For patients with advanced hepatocellular carcinoma who are not candidates for surgical resection, liver transplantation, or localized tumor ablation, systemic chemotherapy remains an option. Unfortunately, hepatocellular carcinoma is a relatively chemotherapy-resistant tumor; therefore, outcomes using this mode of treatment are less than satisfactory. The only FDA approved drug for this cancer is Nexavar (sorafenib). Sorafenib, a multitargeted oral kinase inhibitor, has recently been shown in a phase III trial to prolong survival in patients with hepatocellular carcinoma. The National Comprehensive Cancer Network (NCCN) guidelines(2011, HCC-7) for hepatocellular carcinoma recommend sorafenib as a treatment option .
The most active single agent drugs tested have been doxorubicin, cisplatin, and fluorouracil. More recently, gemcitabine and capecitabine have been evaluated in clinical trials; response rates have been low and less than satisfactory; cisplatin-based combination regimens, such as gemcitabine and cisplatin (or oxaliplatin), have shown improved response rates around 20%, but to date, no survival advantage as compared to supportive care alone has been shown. No difference seems to exist in response rates between 2- or 3-drug regimens. Moreover, some of these combination regimens cause considerable toxicity. The combination of bevacizumab with gemcitabine and oxaliplatin, produced a 20% response rate with an additional 27% of patients who had stable disease.
More recently Foflox was shown to be effective. Nexavar and Adriamycin were reported in 2010 to be better than Adriamycin. Mdian time to progression was 6.4 months in the sorafenib-doxorubicin group (95% confidence interval [CI], 4.8-9.2), and 2.8 months (95% CI, 1.6-5) in the doxorubicin-placebo monotherapy group (P = .02). Median overall survival was 13.7 months (95% CI, 8.9–not reached) and 6.5 months (95% CI, 4.5-9.9; P = .006), and progression-free survival was 6.0 months (95% CI, 4.6-8.6) and 2.7 months (95% CI, 1.4-2.8) in these groups, respectively (P = .006). Toxicity profiles were similar to those for the single agents.
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