体外化疗药物敏感实验对指导原发性肝癌个体化疗的临床意义

背景与目的:肝细胞癌(肝癌)化学治疗效果差。为了提高化疗效果,本研究采用体外化疗敏感实验——三磷酸腺苷肿瘤化疗药物敏感实验(adenosinetriphosphatetumorchemosensitivityassay,ATP鄄TCA)系统评估化疗药物,并利用该系统指导肝癌患者临床个体化疗。方法:获取50个原发性肝癌手术标本,采用ATP鄄TCA系统评估5鄄氟尿嘧啶(5鄄fluorouracil,5鄄FU)、丝裂霉素(mitomycin,MMC)、顺铂(cisplatin,DDP)、草酸铂(oxaliplatin,OXA)、表阿霉素(epirubicin,EPI)、健择(gemcitabine,GEM)、伊立替康(irinotecan,CPT鄄11)、足叶乙甙(etoposide,VP鄄16)和泰素(paclitaxel,PTX)等化疗药物;23例肝癌患者术后接受ATP鄄TCA系统指导临床化疗,同时以20例接受手术及常规治疗的肝癌患者作为对照,观察162周临床疗效。结果:ATP鄄TCA系统结果可评估率为90.8%。肝癌细胞对各种化疗药物中鄄高度敏感率分别为:泰素46%、伊立替康44%、健择36%、丝裂霉素14%、表阿霉素12%、顺铂8%、足叶乙甙6%、草酸铂6%以及5鄄氟尿嘧啶4%;临床结果:临床研究观察终点ATP鄄TCA组与对照组比较,PR、CR、SD及观察期内患者死亡率两组之间无显著性差异;然而对照组有较高病情进展发生率(60.00%vs.13.04%,P=0.003);ATP鄄TCA组较对照组在总病情缓解率(60.86%vs.30.00%,P=0.043)、平均手术后总生存期(78.91周vs.27.21周,P=0.006)及手术后无疾病进展生存期(30.52周vs.4.78周,P=0.005)方面表现出明显优势。结论:ATP鄄TCA系统可以成功用于评估肝癌标本。泰素、伊立替康和健择有较高的体外抗肝癌活性。ATP鄄TCA系统指导肝癌个体化疗有可能提高患者无疾病进展生存期和总生存期。

Application of adenosine triphosphate tumor chemosensitive assay system to individual chemotherapy for hepatocellular carcinoma

BACKGROUND & OBJECTIVE: Present chemotherapy for hepatocellular carcinoma (HCC) is not effective. To improve the effect of chemotherapy, in vitro chemo-drug sensitive testing system, adenosine triphosphate tumor chemosensitive assay (ATP-TCA) system, was used to evaluate efficacies of chemotherapeutic drugs, and to guide clinical individual chemotherapy for HCC patients. METHODS: ATP-TCA system was applied to test efficacies of 5-fluorouracil (5-FU), mitomycin (MMC), cisplatin (DDP), oxaliplatin (OXA), epirubicin (EPI), gemcitabine (GEM), irinotecan (CPT-11), etoposide (VP-16), and paclitaxel (PTX) on 50 HCC samples. Twenty-three HCC patients received ATP-TCA-directed chemotherapy (ATP-TCA group)? 20 HCC patients received surgery and routine treatments (control group). Clinical outcomes of these patients were observed for 162 weeks. RESULTS: The assessable rate of ATP-TCA result is 90.8%. In the 50 samples, the sensitive (moderate to high degree) rates were 46% to PTX, 44% to CPT-11, 36% to GEM, 14% to MMC, 12% to EPI, 8% to DDP, 6% to VP-16, 6% to OXA, and 4% to 5-FU, respectively. In clinical trial, at the research end-point, no significant differences were found in partial remission (PR), complete remission (CR), stable disease (SD), and mortality between ATP-TCA group and control group (P > 0.05), but progression disease (PD) rate was significantly higher in control group than in ATP-TCA group (60.00% vs.13.04%, P=0.003); significant differences were found in overall response rate (ORR) (60.86% vs. 30.00%, P =0.043), overall survival (OS) (78.91 weeks vs. 27.21 weeks, P=0.006), and progress-free survival (PFS) (30.52 weeks vs. 4.78 weeks, P=0.005) between ATP-TCA group and control group. CONCLUSIONS: ATP-TCA system might be useful in evaluating the efficacy of chemotherapeutic drugs on HCC samples, and in planning individualized chemotherapy regimen for HCC patients. PTX, CPT-11 and GEM might be potential drugs for the treatment of HCC. ATP-TCA-guided chemotherapy might prolong survival time of HCC patients.