Efficacy, safety and impact on quality of life of Sorafenib in elderly patients with advanced Hepatocellular carcinoma. Preliminary results of a Phase II study

Introduction: Sorafenib is the only systemic therapy that has prolonged the median survival and time to progression in patients with advanced hepatocellular carcinoma. Methods: The primary aim of this open prospective non-randomized phase II study was to assess efficacy and safety of sorafenib in a selected population of elderly patients with advanced hepatocellular carcinoma not previously treated. Secondary aims included quality of life (QoL) assessment using SF-36 questionnaire and changes of serum IL-6. All patients underwent multidimensional geriatric assessment (MGA) and accordingly were assigned to 3 different categories: fit, intermediate and frail. Scheduled sorafenib dose was 800 mg/day until disease progression or unacceptable toxicity. Efficacy was assessed every 3 months and defined as objective clinical response (RECIST) and disease-control rate (DCR), i.e. the percentage of patients who had a best-response (complete response, CR, or partial response, PR, or stable disease, SD) maintained for at least 28 days. Results: From January to November 2008 14 patients (M/F ratio, 12:2; mean age 70.7±3.1 years; range, 66−76) were enrolled and 13 were evaluable after 3 months: 28.6% had ECOG PS 0, 57.1% PS 1, and 14.3% PS 2. According to MGA, 3 patients were fit, 8 intermediate and 3 frail. At 3-month evaluation no CR/PR, 8/13 (61.5%) SD, 5/13 (38.5%) PD were observed. DCR was 75.0% (6/8 patients). The toxicity was moderate and the worst was grade 3: hand-foot and skin reactions (30.7%), hypertension (15.4%), diarrhea (30.7%), nausea and vomiting (7.7%), asthenia (15.4%). The treatment was interrupted for a mean of 9 days (range 4−19) due to toxicities in 84.6% of patients and restarted at a reduced dosage (400 mg/day) which was well tolerated. The mean dosage was 552 mg/day. QoL improved globally and in particular for: pain, energy, physical activity and patient perception of self-health status. Serum IL-6 were high at enrolment and did not change thereafter. At Novembrer 2008, 10/13 patients are alive. Conclusion: In elderly cancer patients with advanced hepatocellular carcinoma sorafenib demonstrated a good DCR, a moderate toxicity at 800 mg/day, an optimal acceptability at 400 mg/day and a significant improvement of quality of life