Safety and efficacy of pegylated liposomal doxorubicin in HIV-associated Kaposi's sarcoma

Francesca Cainelli, Alfredo Vallone, Francesca Cainelli, Alfredo Vallone

Abstract

Kaposi's sarcoma is a vascular tumor linked to the presence of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) and the incidence of which has increased considerably the world over after the onset of the human immunodeficiency virus (HIV) pandemic. Antiretroviral therapy combined with cytotoxic agents has been established as the treatment of choice in the past 10 years. Among chemotherapeutic agents, pegylated liposomal doxorubicin has become the preferred one for patients with HIV-associated Kaposi's sarcoma in Western countries. The drug in this formulation localizes better to the tumor and has higher efficacy. Skin toxicity, mucositis, and leukopenia/neutropenia are the main side effects. Hepatotoxicity and mild cardiotoxicity are observed less frequently. Pegylated liposomal doxorubicin impacts favorably on quality of life. Although cost effective in Western countries, the drug is less so in developing countries.

Keywords: HIV infection; Kaposi’s sarcoma; pegylated liposomal doxorubicin.

References

    1. Engels EA, Biggar RJ, Marshall VA, et al. Detection and quantitation of Kaposi’s sarcoma associated herpes virus to predict AIDS associated Kaposi’s sarcoma. AIDS. 2003;17:1847–1851.
    1. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266:1865–1869.
    1. Moore PS, Gao SJ, Dominguez G, et al. Primary characterization of a herpesvirus agent associated with Kaposi’s sarcoma. J Virol. 1996;70:549–558.
    1. Cesarman E, Chang Y, Moore PS, et al. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995;332:1186–1191.
    1. Soulier J, Grollet L, Oskenhendler E, et al. Kaposi’s sarcoma–associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood. 1995;86:1276–1280.
    1. Biggar RJ, Chaturvedi AK, Goedert JJ, Engels EA HIV/AIDS Cancer Match Study. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst. 2007;99(12):962–972.
    1. Goedert JJ. The epidemiology of acquired immunodeficiency syndrome malignancies. Semin Oncol. 2000;27:390–401.
    1. Cook-Mozaffari P, Newton R, Beral V, et al. The geographical distribution of Kaposi’s sarcoma and of lymphomas in Africa before the AIDS epidemic. Br J Cancer. 1998;78:1521–1528.
    1. Sitas F, Newton R. Kaposi’s sarcoma in South Africa. J Natl Cancer Inst Monog. 2001;28:1–4.
    1. Cheung MC, Pantanowitz L, Dezube BJ. AIDS-related malignancies: emerging challenges in the era of highly active antiretroviral therapy. Oncologist. 2005;10(6):412–426.
    1. Ioachim HL, Adsay V, Giancotti FR, et al. Kaposi’s sarcoma of internal organs. A multiparameter study of 86 cases. Cancer. 1995;75:1376–1385.
    1. Dezube BJ, Pantanowitz L, Aboulafia DM. Management of AIDS-related Kaposi sarcoma: advances in target discovery and treatment. AIDS Read. 2004;14:236–238. 243–244, 251–253.
    1. Schiff NF, Annino DJ, Woo P, et al. Kaposi’s sarcoma of the larynx. Ann Otol Rhinol Laryngol. 1997;106:563–567.
    1. Huang L, Schnapp LM, Gruden JF, et al. Presentation of AIDS-related pulmonary Kaposi’s sarcoma diagnosed by bronchoscopy. Am J Respir Crit Care Med. 1996;153:1385–1390.
    1. Dezube BJ. Acquired immunodeficiency syndrome related Kaposi’s sarcoma: clinical features, staging, and treatment. Semin Oncol. 2000;27:424–430.
    1. Real FX, Krown SE. Spontaneous regression of Kaposi’s sarcoma in patients with AIDS. N Engl J Med. 1985;313:1659.
    1. Coukell A, Spencer CM. Polyethylene glycol-liposomal doxorubicin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the management of AIDS-related Kaposi’s sarcoma. Drugs. 1997;53(3):520–538.
    1. Haran G, Cohen R, Bar LK, et al. Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Biochim Biophys Acta. 1990;1025:143–151.
    1. Lasic DD, Frederk PM, Stuart MCA, et al. Gelation of liposome interior. A novel method for drug encapsulation. FEBS Lett. 1992;312:255–258.
    1. Papahadjopoulos D, Allen T, Gabizon A, et al. Sterically stabilized liposomes: improvements in pharmacokinetics and anti-tumor therapeutic efficacy. Proc Natl Acad Sci U S A. 1991;88:11460–11464.
    1. Balmer C, Valley AW. Basic principles of cancer treatment and cancer chemotherapy. In: Di Piro JT, Talbert RL, Hayes PE, et al., editors. Pharmacotherapy: A pathophysiologic approach. 2nd ed. Norwalk, CT: Appleton and Lange; 1993. pp. 1879–1929.
    1. Meriwether WD, Bachur NR. Inhibition of DNA and RNA metabolism by daunorubicin and adriamycin in L1210 mouse leukemia. Cancer Res. 1972;32(6):1137–1142.
    1. Hortobágyi GN. Anthracyclines in the treatment of cancer. Drugs. 1997;54(Suppl 4):1–7.
    1. Speyer J, Wasserheit C. Strategies for reduction of anthracycline cardiac toxicity. Semin Oncol. 1998;25(5):525–537.
    1. Stürzl M, Zietz C, Eisenburg B, et al. Liposomal doxorubicin in the treatment of AIDS-associated Kaposi’s sarcoma: clinical, histological and cell biological evaluation. Res Virol. 1994;145(3–4):261–269.
    1. Sharpe M, Easthope SE, Keating GM, Lamb HM. Polyethylene glycol-liposomal doxorubicin: a review of its use in the management of solid and haematological malignancies and AIDS-related Kaposi’s sarcoma. Drugs. 2002;62(14):2089–2126.
    1. Simpson JK, Miller RF, Spittle MF. Liposomal doxorubicin for treatment of AIDS-related Kaposi’s sarcoma. Clin Oncol. 1993;5:372–374.
    1. Harrison M, Tomlinson D, Stewart S. Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1995;13:914–920.
    1. Northfelt DW, Dezube BJ, Thommes JA, et al. Pegylated liposomal doxorubicin versus doxorubicin, bleomycin and vincristine in the treatment of AIDS-related Kaposi’s sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998;16:2445–2451.
    1. Stewart S, Jablonowski H, Goebel FD, et al. Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1998;16:683–691.
    1. Northfelt DW, Dezube BJ, Thommes JA, et al. Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS-related Kaposi’s sarcoma after failure of standard chemotherapy. J Clin Oncol. 1997;15:653–659.
    1. Martin-Carbonero L, Barrios A, Saballs P, et al. Pegylated liposomal doxorubicin plus highly active antiretroviral therapy versus highly active antiretroviral therapy alone in HIV patients with Kaposi’s sarcoma. AIDS. 2004;18(12):1737–1740.
    1. Lichterfeld M, Qurishi N, Hoffmann C, et al. Treatment of HIV-1-associated Kaposi’s sarcoma with pegylated liposomal doxorubicin and HAART simultaneously induces effective tumor remission and CD4+ T cell recovery. Infection. 2005;33:140–147.
    1. Goebel FD, Goldstein D, Goos M, Jablonowski H, Stewart JS. Efficacy and safety of stealth liposomal doxorubicin in AIDS-related Kaposi’s sarcoma. The International SL-DOX Study Group. Br J Cancer. 1996;73:989–994.
    1. Hengge UR, Esser S, Rudel HP, Goos M. Long-term chemotherapy of HIV-associated Kaposi’s sarcoma with liposomal doxorubicin. Eur J Cancer. 2001;37:878–883.
    1. Cooley T, Henry D, Tonda M, Sun S, O’Connell M, Rackoff W. A randomized, double-blind study of pegylated liposomal doxorubicin for the treatment of AIDS-related Kaposi’s sarcoma. Oncologist. 2007;12:114–123.
    1. Little RF, Aleman K, Kumar P, et al. Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. Blood. 2007;110:4165–4171.
    1. Martin-Carbonero L, Palacios R, Valencia E, et al. the Caelyx/KS Spanish study group. Long-term prognosis of HIV-infected patients with Kaposi’s sarcoma treated with pegylated liposomal doxorubicin. Clin Infect Dis. 2008;47:410–417.
    1. Nunez M, Saballs P, Valencia ME, et al. for the Caelyx/KS Spanish Study Group. Response to liposomal doxorubicin and clinical outcome of HIV-1–infected patients with Kaposi’s sarcoma receiving highly active antiretroviral therapy. HIV Clin Trials. 2001;2:429–437.
    1. Billingham M, Bristow M. Evaluation of anthracycline cardiotoxicity Predictive ability and functional correlation of endomyocardial biopsy. Cancer Treat Symp. 1984;3:71–76.
    1. Berry G, Billingham M, Alderman E, et al. The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi’s sarcoma patients treated with pegylated liposomal doxorubicin. Ann Oncol. 1998;9:711–716.
    1. Osoba D, Northfelt DW, Budd DW, et al. Effect of treatment on health-related quality of life in acquired immunodeficiency syndrome (AIDS)-related Kaposi’s sarcoma: a randomized trial of pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine. Cancer Invest. 2001;19(6):573–580.
    1. Bennett CL, Golub RM, Stinson TJ, et al. Cost-effectiveness analysis comparing liposomal anthracyclines in the treatment of AIDS-related Kaposi’s sarcoma. J Acquir Immune Defic Syndr. 1998;18(5):460–465.
    1. Hjortsberg C, Person U, Lidbrink E, et al. Cost-effectiveness analysis of pegylated-liposomal doxorubicin and liposomal daunorubicin treatments in patients with Kaposi’s sarcoma. Acta Oncol. 1999;38(8):1063–1067.
    1. Vanni T, Lopes Fonseca BA, Polanczyk CA. Cost-effectiveness analysis comparing chemotherapy regimens in the treatment of AIDS-related Kaposi’s sarcoma in Brazil. HIV Clin Trials. 2006;7(4):194–202.
    1. Iscovich J, Boffetta P, Brennan P. Classic Kaposi’s sarcoma as a first primary neoplasm. Int J Cancer. 1999;80:173–177.
    1. Bower M, Collins S, Cottrill C. British HIV Association guidelines for HIV-associated malignancies 2008. HIV Med. 2008;9:336–388.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera