title: Clinical efficacy of metronomic chemotherapy after cool-tip radiofrequency ablation in the treatment of hepatocellular carcinoma.
abstract: OBJECTIVE
  Anti-angiogenic agents have shown promise for treating advanced hepatocellular carcinoma (HCC), and the primary mechanism of low-dose metronomic chemotherapy using traditional cytotoxic drugs is anti-angiogenic. This study evaluated the efficacy of metronomic capecitabine and thalidomide after cool-tip radiofrequency ablation (RFA), relative to RFA alone, for treating patients with HCC.
  
  
  METHODS
  Patients with HCC were randomly apportioned to a test group (n = 22) receiving metronomic chemotherapy with capecitabine and thalidomide after RFA, or a control group (n = 28) receiving RFA only. Serum circulating endothelial cells (CECs) and vascular endothelial growth factor (VEGF) were measured in all patients before and 1 month after RFA treatment. Enhanced computed tomography or ultrasound imaging was performed to evaluate efficacy during 12 months of follow-up. The treatment groups were further stratified as HCC within or outside the Milan criteria for transplantation.
  
  
  RESULTS
  One month post-treatment, the tumour response rate (TRR), including complete response and partial response rate, of the test and control groups was statistically similar. At 12 months, the TRR of the test group (68.2%) was significantly higher than that of the control group (35.7%). In the test group, the TRR of patients whose tumour burdens were outside the Milan criteria was significantly higher than that of the control group. One month post-treatment, CECs and VEGF levels of the test group were significantly lower than baseline, while those of the control group were significantly higher. At the end of the 12-month follow-up, there was a progression-free survival (PFS) benefit of 2 months in the test group.
  
  
  CONCLUSIONS
  Metronomic capecitabine and thalidomide after RFA significantly reduced recurrence of HCC and extended PFS, especially for HCC outside the Milan criteria, perhaps via reduction of serum CECs and VEGF levels and inhibition of tumour angiogenesis.
authors.affiliation: a Department of Geriatrics , Affiliated Hospital of Hainan Medical College , Haikou and.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Wang-Yuan
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Jiang-Zheng
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Yan-Da
authors.initials: YD
authors.lastname: Lu
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Xin-Bao
authors.initials: XB
authors.lastname: Hao
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hong
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Lei
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: He
authors.affiliation: b Department of Clinical Oncology , Hainan Medical College Cancer Institute, Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Mei-zhu
authors.initials: MZ
authors.lastname: Huang
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000069287:Capecitabine / Q000008:administration & dosage* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D042783:Endothelial Cells; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D008297:Male; D008875:Middle Aged; D013792:Thalidomide / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D000069287:Capecitabine
keywords: Hepatocellular carcinoma; metronomic chemotherapy; radiofrequency ablation; tumour angiogenesis