Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma.
BACKGROUND
The hypervascular nature of hepatocellular carcinoma (HCC) is well characterized. Recent data have suggested that thalidomide possesses antiangiogenic and immunomodulatory activity. Therefore, the authors initiated a study to assess the efficacy and toxicity of thalidomide in patients with advanced HCC as primary and secondary endpoints, respectively.


METHODS
Inclusion criteria were unresectable HCC with bidimentionally measurable disease, age > or = 18 years, Eastern Cooperative Oncology Group performance status < or = 2, and adequate organ function. Thalidomide was administered at a starting dose of 200 mg per day in a 100-mg-per-week dose escalation regimen, up to the maximum tolerated dose or to 800 mg per day. Toxicity was monitored according to the National Cancer Institute Common Toxicity Criteria.


RESULTS
Twenty-six of 27 patients were eligible and assessable for toxicity and response. A median daily dose of 300 mg was achieved. One patient experienced near-complete recovery of alpha-fetoprotein levels and a partial radiographic response on computed tomography. Two patients had stable disease during the 16-week study period. The median duration of progression-free survival was 42 days. The overall median survival was 123 days. Fatigue and somnolence were the most common side effects, occurring in 81% and 62% of patients, respectively. No Grade 4 hematologic toxicity was observed. Three patients experienced Grade 4 hepatic toxicity (namely, hyperbilirubinemia).


CONCLUSIONS
With gradual dose escalation, thalidomide was tolerated in most patients with advanced HCC. However, treatment with thalidomide alone was associated with only a modest response in the treatment of HCC.
Lin
Albert Y
AY
Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128, USA. albert.lin@hhs.co.santa-clara.ca.us
Brophy
Nathalie
N
Fisher
George A
GA
So
Sam
S
Biggs
Christopher
C
Yock
Torunn I
TI
Levitt
Lee
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D013792:Thalidomide