title: Efficacy and safety of metronomic chemotherapy for patients with advanced primary hepatocellular carcinoma with major portal vein tumor thrombosis.
abstract: OBJECTIVE
  Low-dose metronomic chemotherapy involves the frequent administration of comparatively low doses of cytotoxic agents with no extended breaks, and it may be as efficient as and less toxic than the conventional maximum tolerated dose therapy. This study evaluated the feasibility and therapeutic efficacy of metronomic chemotherapy in patients with advanced hepatocellular carcinoma (HCC) with major portal vein thrombosis (PVT).
  
  
  METHODS
  Thirty consecutive HCC patients with major PVT with or without extrahepatic metastasis were prospectively allocated to metronomic chemotherapy consisting of epirubicin being infused through the correct hepatic artery at a dose of 30 mg/body surface area (BSA) every 4 weeks, and cisplatin (15 mg/BSA) and 5-fluorouracil (50 mg/BSA) every week for 3 weeks, with intervening 1 week breaks. The treatment response was assessed using response evaluation criteria in solid tumors (RECIST).
  
  
  RESULTS
  In total, 116 cycles of metronomic chemotherapy were administered to the 30 patients, with a median of 3 cycles given to individual patients (range, 1-15 cycles). Six patients (20.0%) achieved a partial response and six patients (20.0%) had stable disease. The median time to disease progression and overall survival were 63 days (range, 26-631 days) and 162 days (95% confidence interval; range, 62-262 days), respectively. Overall survival was significantly associated with baseline alpha-fetoprotein level (P=0.001) and tumor response (P=0.005). The baseline alpha-fetoprotein level was significantly associated with the disease control rate (P=0.007). Adverse events were tolerable and managed successfully with conservative treatment.
  
  
  CONCLUSIONS
  Metronomic chemotherapy may be a safe and useful palliative treatment in HCC patients with major PVT.
authors.affiliation: Department of Internal Medicine and Medical Research Institute, Pusan National University College of Medicine, Busan, Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Woo
authors.forename: Jun Mo
authors.initials: JM
authors.lastname: Youn
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jang
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Cha
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Kim
authors.forename: Ho Jong
authors.initials: HJ
authors.lastname: Chun
authors.forename: Byung Gil
authors.initials: BG
authors.lastname: Choi
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Seoung Kew
authors.initials: SK
authors.lastname: Yoon
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D011379:Prognosis; D014057:Tomography, X-Ray Computed; D020246:Venous Thrombosis / Q000150:complications / Q000175:diagnosis*; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D000509:alpha-Fetoproteins; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil