Combination of topotecan and oxaliplatin in inoperable hepatocellular cancer patients
Combination of topotecan and oxaliplatin in inoperable hepatocellular cancer patients
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DOI：
10.1097/00000421-200204000-00021
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发表时间：
2002-04-01
影响因子：
2.6
通讯作者：
Goldwasser, F
中科院分区：
文献类型：
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作者：
Alexandre, J;Tigaud, JM;Goldwasser, F
不可切除的肝细胞癌（UHCC）被认为是一种化疗耐药疾病，而且，由于肝脏是这种疾病的基础，它降低了对抗癌药物的耐受性。Topotecan在每3周使用5天的UHCC中显示出一定的临床活性，但由于严重的血液毒性而受到限制。奥沙利铂是一种二氨基环己烷-铂，与拓扑替康具有体外协同作用。13例UHCC患者每21天接受拓扑替康（0.5-1.5 mg/m(2)/d，第1-5天）和奥沙利铂（85-110 mg/m(2)/d，第1天）。所有患者肝脏生物学指标均在正常范围内；我在世界卫生组织的绩效等级低于2。7例患者之前接受过化疗。9名无肝硬化的患者接受了中位数为6个周期（范围：3-12）的治疗。主要的剂量限制性毒性是在3例患者和4%的周期中观察到严重的血小板减少。观察到1例客观反应和8例稳定。相反，在接受中位数2.5周期（范围：1-6）的4例肝硬化患者中，2例患者和25%的周期发生严重血小板减少。3例病情进展，1例病情稳定。整体。中位稳定持续时间为27周（范围：16-97周）。7例接受I mg/m(2)/d或更多拓扑替康治疗的患者中有4例出现严重毒性。这些结果支持在非肝硬化的UHCC患者中开展该联合疗法的11期研究。进一步研究的推荐剂量应为拓扑替康0.5 mg/m(2)/d至0.75 mg/m(2)/d，奥沙利铂85 mg/m(2)。
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; I I 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 I mg/m(2)/d or more topotecan experienced severe toxicity. These results warrant a phase 11 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.