Combination of Topotecan and Oxaliplatin in Inoperable Hepatocellular Cancer Patients

Unresectable hepatocellular carcinoma (UHCC) is considered a chemoresistant disease. Moreover, because the liver underlies the disease, it decreases the tolerance to anticancer agents. Topotecan has shown some clinical activity in UHCC using the 5 days every 3 weeks schedule but is limited by severe hematotoxicity. Oxaliplatin is a diamino-cyclo-hexane-platin that exhibits in vitro synergy with topotecan. Thirteen UHCC patients received topotecan (0.5–1.5 mg/m2/d days 1–5) and oxaliplatin (85–110 mg/m2/d, day 1) every 21 days. All patients had liver biology within normal limits; 11 had World Health Organization performance status less than 2. Seven patients had received previous chemotherapy. Nine patients without cirrhosis received a median number of six cycles (range: 3–12). The main dose-limiting toxicity was severe thrombocytopenia observed in three patients and 4% of cycles. One objective response and eight stabilizations were observed. Conversely, among 4 patients with cirrhosis receiving a median number of 2.5 cycles (range: 1–6), severe thrombocytopenia occurred in 2 patients and 25% of cycles. Three patients with progressive disease and one with stabilization were observed. Overall, the median duration of stabilizations was 27 weeks (range: 16–97 weeks). Four of seven patients treated with 1 mg/m2/d or more topotecan experienced severe toxicity. These results warrant a phase II study of this combination in noncirrhotic patients with UHCC. The recommended doses for further studies should be 0.5 mg/m2/d to 0.75 mg/m2/d of topotecan with 85 mg/m2 of oxaliplatin.