Phase I and pharmacokinetic study of sorafenib in Kaposi sarcoma.

10588 Background: Kaposi sarcoma (KS) is a multifocal angioproliferative disorder. VEGFR2-3, PDGFR and c-kit are implicated in KS pathogenesis and inhibited by sorafenib (So). KS is commonly HIV-associated. The antiretroviral drug ritonavir (R) inhibits CYP3A4, and may affect So metabolism and tolerability. Methods: We performed a phase I study of So in KS. HIV+ patients (pts) were eligible if on combination antiretroviral therapy (cART) for >3 months with progressive KS or >4 months with no KS regression. Dose level 1 for pts on R-containing cART (R1) was So 200 mg daily, for pts not receiving R (NR1) So 200 mg every 12 hours. Treatment cycles were 21 days. So pharmacokinetic assessment performed cycle 1 day 8. Adverse event (AE) grade (Gr) by CTCAE v3.0 (2006-10) and v4.0 (2011-12). KS response graded by modified ACTG criteria. Results: 10 pts, R1 (8), NR1 (2). Baseline characteristics: median (med) (range) age 49 (35-72), CD4 in HIV+ 500 cells/uL (35, 747), time on cART 9 months (3.5, 27), previous KS ...