Viscum album is another therapeutic option for HCC in patients with cirrhosis, value of GP 73 Golgi protein as a marker

ABSTRACT

Hepatocellular carcinoma [HCC] is one of the most common cancers worldwide. Efficacy of available treatments remains disappointing. Mistletoe extract [Viscum album], a cytotoxic, immune stimulating and immune modulating agent has been tried by subcutaneous or intralesional route in the management of this disease. Is to evaluate the effect of viscum fraxini 2 in the management of advanced HCC in patients with liver cirrhosis not amenable for other therapeutic intervention and evaluate the value of the recently investigated GP 73 Golgi protein as a marker of such disease. 26 patients with advanced cirrhosis and HCC were subjected to investigation and treatment in this study. All patients provided a complete history and physical examination, including performance status, concurrent non-malignant diseases and therapy. Laboratory studies included a complete blood cell counts, differential count, biochemical liver and renal function tests, electrolyte, chest x-rays, a-fetoprotein, triphasic liver computed scan [CT] and Child class evaluation were performed before treatment. Immunoblot Analysis for GP73 was performed in all patients before and at end of follow up. 2 ampoules of viscum fraxini-2 were administered subcutaneously once weekly. Each ampoule is 15 mg extract of 20 mg mistletoe herb from ash tree, diluted in dinatrium-mono-hydrogen phosphate, ascorbic acid and water] which is equivalent to 10000 ng/ml injection ampoules. The study included 26 patients. They were 19 males and 7 females, aged 37-62 years with a mean of 50.58 +/- 7.51 years. Modified Child-Pugh stage A was found in 2 patients [7.7%], stage B in 14 patients [53.8%] and stage C in 10 patients [38.5%]. The diagnosis of HCC was based on marked elevation of alpha-fetoprotein level and imaging studies indicating advanced HCC in 19 patients [73.1%] and on fine-needle aspiration cytology of liver tumors in 7 patients [16.9%]. The median duration of treatment on viscum fraxini-2 is 16 months [range 4-24 months]. The mean GP protein signal intensities by Westernblot in all patients before and at end of follow up were 30.38 +/- 9.43 and 25.15 +/- 12.15 respectively with P < 0.001 [highly significant]. In those showing reduction of tumor size, it was 27.46 +/- 11.04 and 17.31 +/- 8.12 respectively with P < 0.001 [highly significant]. In those showing increase in the size of tumor it was 33.31 +/- 6.69 and 30.00 +/- 10.40 respectively with P< 0.01 [also highly significant]. According to conventional radiological response criteria, only 2 patients [7.7%] achieved complete response. Three patients [11.6%] achieved partial response. Sub-optimal response was detected in 8 [30.8%] patients. The remaining 13 cases [50%] showed progressive disease or early death. Eight patients [30.8%] died early before 12 months of follow up. At the time of analysis after 24 months, 9 [34.6%] patients remained alive including two patients with CR, the three patients with partial response, two patients with sub-optimal response and 2 patients with slowly progressive disease. The median survival time for patients who died during the two years of follow up [17 patients, 65.4%] was 11.88 +/- 4.7 months. The overall follow up period including those who were alive at the end of the second year was 16.5 +/- 7.16 month. There were no drug related discontinuation or toxic deaths. Viscum fraxini 2 produced complete response in 7.7% and partial response in 11.6% while suboptimal response in 30.8% of patients. Thus, some beneficial effect can be achieved in half of patients. From these results, we can conclude that the drug can be added at the moment to the drug list for the treatment of HCC. Being safe, simply administered by weekly injections, cheep and nearly of similar efficacy to other drugs; it can be used either alone or in combinations for long periods in the treatment of HCC. This study also added another evidence for the value of the recently investigated, GP73 Golgi protein, in the diagnosis and follow up of patients with liver cirrhosis who develop HCC during treatment