title: Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma: an open-label Phase II feasibility study.
abstract: OBJECTIVE
  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/m(2) 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).
  
  
  CONCLUSIONS
  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.
authors: Combined Military Hospital and Medical College, Lahore Cantt, Pakistan. Electronic address: naeemnaqi@hotmail.com.
authors: Naeem
authors: N
authors: Naqi
authors: Mayo Hospital, King Edward Medical University, Lahore, Pakistan.
authors: Shaharyar
authors: S
authors: Ahmad
authors: Institute of Nuclear Medicine and Oncology, Lahore, Pakistan.
authors: Sohail
authors: S
authors: Murad
authors: Combined Military Hospital, Rawalpindi, Pakistan.
authors: Javaid
authors: J
authors: Khattak
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D003710:Demography; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D000093542:Gemcitabine