Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related Kaposi sarcoma.
Using a novel blinded intrapatient vehicle control design, we conducted a phase II study of topically administered halofuginone, an angiogenesis inhibitor that inhibits collagen type-I and matrix metalloproteinases (MMPs), in patients with AIDS-related Kaposi sarcoma. Serial Kaposi sarcoma biopsies assessed treatment effects on angiogenic factors and Kaposi sarcoma herpesvirus-latency associated nuclear antigen-1 (KSHV-LANA). We observed marked heterogeneity of KSHV-LANA expression. Although the small number of subjects whose response could be evaluated precluded definitive assessment of halofuginone's efficacy, we observed a significant decrease in type-I collagen only in halofuginone-treated lesions, but no effect on MMP-2. The trial design is applicable to future studies of topical agents.
Ireland Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Henry B
HB
Koon
Barbara
B
Fingleton
Jeannette Y
JY
Lee
Julia T
JT
Geyer
Ethel
E
Cesarman
Robert A
RA
Parise
Merrill J
MJ
Egorin
Bruce J
BJ
Dezube
David
D
Aboulafia
Susan E
SE
Krown
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000287:Administration, Topical; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D052999:Quinazolinones / Q000008:administration & dosage / Q000627:therapeutic use*; D012514:Sarcoma, Kaposi / Q000188:drug therapy*; D016037:Single-Blind Method; D055815:Young Adult
D000970:Antineoplastic Agents; D010880:Piperidines; D052999:Quinazolinones; C010176:halofuginone