Poster Presentations

Session Title: LIVER TUMORS b) CLINICAL (EPIDEMIOLOGY, DIAGNOSIS, MANAGEMENT)
Presentation Date: Apr 25, 2009

SORAFENIB FOR THE TREATMENT OF ADVANCED HEPATOCELLULAR CARCINOMA. FEASIBILITY AND SAFETY OUTSIDE RESEARCH TRIALS

M. Reig¹, A. Forner¹, J. Rimola², C. Rodriguez de Lope¹, C. Ayuso², J.M. Llovet¹, J. Bruix^1
1BCLC Group. Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPS, ²BCLC Group. Radiology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain

Background: Sorafenib (an oral tyrosine kinase inhibitor that blocks the Raf/MEK/ERK pathway and the receptor for VEGFR 2 and PDGFR-beta) has been shown to improve survival of patients with advanced Hepatocellular Carcinoma (HCC). However, presence of comorbidities and toxicity may not reproduce the data of the pivotal SHARP trial.
Aim: To assess the applicability of sorafenib in patients with advanced HCC within a referral liver cancer centre and to establish the safety and tolerance of treatment outside a prospective trial.
Methods: Between October 2007 and October 2008 we prospectively registered the feasibility and tolerance of sorafenib in patients with advanced HCC, liver function should fit into Child-Pugh A-B up to 7 points. Uncontrolled arterial hypertension and/or unstable arterial disease were taken as formal contraindication.
Results: 120 patients had indication for Sorafenib treatment, but 53 presented contraindication for the drug. Median age of the patients in treatment was 63 years, 84% males, all cirrhotics (58,7% HCV+). 84% Child-Pugh A, BCLC stage was B in 60% and C in 40%. 49 of the patients needed dose modification at a median follow-up time of 26 days (range: 3-296): in 23 pts the dose was halved (median 28 days, range: 3-224) while in 26 pts the treatment was discontinued after a median of 18 days (range: 3-296). The cause or modification doses were: Hand-foot syndrome (27.4%), arterial hypertension (10%), performance status impairment (16%), acute pancreatitis in 5, 9% and other complains in the remaining. In 55% of the cases it was possible to return to reinitiate the therapy after controlling the adverse events. According to CTCAE (v 3.0) the grades of secondary effects were 79% I, 14% II, 6% III and less 1% grade IV.
Conclusion: Sorafenib treatment was feasible in 53% of the HCC patients evaluated for this option outside the trials. The majority of the events leading to dose modification are registered within the first 3 weeks. Hence, careful follow-up has to be established during the early treatment phase in order to detect and manage any adverse event and thus allow prompt recovery and potential return to conventional dosing.