TY - JOUR
T1 - A phase 1b/pharmacokinetic trial of PTC299, a novel posttranscriptional VEGF inhibitor, for AIDS-related Kaposi's Sarcoma
T2 - AIDS malignancy consortium trial 059
AU - for the AIDS Malignancy Consortium (AMC)-059 Study Team
AU - Ignacio, Rachel A.Bender
AU - Lee, Jeannette Y.
AU - Rudek, Michelle A.
AU - Dittmer, Dirk P.
AU - Ambinder, Richard F.
AU - Krown, Susan E.
AU - Aboulafia, David
AU - Baiocchi, Robert
AU - Chiao, Elizabeth Y.
AU - Dezube, Bruce J.
AU - Mitsuyasu, Ronald T.
AU - Reid, Erin Gourley
AU - Shiramizu, Bruce
AU - Sparano, Joseph A.
AU - Tulpule, Anil
AU - Eason, Anthony
AU - Chavakula, Veenadhari
AU - Lynne, Julia
N1 - Publisher Copyright:
© Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Vascular endothelial growth factor (VEGF) plays an important role in Kaposi's sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received 3 different doses of PTC299. Adverse events typically observed with VEGF inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KS-associated herpesvirus DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KS-associated herpesvirus proliferation.
AB - Vascular endothelial growth factor (VEGF) plays an important role in Kaposi's sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received 3 different doses of PTC299. Adverse events typically observed with VEGF inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KS-associated herpesvirus DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KS-associated herpesvirus proliferation.
KW - HIV/AIDS-related malignancy
KW - Kaposi's sarcoma (KS)
KW - Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)
KW - Pharmacokinetics (PK)
KW - Vascular endothelial growth factor (VEGF)
KW - Vascular endothelial growth factor inhibitor (VEGF inhibitor)
UR - http://www.scopus.com/inward/record.url?scp=84951304513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951304513&partnerID=8YFLogxK
U2 - 10.1097/QAI.0000000000000918
DO - 10.1097/QAI.0000000000000918
M3 - Article
C2 - 26689971
AN - SCOPUS:84951304513
SN - 1525-4135
VL - 72
SP - 52
EP - 57
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 1
ER -