[Application of adenosine triphosphate tumor chemosensitive assay system to individual chemotherapy for hepatocellular carcinoma].
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)û 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.
Chen
Tao
T
Department of General Surgery, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China. chent9812@yahoo.com
Chu
Zhong-Hua
ZH
Liu
Jian-Ping
JP
Wang
Jie
J
Zhao
Hai-Yan
HY
Ou
Qing-Jia
QJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018572:Disease-Free Survival; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D011184:Postoperative Period; D012074:Remission Induction; D012680:Sensitivity and Specificity; D015996:Survival Rate; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D000077146:Irinotecan; D000255:Adenosine Triphosphate; D017239:Paclitaxel; D002166:Camptothecin; D000093542:Gemcitabine