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Oral Multikinase Inhibitors
There is presently one antiangiogenic agent called sorafenib (Nexavar) that is FDA-approved for the treatment of advanced liver cancer. Sorafenib belongs to a class of orally administered antiangiogenic drugs that are designed to pass through cancer cell membranes and target key pathways inside cells. In a phase 3 clinical trial called the SHARP trial, patients with liver cancer who received sorafenib lived almost 11 months on average, compared with about 8 months for those who received placebo.3

Sorafenib became the first medical treatment proven to prolong survival in advanced liver cancer. Although relatively few patients in the SHARP trial had visible shrinkage of their tumors, more than 70% had their tumors stop growing. Notably, tumors treated with antiangiogenic drugs often die from the inside outward as the blood supply is cut off. The outer tumor border may therefore appear to be the same size, even though much of the tumor center is dead.4 This observation may explain why patients treated with sorafenib in the SHARP study had prolonged survival without clear tumor shrinkage.

Sorafenib has also shown to be beneficial for liver cancer when combined with a chemotherapy agent called doxorubicin. In a phase 2 clinical study, the combination of sorafenib and doxorubicin significantly prolonged the time patients lived without their disease getting worse, a measure called progression-free survival (PFS).5 Overall survival time was also much greater (13.7 months versus 6.5 months) with the drug combination than with the chemotherapy by itself. Another antiangiogenic drug called sunitinib (Sutent®) showed early promise for liver cancer, but a later study was halted after patients on sunitinib were not surviving as long as those on sorafenib.6


Last updated May 29, 2011