Efficacy and safety of sorafenib–gemcitabine combination therapy in advanced hepatocellular carcinoma: An open-label Phase II feasibility study

• Published in: Hematology/oncology and stem cell therapy 2014-03, Vol.7 (1), p.27-31
• Main Authors: Naqi, Naeem, Ahmad, Shaharyar, Murad, Sohail, Khattak, Javaid
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Demography; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Feasibility Studies; Female; Hematology, Oncology and Palliative Medicine; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Niacinamide - adverse effects; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; Treatment Outcome
• ISSN: 1658-3876
• DOI: 10.1016/j.hemonc.2013.11.003

Abstract Purpose Sorafenib is considered a standard of care in advanced hepatocellular carcinoma (HCC). Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile may prove beneficial in advanced HCC. The primary objective was to evaluate the efficacy and safety of a sorafenib and gemcitabine combination in patients with advanced HCC. Methods This was a non-randomized, open-label, single-arm, multi-centric Phase II study conducted in Pakistan where 30 treatment-naive patients aged between 26 and 73 years with Child–Pugh score A or B were treated with sorafenib (400 mg oral) twice daily for 16 weeks along with gemcitabine (1000 mg/m2 intravenous) administered on day 1 and day 8 of a four-week cycle for 16 weeks. Results Of the 18 patients (60%) who completed all four cycles of treatment, eight patients had stable disease, two had partial response, and eight had progressive disease. There was no complete response. The most common (⩾10% patients) treatment-emergent adverse events were gemcitabine-related thrombocytopenia (40%) followed by sorafenib-related hand–foot skin reaction and anorexia (33% each). Conclusion The efficacy of sorafenib gemcitabine combination therapy is similar to the sorafenib alone treatment. However, frequent dose adjustments due to gemcitabine-related toxicities, delays, and corrective treatments make this combination therapy unsafe in the treatment of advanced HCC.