title: Thalidomide in the treatment of patients with hepatocellular carcinoma: a phase II trial.
abstract: BACKGROUND
  The treatment of patients with hepatocellular carcinoma (HCC) presents a major challenge, because associated cirrhosis limits the choice of chemotherapeutic agents. However, the abundant vascularity of HCC presents an attractive target for antiangiogenic therapy that potentially may be tolerated by cirrhotic patients. The current study was conducted to assess the antitumor activity, treatment tolerance, treatment-related toxicity, and patient survival after the administration of thalidomide in a Phase II trial.
  
  
  METHODS
  Thirty-seven HCC patients were accrued between March, 1999, and March, 2000. Initially, the dose of oral thalidomide was escalated from 400 mg per day during the first week to 1000 mg per day by the fifth week, delivering one-third of the dose in the morning and the remaining two-thirds of the dose in the evening prior to bedtime. Changes in the daily drug administration schedule were allowed based on tolerance. Response was assessed at 8-week intervals.
  
  
  RESULTS
  Thirty-two of 37 registered patients were evaluable for response. One patient had a partial response (PR), 1 patient had a minor response (MR), 10 patients had stable disease (SD) (31%; 95% confidence interval [95%CI], 16-51%), and 20 patients) (61%; 95%CI, 42-78%) had disease progression. The most commonly encountered toxicity was somnolence, with Grade 3-4 somnolence (>or= 4 hours of sleep during normal waking hours) in 9 patients (35%) and Grade 2 somnolence (<or= 3 hours) in 30% of patients. In fact, only 48% of patients tolerated a daily dose>800 mg if it was delivered at bedtime. Grade 3-4 skin reactions were observed in 20% of patients, and exfoliative dermatitis was observed in 1 responding patient. The overall median survival was 6.8 months.
  
  
  CONCLUSIONS
  With a 5% PR rate, a 5% MR rate, and a 31% SD rate, the results indicate that thalidomide mostly may offer HCC patients disease stabilization. It is possible that, at a different dosage, or combined with other chemotherapy agents, or with the use of a different thalidomide analogue, longer patient survival may be achieved. However, in view of the significant neurologic toxicity encountered among these commonly cirrhotic HCC patients, thalidomide monotherapy at the high doses studied cannot be recommended for the treatment of HCC.
authors.affiliation: Cancer Research and Treatment Center, The University of New Mexico, Albuquerque, New Mexico 87131, USA. yzpatt@salud.unm.edu
authors.forename: Yehuda Z
authors.initials: YZ
authors.lastname: Patt
authors.forename: Manal M
authors.initials: MM
authors.lastname: Hassan
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lozano
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Nooka
authors.forename: Isaac I
authors.initials: II
authors.lastname: Schnirer
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013792:Thalidomide / Q000009:adverse effects*
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide