Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC)

Abstract

BACKGROUND. New systemic therapies are needed to improve the prognosis of patients with advanced-stage hepatocellular carcinoma (HCC). In a Phase II trial involving previously untreated patients with advanced HCC, the more favorable schedule from a previous pilot study was evaluated. METHODS.Thirty-four patients with previously untreated advanced-stage HCC were prospectively enrolled. The GEMOX regimen consisted of gemcitabine 1000 mg/m 2 on Day 1 and oxaliplatin 100 mg/m 2 on Day 2. The treatment was repeated every 2 weeks until disease progression or limiting toxicity.RESULTS. Thirty-two patients were assessable for efficacy and 33 for toxicity. In all, 323 treatment cycles were administered. No toxic deaths occurred. Hematological grade 3-4 toxicity consisted of thrombocytopenia (27% of patients) and neutropenia (24%), including 2 febrile neutropenia and anemia (9%). Grade 3 oxaliplatin-induced neurotoxicity was observed in 3 (9%) patients. The overall response rate was 18% (95% confidence interval [CI]: 8-34) and disease stabilization was observed in 58% of patients (including 5 minor responses), giving a disease control rate of 76%. Median progression-free and overall survival times were, respectively, 6.3 months (95% CI: 4.3-10.1 months) and 11.5 months (95% CI: 8.5-14.3 months). Treatment was significantly more effective in patients with nonalcoholic cirrhosis than in those with alcoholic cirrhosis. CONCLUSIONS.The GEMOX regimen seems to be well tolerated and active in advanced HCC, especially in patients with underlying nonalcoholic liver disease.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…Many small-scale trials of combining MTT with cytotoxic chemotherapy have been reported [385][386][387][388][389]. However, the treatment efficacy in terms of tumor response rate and patient survival were similar to those reported for the cytotoxic regimens alone (Table 3) [372,[375][376][377][378][379][380][381][382]. A second approach is to combine MTT targeting different molecular pathways.…”

“…The most common grade 3-4 toxicity was myelosuppression, which occurred in 10-40% of the patients. Combination regimens, such as cisplatin/IFN/doxorubicin/ fluorouracil (PIAF), gemcitabine/oxaliplatin (GEMOX), or capecitabine/oxaliplatin (XELOX), can increase the objective response rate to approximately 20% but at the expense of increased treatment-related toxicities [382,383]. Therefore, cytotoxic chemotherapy can be used with caution only in selected patients with advanced HCC.…”

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

“…Although GEMOX was well-tolerable with the most common grade 3/4 toxicities of thrombocytopenia (27%) and neutropenia (24%) in patients with advanced HCC, the clinical outcome was not impressive with ORR of 18% (n=6) in a phase II study (44). Interestingly, all the objective responses were observed in patients with nonalcoholic underlying liver disease (6/21) but not with alcoholic liver disease (0/13).…”

Hepatocellular carcinoma treatment strategies – a case-based review

“…The gemcitabine plus oxaliplatin (GEMOX) regimen appeared to be the most promising, based on its lack of renal and hepatic toxicity in patients with underlying cirrhosis and its interesting efficacy in phase II trials [95][96][97] . The largest multicenter study suggested that GEMOX is effective with an acceptable profile of safety; the induced tumor response allowed a secondary local therapy option that was not initially feasible in a significant proportion of patients, which suggests that it could be indicated as a first line treatment for patients who may particularly benefit from tumor downsizing [2] .…”