title: Gemcitabine and oxaliplatin as second-line treatment in patients with hepatocellular carcinoma pre-treated with sorafenib.
abstract: Some patients with advanced hepatocellular carcinoma (HCC) progressing under sorafenib remain eligible for further systemic therapy. Little is known on the feasibility of systemic treatment beyond sorafenib in this setting. Consecutive HCC patients pre-treated with sorafenib received gemcitabine 1,000 mg/m² and oxaliplatin 100 mg/m² every 14 days. Exclusion criteria included Child C cirrhosis, PS≥3, creatinine clearance<20 ml/min, albumin<25 g/L and bilirubin>54 μmol/L. Pre-treatment body composition was evaluated by CT scan to detect muscle wasting (sarcopenia). The primary evaluation criterion was safety. Secondary evaluation criteria were response rate, and progression-free (PFS) and overall survival (OS). Eighteen patients (median age: 64 years, range 25-77) received a total of 90 cycles (median per patient: 4, range 1-16). Eight patients (44.4 %) had a PS of 2, 5 (27.8%) had Child-Pugh B cirrhosis and 13 (72.2%) had a CLIP score>3. The most frequent toxicities were thrombocytopenia (grade 2-4: n=7, 38.9%) and peripheral neuropathy (grade 2-3: n=7, 38.9%). The overall response rate was 18.8% (95% CI: 0-37.9), and another 18.8 % of patients had stable disease. The median PFS and OS were 3.2 (95% CI: 2.3-3.9) and 4.7 (95% CI: 3.8-8.1) months, respectively. Overall survival was significantly longer in patients without sarcopenia [10.0 months (95% CI: 7.0-13.8) vs. 3.0 months (95 % CI: 2.5-3.9), p<0.001] and in patients with an ECOG PS<2 [8.1 months (95% CI: 7.0-13.8) vs. 3.8 months (95% CI: 2.5-3.9), p=0.017]. In our experience, gemcitabine-oxaliplatin was feasible and had detectable clinical activity in HCC patients pre-treated with sorafenib. Further studies are needed to confirm these findings.
authors.affiliation: Department of Medical Oncology, Centre for Research on Angiogenesis Inhibitors (CERIA), Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, 27, rue du faubourg Saint Jacques, 75014, Paris, France. olivier.mir@cch.aphp.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
authors.forename: Romain
authors.initials: R
authors.lastname: Coriat
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boudou-Rouquette
authors.forename: Stanislas
authors.initials: S
authors.lastname: Ropert
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Durand
authors.forename: Anatole
authors.initials: A
authors.lastname: Cessot
authors.forename: Vincent
authors.initials: V
authors.lastname: Mallet
authors.forename: Philippe
authors.initials: P
authors.lastname: Sogni
authors.forename: Stanislas
authors.initials: S
authors.lastname: Chaussade
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D000093542:Gemcitabine