TY - JOUR
T1 - Interferon-α2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma
T2 - An AIDS malignancy consortium phase I trial
AU - Krown, Susan E.
AU - Lee, Jeannette Y.
AU - Lin, Lan
AU - Fischl, Margaret A.
AU - Ambinder, Richard
AU - Von Roenn, Jamie H.
PY - 2006/2
Y1 - 2006/2
N2 - We evaluated the safety and maximum tolerated dose of interferon (IFN)-α2b in combination with protease inhibitor-based highly active antiretroviral therapy (HAART) in a phase 1 study in 14 patients with AIDS-associated Kaposi sarcoma (KS). Planned IFN dose levels were 0, 1, 5, 10, and 15 million IU administered by daily subcutaneous injection. Dose-limiting toxicities were neutropenia and malaise. The maximum tolerated IFN dose was 5 million IU/d. The median CD4 count increased from 260 cells/μL at baseline to a maximum on-study value of 359 cells/μL. In 6 patients with paired baseline and on-study values, the median HIV RNA level decreased from 20,179 copies/mL to a minimum on-study value of 309 copies/mL. Of 13 patients whose KS response could be evaluated, 5 showed objective tumor regression. Responses occurred in HAART-experienced and HAART-naive subjects. Five patients, including 2 responders, 2 with stable KS, and 1 with progression, had serial measurements of Kaposi sarcoma herpesvirus (KSHV) load. None of these patients, irrespective of treatment arm or KS response, showed durable clearance of KSHV from plasma or peripheral blood mononuclear cells. This study establishes a safe dose of IFN that can be used with HAART and, potentially, with other inhibitors of KS in future clinical trials.
AB - We evaluated the safety and maximum tolerated dose of interferon (IFN)-α2b in combination with protease inhibitor-based highly active antiretroviral therapy (HAART) in a phase 1 study in 14 patients with AIDS-associated Kaposi sarcoma (KS). Planned IFN dose levels were 0, 1, 5, 10, and 15 million IU administered by daily subcutaneous injection. Dose-limiting toxicities were neutropenia and malaise. The maximum tolerated IFN dose was 5 million IU/d. The median CD4 count increased from 260 cells/μL at baseline to a maximum on-study value of 359 cells/μL. In 6 patients with paired baseline and on-study values, the median HIV RNA level decreased from 20,179 copies/mL to a minimum on-study value of 309 copies/mL. Of 13 patients whose KS response could be evaluated, 5 showed objective tumor regression. Responses occurred in HAART-experienced and HAART-naive subjects. Five patients, including 2 responders, 2 with stable KS, and 1 with progression, had serial measurements of Kaposi sarcoma herpesvirus (KSHV) load. None of these patients, irrespective of treatment arm or KS response, showed durable clearance of KSHV from plasma or peripheral blood mononuclear cells. This study establishes a safe dose of IFN that can be used with HAART and, potentially, with other inhibitors of KS in future clinical trials.
KW - Highly active antiretroviral therapy
KW - Interferon-α
KW - Kaposi sarcoma
KW - Kaposi sarcoma herpesvirus
UR - http://www.scopus.com/inward/record.url?scp=33645287072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645287072&partnerID=8YFLogxK
U2 - 10.1097/01.qai.0000194237.15831.23
DO - 10.1097/01.qai.0000194237.15831.23
M3 - Article
C2 - 16394845
AN - SCOPUS:33645287072
SN - 1525-4135
VL - 41
SP - 149
EP - 153
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 2
ER -