patients, 45%), fatigue (12 patients, 41%), and hypomagnesemia (12 patients, 41%). Fatigue (6 patients) and diarrhea (5 patients) were the most common grade 3-4 toxicities. Three patients died within the first 30 days of treatment (one of toxicity, two of liver failure presumed to be related to disease progression). CONCLUSIONS: The capecitabine/oxaliplatin/cetuximab combination was tolerable, though diarrhea was pronounced, in this population. The combination was associated with a modest response rate, but a high rate of AFP response and radiographic stable disease. Time to progression and overall survival were shorter than would be expected for treatment with sorafenib.
BACKGROUND:Hepatocellular carcinoma (HCC) is frequently resistant to chemotherapy. However, epidermal growth factor receptor (EGFR) inhibition has demonstrated activity in HCC and overcomes chemotherapy resistance in other settings. We studied the efficacy of combining the anti-EGFR antibody cetuximab with capecitabine and oxaliplatin in advanced HCC. METHODS:Patients who had chemotherapy-naive advanced/unresectable HCC and any Childs-Pugh-class chronic liver disease (provided bilirubin was <3 mg/dl) received capecitabine 850 mg/m(2) bid days 1-14, oxaliplatin 130 mg/m(2) day 1, and cetuximab 400 mg/m(2) day 1 then 250 mg/m(2) weekly for each 21 day cycle. RESULTS: Twenty-nine patients received any protocol therapy, but 24 completed at least one cycle. Of the 24 patients evaluable for response, 3 had a partial response (12.5%, 95% confidence interval [CI], 3-32%) and 17 had stable disease (71%), for a disease control rate of 83%. Of patients with an elevated AFP, 57% had a >50% reduction in AFP. Median time to progression was 4.5 months (95% CI, 3.2-6.4), and overall survival was 4.4 months (95% CI, 2.4-7.3). Most common toxicities included diarrhea (13 patients, 45%), fatigue (12 patients, 41%), and hypomagnesemia (12 patients, 41%). Fatigue (6 patients) and diarrhea (5 patients) were the most common grade 3-4 toxicities. Three patients died within the first 30 days of treatment (one of toxicity, two of liver failure presumed to be related to disease progression). CONCLUSIONS: The capecitabine/oxaliplatin/cetuximab combination was tolerable, though diarrhea was pronounced, in this population. The combination was associated with a modest response rate, but a high rate of AFP response and radiographic stable disease. Time to progression and overall survival were shorter than would be expected for treatment with sorafenib.
Authors: Winnie Yeo; Tony S Mok; Benny Zee; Thomas W T Leung; Paul B S Lai; Wan Y Lau; Jane Koh; Frankie K F Mo; Simon C H Yu; Anthony T Chan; Pun Hui; Brigette Ma; Kwok C Lam; Wing M Ho; Herman T Wong; Amanda Tang; Philip J Johnson Journal: J Natl Cancer Inst Date: 2005-10-19 Impact factor: 13.506
Authors: Timothy W Synold; Chris H Takimoto; James H Doroshow; David Gandara; Sridhar Mani; Scot C Remick; Daniel L Mulkerin; Anne Hamilton; Sunil Sharma; Ramesh K Ramanathan; Heinz Josef Lenz; Martin Graham; Jeffrey Longmate; Bennett M Kaufman; Percy Ivy Journal: Clin Cancer Res Date: 2007-06-15 Impact factor: 12.531
Authors: Shirin Khambata-Ford; Christopher R Garrett; Neal J Meropol; Mark Basik; Christopher T Harbison; Shujian Wu; Tai W Wong; Xin Huang; Chris H Takimoto; Andrew K Godwin; Benjamin R Tan; Smitha S Krishnamurthi; Howard A Burris; Elizabeth A Poplin; Manuel Hidalgo; Jose Baselga; Edwin A Clark; David J Mauro Journal: J Clin Oncol Date: 2007-08-01 Impact factor: 44.544
Authors: Bert H O'Neil; Robert Allen; David R Spigel; Thomas E Stinchcombe; Dominic T Moore; Jordan D Berlin; Richard M Goldberg Journal: J Clin Oncol Date: 2007-08-20 Impact factor: 44.544
Authors: Andrew X Zhu; Keith Stuart; Lawrence S Blaszkowsky; Alona Muzikansky; Donald P Reitberg; Jeffrey W Clark; Peter C Enzinger; Pankaj Bhargava; Jeffrey A Meyerhardt; Kerry Horgan; Charles S Fuchs; David P Ryan Journal: Cancer Date: 2007-08-01 Impact factor: 6.860
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: Y Ito; T Takeda; M Sakon; M Tsujimoto; S Higashiyama; K Noda; E Miyoshi; M Monden; N Matsuura Journal: Br J Cancer Date: 2001-05-18 Impact factor: 7.640
Authors: V Boige; J-L Raoul; J-P Pignon; O Bouché; J-F Blanc; L Dahan; J-L Jouve; N Dupouy; M Ducreux Journal: Br J Cancer Date: 2007-09-18 Impact factor: 7.640
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