title: Interferon-alpha2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma: an AIDS malignancy consortium phase I trial.
abstract: We evaluated the safety and maximum tolerated dose of interferon (IFN)-alpha2b 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/muL at baseline to a maximum on-study value of 359 cells/muL. 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.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. krowns@mskcc.org
authors.forename: Susan E
authors.initials: SE
authors.lastname: Krown
authors.forename: Jeannette Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Fischl
authors.forename: Richard
authors.initials: R
authors.lastname: Ambinder
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Von Roenn
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005221:Fatigue / Q000209:etiology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D019288:Herpesvirus 8, Human; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D011994:Recombinant Proteins; D012074:Remission Induction; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins