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/m(2) /d days 1-5) and oxaliplatin (85-110 mg/m(2) /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/m(2) /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/m(2) /d to 0.75 mg/m(2) /d of topotecan with 85 mg/m(2) of oxaliplatin.
Alexandre
Jérôme
J
Service de cancérologie, Hôpital Paul Brousse, Villejuif, France.
Tigaud
Jean-Marie
JM
Gross-Goupil
Marine
M
Gornet
Jean-Marie
JM
Romain
Didier
D
Azoulay
Daniel
D
Misset
Jean-Louis
JL
Goldwasser
François
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D019772:Topotecan / Q000008:administration & dosage
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019772:Topotecan