Avastin for hepatocellular cancer – pro

The only proven potentially curative therapy for HCC remains surgical, either hepatic resection or liver transplantation, and patients with single small HCC ( 5 cm) or up to three lesions 3 cm should be referred for assessment for these treatment modalities. However, these treatments cannot be applied in metastatic disease.  In regard to chemotherapy, palliative systemic therapy with doxorubicin (Adriamycin) has been considered a standard of therapy with response rates of 10 to 20 % with usually partial responses, but with no evidence for survival benefit. As doxorubicin is metabolized by the liver, the dose needs to be reduced or discontinued with rising bilirubin levels and liver dysfunction. Single agent 5-flurouracil, capecitabine or gemcitabine may be better tolerated in such a situation but still with low objective response rates. Combination chemotherapy regimens results in higher response rates but at increased toxicities and unproven survival benefits, and are not usually recommended.

A recent guideline states: “Systemic chemotherapy with standard agents has a poor response rate and should only be offered in the context of trials of novel agents (evidence grade I, recommendation grade A). “

Recent data for bevacizumab in HCC indicate that this agent can be administered safely in carefully selected HCC patients and has demonstrated modest clinical activity ]. Schwartz et al. reported their preliminary experience using single-agent bevacizumab in HCC in a phase I study. Of the first 24 patients treated, partial responses were seen in two patients, and SD of more than 4 months’ duration was noted in 17 patients; the median time to progression in these 24 patients was 6.4 months. A phase II study using bevacizumab in combination with gemcitabine and oxaliplatin (GEMOX-B) in advanced HCC showed that this regimen had moderate antitumor activity in HCC, with an overall response rate of 20% in evaluable patients and an additional 27% of patients with SD [96]. The median overall survival time was 9.6 months, and the median PFS time was 5.3 months, with the PFS rates at 3 and 6 months approaching 70% and 48%, respectively. The most common treatment-related grade 3–4 toxicities included leukopenia/neutropenia, transient elevation of transaminases, hypertension, and fatigue.

A recent TEC assessment did not recommend Avastin for hepatocellular carcinoma.

Avastin with erlotinib is not recommended by guidelines. It is in a study: Bevacizumab and Erlotinib or Sorafenib as First-Line Therapy in Treating Patients With Advanced Liver Cancer, NCT00881751. Researchers from the M. D. Anderson Cancer Center have reported that the combination of two targeted therapies—Avastin® (bevacizumab) and Tarceva® (erlotinib)—has anticancer activity in patients with advanced hepatocellular cancer (HCC) and warrants further study. Several recent phase II studies suggested that this combination has merit but requires more study. The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC. Current correlatives may help to guide future HCC studies.


Padhya, Kunjali T.; Marrero, Jorge A.; Singal, Amit G. Recent advances in the treatment of hepatocellular carcinoma

CURRENT OPINION IN GASTROENTEROLOGY  Volume: 29   Issue: 3   Pages: 285-292 , MAY 2013

 Fang, Ping; Hu, Jin-hua; Cheng, Zhi-gang; et al. Efficacy and Safety of Bevacizumab for the Treatment of Advanced Hepatocellular Carcinoma: A Systematic Review of Phase II Trials  Volume: 7   Issue: 12    19 2012

Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005 Nov;42(5):1208-36. [322 references]

Siegel AB, Cohen EI, Ocean A, et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol. 2008;26(18):2992-2998.

Off-Label Uses of Bevacizumab: Renal Cell Carcinoma and Other Miscellaneous Non-Colorectal Cancer Indications BCBS Assessment Program Volume 21, No. 9  October 2006

Zhu, Andrew X.
Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?
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Thomas MB, Morris JS, Chadha R et al. Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. Journal of Clinical Oncology [early online publication]. January 12, 2009.

S D Ryder Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults Gut 2003;52:iii1

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