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Kaposi’s sarcoma in children: An open randomised trial of vincristine, oral etoposide and a combination of vincristine and bleomycin

Published:March 17, 2014DOI:https://doi.org/10.1016/j.ejca.2014.02.019

      Abstract

      Introduction

      Kaposi’s sarcoma (KS) is a common childhood cancer in places where HIV is endemic and access to antiretroviral therapy (ART) is delayed. Despite this there are no randomised trials to compare and assess chemotherapeutic regimens.

      Method

      An open label, randomised trial comparing intravenous vincristine alone, vincristine and bleomycin and oral etoposide, was carried out in children with Kaposi’s sarcoma in the Queen Elizabeth Central Hospital, Blantyre, Malawi. HIV infected children were given ART after 2–3 courses of chemotherapy if they were not already on treatment. Neither HIV nor widespread KS are curable and treatment is aimed at disease reduction and improved quality of life. Tumour reduction was assessed by measuring the size of sentinel KS nodules and quality of life (QoL) by using the Lansky score. Follow up was until death or for one year.

      Findings

      92 children were enrolled of whom 46% were naïve to ART; 10 (11%) were HIV negative. Survival was not influenced by age or gender but was better in the oral etoposide and the vincristine and bleomycin groups. P = 0.0045. The group receiving oral etoposide had a better quality of life. Toxicity was not significant, and any drop in haemoglobin or white cell count could have been causally related to HIV infection rather than cytotoxic therapy.

      Conclusion

      Oral etoposide is a safe, effective treatment to contain KS and improve QoL which can be achieved without many visits to the hospital and intravenous injections.

      Keywords

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      References

        • Molyneux E.M.
        Childhood malignancies in Malawi 1967–76.
        East Afr Med J. 1979; 56: 15-21
        • Friedman-Kien A.E.
        • Laubenstein L.J.
        • Rubinstein P.
        • Buimovici-Klein E.
        • Marmor M.
        • Stahl R.
        • et al.
        Disseminated Kaposi sarcoma in homosexual men.
        Ann Intern Med. 1982; 96: 693-700
        • Bayley A.C.
        Occurrence, clinical behaviour and management of Kaposi sarcoma in Zambia.
        Cancer Surv. 1991; 10: 53-71
        • Sinfield R.L.
        • Molyneux E.M.
        • Banda K.
        • Borgstein E.
        • Broadhead R.
        • Hesseling P.
        • et al.
        Spectrum and presentation of pediatric malignancies in the HIV era experience from Blantyre, Malawi, 1998–2003.
        Pediatr Blood Cancer. 2007; 48: 515-520
        • Orem J.
        • Otieno M.W.
        • Remick S.C.
        AIDS-associated cancer in developing nations.
        Curr Opin Oncol. 2004; 16: 468-476
        • Davidson A.
        • Hendricks M.
        • Geel J.
        • et al.
        Malignancy in HIV positive South African children.
        Pediatr Blood Cancer. 2009; 53: 719
        • Msyamboza K.P.
        • Dzamalala C.
        • Mdokwe C.
        • Kamiza S.
        • Lemerani M.
        • Dzowela T.
        • et al.
        Burden of cancer in Malawi; common types, incidence and trends: national population-based cancer registry.
        BMC Res Notes. 2012; 16: 149https://doi.org/10.1186/1756-0500-5-149
        • Gantt S.
        • Carlsson J.
        • Ikoma M.
        • Gachelet E.
        • Gray M.
        • Geballe A.P.
        • et al.
        The HIV protease inhibitor nelfinavir inhibits Kaposi’s sarcoma-associated herpesvirus replication in vitro.
        Antimicrob Agents Chemother. 2011; 55: 2696-2703
        • Krown S.E.
        • Testa M.A.
        • Huang J.
        AIDS-related Kaposi’s sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee.
        J Clin Oncol. 1997; 15: 3085-3092
        • Nasti G.
        • Talamini R.
        • Antinori A.
        • et al.
        AIDS-related Kaposi’s sarcoma: evaluation of potential new prognostic factors and assessment of the AIDS Clinical Trial Group Staging System in the Haart Era—the Italian Cooperative Group on AIDS and Tumors and the Italian cohort of patients naive from antiretrovirals.
        J Clin Oncol. 2003; 21: 2876-2882
        • Molyneux E.M.
        • Davidson A.
        • Orem J.
        • Hesseling P.
        • Kambugu J.
        • Githanga J.
        • et al.
        The management of children with Kaposi’s sarcoma in resource limted settings.
        Pediatric Blood Cancer. 2013; 60: 538-542
        • Lorenzo G.D.
        • Konstantinopoulos P.A.
        • et al.
        Management of AIDS-related Kaposi’s sarcoma.
        Lancet Oncol. 2007; 82: 167
        • Saville M.W.
        • Liettzau J.
        • Pluda J.M.
        • et al.
        Treatment of HIV associated Kaposi’s sarcoma with Paclitaxel.
        Lancet. 1995; 346: 26-28
        • Gill P.S.
        • Tupule A.
        • Espina B.M.
        • et al.
        Paclitaxel is safe and effective in treatment of advanced AIDS-related Kaposi’s sarcoma.
        J Clin Oncol. 1999; 17: 1576-1883
        • Welles L.
        • Saville M.W.
        • Lietzau J.
        • et al.
        Phase II trial with dose titration of paclitaxel for therapy of HIV associated Kaposi’s sarcoma.
        J Clin Oncol. 1998; 16: 1112-1121
        • Tazio E.
        • Machado E.W.
        • Santana R.de C.
        • Fonseca B.A.L.
        • Schwartsman G.
        Systemic treatment of AIDS-related Kaposi’s sarcoma: current status and prospective.
        Cancer Treat Rev. 2006; 32: 445-455
        • Hande K.R.
        Etoposide: four decades of development of topoisomerase II inhibitor.
        Eur J Cancer. 1998; 34: 1514-1521
        • Mlombe Y.
        Management of HIV-associated Kaposi sarcoma in Malawi.
        Malawi Med J. 2008; 20: 129-132
        • Olweny C.L.M.
        • Borok M.
        • Guddza I.
        • et al.
        Treatment of AIDS-associated Kaposi’s sarcoma in Zimbabwe: results of a randomized quality of life clinical trial.
        Int J Cancer. 2005; 13: 632-639
        • Theron S.
        • Andronikou S.
        • George R.
        • et al.
        Non-infective pulmonary disease in HIV-positive children.
        Pediatr Radiol. 2009; 39: 555-564
      1. National Cancer Institute. Common toxicity criteria V3.0; 2003. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHSMarch 31, 2003 <http://ctep.cancer.gov> (Publish Date: August 9, 2006) [accessed 15.10.13].

