Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: A large multicenter AGEO study

Background & Aims The current standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. This drug is effective but generally does not induce tumor shrinkage and other treatment options are still needed. Methods This retrospective multicenter study included all consecutive patients with advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and 2010. Survival curves were drawn with the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analyses were used to evaluate prognostic factors. Results Two hundred four consecutive patients were treated with GEMOX (median age, 60 years; men, 86%; underlying cirrhosis, 76%). Grade 3–4 toxicity was observed in 44% of the patients (thrombocytopenia 24%, neutropenia 18%, diarrhea 14%, neurotoxicity 12%) leading to treatment discontinuation in 16% of the cases. The overall response and disease control rates were 22% (95% CI, 16–27) and 66% (95% CI, 59–72), respectively. No clinical or biological factors were associated with the treatment response, and 8.5% of the patients were subsequently eligible for curative-intent therapies after downstaging. Median PFS, TTP, and OS were 4.5 (95% CI, 4–6), 8 (95% CI, 6–11), and 11 months (95% CI, 9–14), respectively. In multivariate analysis, gender (p = 0.03), underlying cirrhosis (p = 0.01), CLIP score (p = 0.03), and response to GEMOX (p <0.0001) were independently associated with OS. Conclusions This large study confirms that GEMOX is effective with manageable toxicity in patients with advanced HCC. Tumor responses permitted potentially curative treatment that was not initially feasible in a significant proportion of patients. The current standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. This drug is effective but generally does not induce tumor shrinkage and other treatment options are still needed. This retrospective multicenter study included all consecutive patients with advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and 2010. Survival curves were drawn with the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analyses were used to evaluate prognostic factors. Two hundred four consecutive patients were treated with GEMOX (median age, 60 years; men, 86%; underlying cirrhosis, 76%). Grade 3–4 toxicity was observed in 44% of the patients (thrombocytopenia 24%, neutropenia 18%, diarrhea 14%, neurotoxicity 12%) leading to treatment discontinuation in 16% of the cases. The overall response and disease control rates were 22% (95% CI, 16–27) and 66% (95% CI, 59–72), respectively. No clinical or biological factors were associated with the treatment response, and 8.5% of the patients were subsequently eligible for curative-intent therapies after downstaging. Median PFS, TTP, and OS were 4.5 (95% CI, 4–6), 8 (95% CI, 6–11), and 11 months (95% CI, 9–14), respectively. In multivariate analysis, gender (p = 0.03), underlying cirrhosis (p = 0.01), CLIP score (p = 0.03), and response to GEMOX (p <0.0001) were independently associated with OS. This large study confirms that GEMOX is effective with manageable toxicity in patients with advanced HCC. Tumor responses permitted potentially curative treatment that was not initially feasible in a significant proportion of patients.