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Am J Clin Oncol. 2008 Feb;31(1):84-8. doi: 10.1097/COC.0b013e3181131db9.

Phase II study of imatinib in unresectable hepatocellular carcinoma.

Author information

  • 1Department of Medicine, Santa Clara Valley Medical Center, 751 S. Bascom Avenue, San Jose, CA 95128, USA. albert.lin@hhs.co.santa-clara.ca.us

Abstract

BACKGROUND:

The expression of platelet-derived growth factor, a potent mitogen, and its receptor both in tissue and serum correlate with the severity of liver cirrhosis. Over-expression of platelet-derived growth factor has been demonstrated in human hepatocellular carcinoma (HCC) tumors and cell lines. Imatinib, a potent inhibitor of BCR-ABL and c-kit, also inhibits the platelet-derived growth factor receptor tyrosine kinase. The trial was designed to assess the efficacy and safety of imatinib in patients with unresectable HCC.

METHODS:

Eligibility criteria consisted of HCC patient over the age of 18 with reasonable organ function, unresectable but measurable disease, not candidates for chemoinfusion, and a performance status of 0 to 2. Imatinib was started at 300 mg/d orally with 100 mg/wk dose escalation up to 800 mg/d if toxicity permitted.

RESULTS:

Fifteen patients, median age 58 years, were enrolled and treated with imatinib. Most, or 7, patients had hepatitis B virus as a risk factor for HCC, followed by hepatitis C virus in 3 patients. Metastatic disease (American Joint Committee on Cancer stage IV) was noted in 13 patients and locally advanced (stage III) in the remainder. The median dose-level of imatinib was 500 mg/d. Two patients had stable disease lasting more than 2 months. The remainder progressed within 2 months of initiation of imatinib. No grade 3 or 4 hematologic toxicity was observed. Two patients had grade 3 elevated liver function tests during treatment; otherwise, there was no other grade 3 or 4 nonhematologic toxicity noted.

CONCLUSION:

Although toxicities were tolerable, imatinib as a monotherapy for the treatment of unresectable HCC has little, if any, significant efficacy.

PMID:
18376233
[PubMed - indexed for MEDLINE]
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