Advertisement

Drugs

, Volume 48, Issue 4, pp 569–582 | Cite as

Treatment of Kaposi’s Sarcoma

Current Guidelines and Future Perspectives
  • Donald W. Northfelt
Practical Therapeutics

Summary

Kaposi’s sarcoma is the most common malignancy associated with HIV infection, and the morbidity and mortality attributable to AIDS-related Kaposi’s sarcoma (AIDS-KS) may be increasing. No curative therapy is available for AIDS-KS, but palliative therapy can eliminate or reduce cosmetically unacceptable lesions, reduce painful or unsightly oedema or lymphadenopathy, shrink symptomatic oral lesions and relieve symptoms caused by visceral involvement.

Strategies currently employed to treat the various clinical problems encountered in AIDS-KS include single- and multi-agent cytotoxic chemotherapy, treatment with interferon-α, radiotherapy, and other local therapies. Current clinical research is focusing on use of liposome-encapsulated cytotoxic agents and treatment with substances that inhibit angiogenesis.

Any treatment plan for AIDS-KS must be flexible and must be based on the patient’s overall clinical and immunological status as well as therapeutic goals. Limited local disease is usually amenable to treatment with local measures. Extensive, symptomatic AIDS-KS warrants systemic treatment. The response of mucocutaneous lesions to low dose systemic cytotoxic chemotherapy is typically excellent. Treatment with interferon-α may also be beneficial in this setting. Multi-agent chemotherapeutic regimens are usually reserved for treatment of patients most severely affected by AIDS-KS. It is hoped that liposome-encapsulated cytotoxic chemotherapy and antiangiogenic therapies will prove more effective and less toxic than the treatment strategies currently in use.

