Chemotherapy for liver cancer – pro

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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Zhu AX, Blaszkowsky LS, Ryan DP, et al. Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma. J Clin Oncol. Apr 20 2006;24(12):1898-903.

Llovet J, Ricci S, Mazzaferro V, et al. Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a phase III randomized placebo-controlled trial (SHARP trial). J Clin Oncol. 2007;25(suppl):962s(abstract LBA1).

Faivre S, Raymond E,Douillard J, et al. Assessment of safety and drug-induced tumor necrosis with sunitinib in patients (pts) with unresectable hepatocellular carcinoma. J Clin Oncol. 2007;25:149s Abstract 3546.

Rougier P, Mitry E, Barbare JC, et al. Hepatocellular carcinoma (HCC): an update. Semin Oncol. Apr 2007;34(2 Suppl 1):S12-20.

Abou-Alfa GK, Johnson P, Knox JJ, Capanu M, Davidenko I, Lacava J, Leung T, Gansukh B, Saltz LB. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA. 2010 Nov 17;304(19):2154-60.

Yeo W, Mok TS, Zee B, et al. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst. 2005;97:1532–1538

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