        • Krown S.E.
        • Testa M.A.
        • Huang J.
        AIDS-related Kaposi sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee.
        J Clin Oncol. 1997; 15: 3085-3092
        • Gill P.S.
        • Rarick M.
        • McCutchan J.A.
        • Slater L.
        • Parker B.
        • Muchmore E.
        • et al.
        Systemic treatment of AIDS-related Kaposi sarcoma: results of a randomized trial.
        Am J Med. 1991; 90: 427-433
        • Hernandez D.E.
        • Perez J.R.
        Advanced epidemic Kaposi sarcoma: treatment with bleomycin or combination of doxorubicin, bleomycin, and vincristine.
        Int J Dermatol. 1996; 35: 831-833
        • Nasti G.
        • Errante D.
        • Santarossa S.
        • Vaccher E.
        • Tirelli U.
        A risk and benefit assessment of treatment for AIDS-related Kaposi sarcoma.
        Drug Saf. 1999; 20: 403-425
        • Anglemyer A.
        • Agrawal A.
        • Rutherford G.
        Treatment of Kaposi’s sarcoma in children with HIV-1 infection. . 2014, 1, CD009826.
        Cochrane Database Syst Rev. 2014; 1: CD009826https://doi.org/10.1002/14651858.CD009826.pub2
        • Murdoch D.M.
        • Venter W.D.
        • Feldman C.
        • Van R.A.
        Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective study.
        AIDS. 2008; 22: 601-610
        • Letang E.
        • Almeida J.M.
        • Miro J.M.
        • Ayala E.
        • White I.E.
        • Carrilho C.
        • et al.
        Predictors of immune reconstitution inflammatory syndrome-associated with Kaposi sarcoma in Mozambique: a prospective study.
        J Acquir Immune Defic Syndr. 2010; 53: 589-597
        • Gantt S.
        • Kakuru A.
        • Wald A.
        • et al.
        Clinical presentation and outcome of epidemic Kaposi sarcoma in Ugandan children.
        Pediatr Blood Cancer. 2010; 54: 670-674
        • Sinfield R.
        • Molyneux E.M.
        • Banda K.
        • Broadhead R.L.
        • Borgstein E.
        • Mkandawire N.K.
        • et al.
        The prevalence, presentation of paediatric malignancies in Blantyre Malawi in the HIV era, 1998–2003.
        Pediatr Blood Cancer. 2007; 48: 515-520
        • Balagadde-Kambugu J.
        • Orem J.
        • Stefan D.C.
        HIV and malignancy in children in pediatric hematology–oncology in countries with limited resources.
        in: Stefan D.C. Rodriguez-Galindo C. A practical manual. Springer, New York, Heidelberg, Dordrecht, London2013
        • Vaz P.
        • Macassa E.
        • Jani I.
        • Thome B.
        • Mahagaja E.
        • Madede T.
        • et al.
        Treatment of Kaposi sarcoma in human immunodeficiency virus-1 infected Mozambican children with antiretroviral drugs and chemotherapy.
        Pediatr Infect Dis J. 2011; 30: 891
        • Evans S.R.
        • Krown S.E.
        • Testa M.A.
        • Cooley T.P.
        • Von Roenn J.H.
        Phase II evaluation of low dose oral etoposide for the treatment of relapsed or progressive AIDS-related Kaposi’s sarcoma: an AIDS Clinical Trials Group Clinical Study.
        J Clin Oncol. 2002; 20: 3236-3241
        • Cox C.
        • El-Mallawany N.
        • Kabue M.
        • et al.
        Clinical characteristics and outcomes of HIV-infected children diagnosed with Kaposi sarcoma in Malawi and Botswana.
        Pediatr Blood Cancer. 2013; 60: 1274-1280
        • Stefan D.C.
        • Stones D.K.
        • Wainwright L.
        • et al.
        Kaposi sarcoma in South African Children.
        Pediatr Blood Cancer. 2011; 56: 392-396