Phase II study of oxaliplatin, capecitabine, and cetuximab in advanced hepatocellular carcinoma.
4604 Background: Hepatocellular carcinomas (HCC) are known to express EGFR, and a ph II study of erlotinib suggested clinical activity of EGFR inhibition. Combinations with EGFR and chemotherapies have been synergistic in a number of settings. We therefore studied the efficacy of capecitabine (cape), oxaliplatin (ox) plus cetuximab (ctx) in patients with advanced HCC. METHODS: Patients had advanced/unresectable HCC by tissue dx or AFP>1,000. Prior chemoembolization was allowed, but no prior systemic therapy. EGFR testing was not required for entry. Patients were treated with cape 850 mg/m(2) bid for 14 days, ox 130 mg/m(2) iv q3wks and ctx 400 mg/m(2) on day one followed by 250 mg/m(2) weekly. A toxicity evaluation was performed after 10 patients were enrolled and doses continued at initial levels throughout the trial. Tumor evaluations were performed q 6 weeks. No particular Childs class was required, but bilirubin had to be < 3, and adequate hematologic and renal parameters were required. RESULTS: 24 of 25 planned pts have completed at least one cycle of therapy. 20 pts are evaluable for response. 2/20 (10%, 95% CI: 1%,-33%) had PR, 13(65%) SD and 5(25%) PD. The most frequent Grade 3 and 4 toxicities have included hyperbilirubinemia (n=8, 35%), fatigue (n = 7, 30%), hypomagnesemia (n = 6, 26%), diarrhea (n = 5, 22%), and hypocalcemia (n = 5, 22%). Three patients died within the first 30 days of treatment, one due to toxicity and 2 due to rapid disease progression. Median TTP is 4.3 mos (95% CI 2.3, 5.0). CONCLUSIONS: The combination of capecitabine, oxaliplating and cetuximab is tolerable for most patients, although diarrhea and electrolyte abnormalities are more pronounced in this population than in other patient populations and led to death in one patient. The combination is associated with a modest rate of radiographic response, but a high rate of stable disease and a promising TTP. Updated TTP and preliminary OS data will be presented at the meeting. [Table: see text].
O'Neil, BH; Bernard, SA; Goldberg, RM; Moore, DT; Garcia, R; Marroquin, C; Morse, MA; Woods, L; Sanoff, HK
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