Preliminary Observations on the Effect of Recombinant Leukocyte a Interferon in Homosexual Men with Kaposi's Sarcoma

Krown, Susan E.; Real, Francisco X.; Cunningham‐Rundles, Susanna; Myskowski, Patricia L.; Koziner, Benjamín; Fein, Seymour; Mittelman, Abraham; Oettgen, Herbert F.; Safai, Bijan

doi:10.1056/nejm198305053081806

Cited by 337 publications

(61 citation statements)

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“…So it was entirely by chance that these initial KS patients were treated at a time when study subjects were being given IFN at doses near the maximum tolerated dose. Of the first 12 such patients whose response to treatment could be evaluated, 5 (42%) showed complete or partial (≥50 %<100%) KS regression and 3 others showed minor responses [7]. At the time, relatively little was known about the mechanisms of IFNα's action against cancer, and even less about the nature or cause of KS.…”

Section: Ifnα As Single Agent Therapy -A Requirement For High Ifn Dosesmentioning

confidence: 99%

“…Recombinant interferon alfa preparations (IFNα2a and IFNα2b), which had received approval from the U.S. Food and Drug Administration (FDA) for treatment of AIDS-associated KS in 1988, were still the only approved drugs for systemic treatment of KS (the chemotherapeutic agent, liposomal doxorubicin, would receive FDA approval later in 1995, as did liposomal daunorubicin in 1996 and paclitaxel in 1997). Now, more than a quarter century after the first published reports describing AIDS and its association with KS [3-6] and our first modestly successful attempts to treat KS with IFNα [7], this agent is used infrequently to treat KS, although it still finds use in HIV-infected individuals co-infected with hepatitis C. In this brief review, I will summarize some of the history of IFNα in the treatment of AIDS-associated KS, concentrating on examples of clinical trials in which I have personally been involved, and consider whether there remains a potentially valuable role for this agent in KS treatment. …”

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AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

Krown

2007

Cytokine & Growth Factor Reviews

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Interferon alfa (IFNA) was one of the first agents to be used therapeutically in AIDS-associated Kaposi's sarcoma (KS) more than 25 years ago, and induces tumor regression in a subset of patients. Although much has been learned about the clinical role of IFNα in KS treatment, little is currently known about the mechanism(s) by which IFNA causes KS regression. This is despite a growing understanding of both KS pathogenesis and relevant IFNA activities. To a large extent other agents have supplanted IFNA as treatments for KS, but there may still remain a therapeutic role for IFNA, possibly in combination with other agents targeting angiogenesis and/or HHV-8-encoded human gene homologs that encode proteins involved in cell cycle regulation and signaling. KeywordsInterferon; Kaposi's sarcoma In 1995, when I was honored as a recipient of the ISICR Milstein Award, the AIDS epidemic had recently begun its 15 th year and the human immunodeficiency virus (HIV-1) had been isolated some 12 years previously [1]. However, the virus associated with Kaposi's sarcoma (KS), the most common AIDS-associated malignancy, had been described less than a year earlier [2], its significance was still in some question and its role in KS development had not been characterized, and the active combination drug regimens with which we now treat HIV infection had not yet become widely available. Recombinant interferon alfa preparations (IFNα2a and IFNα2b), which had received approval from the U.S. Food and Drug Administration (FDA) for treatment of AIDS-associated KS in 1988, were still the only approved drugs for systemic treatment of KS (the chemotherapeutic agent, liposomal doxorubicin, would receive FDA approval later in 1995, as did liposomal daunorubicin in 1996 and paclitaxel in 1997). Now, more than a quarter century after the first published reports describing AIDS and its association with KS [3-6] and our first modestly successful attempts to treat KS with IFNα [7], this agent is used infrequently to treat KS, although it still finds use in HIV-infected individuals co-infected with hepatitis C. In this brief review, I will summarize some of the history of IFNα in the treatment of AIDS-associated KS, concentrating on examples of clinical trials in which I have personally been involved, and consider whether there remains a potentially valuable role for this agent in KS treatment.

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Section: Ifnα As Single Agent Therapy -A Requirement For High Ifn Dosesmentioning

confidence: 99%

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confidence: 99%

AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

Krown

2007

Cytokine & Growth Factor Reviews

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“…2,6 KS is not curable, and while some cases of acquired immunodeficiency syndrome (AIDS)-related KS respond to highly active antiretroviral therapy (HAART) or interferon alpha, long-term palliative cytotoxic therapy is often required. [7][8][9][10][11] However, cumulative toxicity can limit the ability to continue otherwise effective therapy. The development of less toxic patient self-administered long-term therapy would thus be an important therapeutic advance.…”

Section: Introductionmentioning

confidence: 99%

Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma

Little

Pluda

Wyvill

et al. 2006

Blood

106

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Interleukin-12 (IL-12) enhances Th1-type T-cell responses and exerts antiangiogenic effects. We initiated a phase 1 pilot study of IL-12 in 32 patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) whose KS was progressing while on antiretroviral therapy. Fifteen patients had poor prognosis T 1 S 1 disease. IL-12 was administered subcutaneously twice weekly at doses from 100 to 625 ng/kg. The maximum tolerated dose was 500 ng/kg, and the principal toxicities were flulike symptoms, transaminase or bilirubin elevations, neutropenia, hemolytic anemia, and depression. No tumor responses were seen at the lowest dose (100 ng/kg), but 17 of 24 evaluable patients at the higher doses had partial or complete responses (response rate, 71%; 95% confidence interval, 48%-89%). Only 3 of 17 patients had a change in antiretroviral therapy before responding, and there were no significant differences between responders and nonresponders with regard to changes in CD4 counts or viral loads.Patients had increases in their serum IL-12, interferon-␥, and inducible protein-10 (IP-10) after the first dose, and increases above baseline persisted after week 4. These results provide preliminary evidence that IL-12 has substantial activity against AIDS-related KS with acceptable toxicity and warrants further investigation for this indication. (Blood. 2006; 107:4650-4657)

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“…In particular, pulmonary KShas a poor prognosis because of the absence of effective treatment. Anumberof drugs have been found to have activity in the treatment of KS, including doxorubicin, bleomycin, vincristine, and liposomal anthracyclines (2)(3)(4). Although liposomal antracyclines are reported to be the treatment of choice for advanced AIDS-associated KS at present, combination chemotherapy composed of doxorubicin, bleomycin, and vincristine (ABV) is still the first-line therapy in Japan because of the difficulty of drug availability.…”

Section: Introductionmentioning

confidence: 99%

Successful Treatment with Paclitaxel of Advanced AIDS-associated Kaposi's Sarcoma.

et al. 2002

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Kaposi's sarcoma (KS) is the most prevalent AIDS-associated tumor. Wereport a 44-year-old Japanese manwith advanced AIDS-associated KS, which was spread over bilateral pulmonary parenchyma. He was initially treated with combination chemotherapy with a partial response.Uponthe recurrence of his KStwo months after the completion of the combination chemotherapy, the patient received paclitaxel, which brought about a complete response. Highly active antiretrovial therapy (HAART) was initiated three months before the combination chemotherapy, and the CD4+T-cell count had risen before starting paclitaxel. His clinical course suggests that paclitaxel was highly effective for KS disease control as previously reported, and that immunerestoration with HAART is crucial in the treatment of KS.

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Preliminary Observations on the Effect of Recombinant Leukocyte a Interferon in Homosexual Men with Kaposi's Sarcoma

Cited by 337 publications

References 20 publications

AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma

Successful Treatment with Paclitaxel of Advanced AIDS-associated Kaposi's Sarcoma.

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