title: A phase I/II trial of capecitabine combined with peginterferon α-2a in Patients with sorafenib-refractory advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon α-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II).
  
  
  METHODS
  Capecitabine was administered daily on days 1-14, while peginterferon α-2a was administered on days 1, 8, and 15. The cycle was repeated every 21 days. The patients were scheduled to receive capecitabine [mg/(m(2)∙day)] and peginterferon α-2a (μg/week) at 3 dose levels in phase I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3), respectively.
  
  
  RESULTS
  A total of 30 patients were enrolled. The recommended dose was level 3. Among the 24 patients receiving the drug at the recommended dosage, 2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42 %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median time to progression and overall survival were 3.0 months and 7.2 months, respectively. The most common toxicities were decreased white blood cell (88 %), neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment because of severe adverse events.
  
  
  CONCLUSIONS
  Capecitabine at 2000 mg/(m(2)∙day) combined with peginterferon α-2a (90 μg/week) exhibited moderate, albeit manageable, toxicity and was declared as the recommended phase II dose. Further research is required to refine the efficacy of this combination.
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Sadahisa
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ooka
authors.forename: Naoya
authors.initials: N
authors.lastname: Kanogawa
authors.forename: Tenyu
authors.initials: T
authors.lastname: Motoyama
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Suzuki
authors.forename: Akinobu
authors.initials: A
authors.lastname: Tawada
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kanai
authors.forename: And Osamu
authors.initials: AO
authors.lastname: Yokosuka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D000077157:Sorafenib
chemical_list: D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011994:Recombinant Proteins; D003841:Deoxycytidine; D009536:Niacinamide; D011092:Polyethylene Glycols; D000069287:Capecitabine; D000077157:Sorafenib; C100416:peginterferon alfa-2a; D005472:Fluorouracil
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