Keywords

Doxorubicin Adis International Limited Bleomycin Vinblastine Visceral Involvement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Friedman-Kein A, Laubenstein L, Marmor M, et al. Kaposi’s sarcoma and pneumocystis pneumonia among homosexual men — New York City and California. MMWR 1981; 30: 305–8Google Scholar
  2. 2.
    Hymes KB, Cheung TL, Green JB, et al. Kaposi’s sarcoma in homosexual men: a report of eight cases. Lancet 1981; 2: 598–600PubMedCrossRefGoogle Scholar
  3. 3.
    Masur H, Michilis MA, Green JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestations of cellular immune dysfunction. N Engl J Med 1981; 305: 1431–8PubMedCrossRefGoogle Scholar
  4. 4.
    Beral V, Peterman TA, Berkelman RL, et al. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 1990; 1: 123–8CrossRefGoogle Scholar
  5. 5.
    Rutherford GW, Schwarcz SK, Lemp GF, et al. Epidemiology of AIDS-related Kaposi’s sarcoma in San Francisco. J Infect Dis 1989; 159: 569–71PubMedCrossRefGoogle Scholar
  6. 6.
    Cusick PS, Moss AR, Bacchetti P, et al. Serologie variables at diagnosis with Kaposi’s sarcoma (KS): predictors of shortened survival [abstract]. Vth International Conference on AIDS; 1989: Montreal; poster WCP 38: 598Google Scholar
  7. 7.
    Gill PS, Akil B, Colletti P, et al. Pulmonary Kaposi’s sarcoma: clinical findings and results of therapy. Am J Med 1989; 87: 57–61PubMedCrossRefGoogle Scholar
  8. 8.
    Kaplan LD, Hopewell PC, Jaffe H, et al. Kaposi’s sarcoma involving the lung in patients with acquired immunodeficiency syndrome. J Acquired Imm Def Synd 1988; 1: 23–30Google Scholar
  9. 9.
    Centers for Disease Control. Epidemiologie aspects of the current outbreak of Kaposi’s sarcoma and opportunistic infections. N Engl J Med 1982; 306: 248–52Google Scholar
  10. 10.
    Kaposi M. Idiopathisches multiples Pigmentsarkom der Haut. Arch Dermatol Syph 1872; 4: 265–73Google Scholar
  11. 11.
    Taylor JF, Templeton AC, Vogel CL, et al. Kaposi’s sarcoma in Uganda: a clinico-pathological study. Int J Cancer 1971; 3: 122–35CrossRefGoogle Scholar
  12. 12.
    Harwood AR, Osoba D, Hofstader SL, et al. Kaposi’s sarcoma in recipients of renal transplants. Am J Med 1979; 67: 759–65PubMedCrossRefGoogle Scholar
  13. 13.
    Penn I. Tumors of the immunocompromised patient. Ann Rev Med 1988; 39: 6373CrossRefGoogle Scholar
  14. 14.
    Mitsuyasu R, Groopman JE. Biology and therapy of Kaposi’s sarcoma. Semin Oncol 1984; 11: 53–9PubMedGoogle Scholar
  15. 15.
    Safai B. Pathophysiology and epidemiology of epidemic Kaposi’s sarcoma. Semin Oncol 1987; 2 Suppl. 3: 7–12Google Scholar
  16. 16.
    Peters BS, Beck EJ, Coleman DG, et al. Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS. Br J Med 1991; 302: 203–7CrossRefGoogle Scholar
  17. 17.
    Lemp GF, Payne SF, Neal D, et al. Survival trends for patients with AIDS. JAMA 1990; 263: 402–6PubMedCrossRefGoogle Scholar
  18. 18.
    Volberding PA, Abrams DI, Conant M, et al. Vinblastine therapy for Kaposi’s sarcoma in the acquired immunodeficiency syndrome. Ann Intern Med 1985; 103: 335–8PubMedGoogle Scholar
  19. 19.
    Mintzer DM, Real FX, Jovino L, et al. Treatment of Kaposi’s sarcoma and thrombocytopenia with vincristine in patients with acquired immunodeficiency syndrome. Ann Intern Med 1985; 102: 200–2PubMedGoogle Scholar
  20. 20.
    Laubenstein LJ, Krigel RL, Odajnyk CM, et al. Treatment of epidemic Kaposi’s sarcoma with etoposide or a combination of doxorubicin, bleomycin and vinblastine. J Clin Oncol 1984; 2: 1115–20PubMedGoogle Scholar
  21. 21.
    Caumes E, Guermonprez G, Katlama C, et al. AIDS-associated mucocutaneous Kaposi’s sarcoma treated with bleomycin. AIDS 1992; 6: 1483–7PubMedCrossRefGoogle Scholar
  22. 22.
    Lassoued K, Clauvel J-P, Katlama C, et al. Treatment of the acquired immune deficiency syndrome-related Kaposi’s sarcoma with bleomycin as a single agent. Cancer 1990; 66: 1869–72PubMedCrossRefGoogle Scholar
  23. 23.
    Remick SC, Reddy M, Herman D, et al. Continuous infusion bleomycin in AIDS-related Kaposi’s sarcoma. J Clin Oncol 1994; 12(6): 1130–6PubMedGoogle Scholar
  24. 24.
    Fertakos RJ, Mintzer DM. Digital gangrene following chemotherapy for AIDS-related Kaposi’s sarcoma. Am J Med 1992; 93: 581–2PubMedCrossRefGoogle Scholar
  25. 25.
    von Gunten CF, Roth EL, von Roenn JH. Raynaud phenomenon in three patients with acquired immune deficiency syndrome-related Kaposi’s sarcoma treated with bleomycin. Cancer 1993; 72: 2004–6CrossRefGoogle Scholar
  26. 26.
    Vayssairat M, Gaitz JP, Bamberger N. Digital gangrene, HIV infection and bleomycin treatment. J Rheumatol 1993; 20: 921PubMedGoogle Scholar
  27. 27.
    Fischl MA, Krown SE, O’Boyle KP, et al. Weekly doxorubicin in the treatment of patients with AIDS-related Kaposi’s sarcoma. J Acquir Immun Defic Synd 1993; 6: 259–64Google Scholar
  28. 28.
    Gill PS, Rarick M, McCutchan JA, et al. Systemic treatment of AIDS-related Kaposi’s sarcoma: results of a randomized trial. Am J Med 1991; 90: 427–33PubMedGoogle Scholar
  29. 29.
    Chachoua A, Green M, Laubenstein L, et al. Phase II study of oral idarubicin in patients with AIDS-associated Kaposi’s sarcoma. Cancer Treat Rep 1987; 71: 775–6PubMedGoogle Scholar
  30. 30.
    Kaplan L, Volberding PA. Failure (and danger) of mitoxantrone in AIDS-related Kaposi’s sarcoma. Lancet 1985; 2: 396PubMedCrossRefGoogle Scholar
  31. 31.
    Chachoua A, Green M, Wernz J, et al. Phase II trial of ICRF-187 in patients with acquired immune deficiency related Kaposi’s sarcoma (AIDS-KS). Invest New Drugs 1989; 7: 327–31PubMedCrossRefGoogle Scholar
  32. 32.
    Goss PE, Shepherd FA, Burkes R, et al. Phase II study of epirubicin in the treatment of Kaposi’s sarcoma and AIDS. Proc ASCO 1989;3: 2Google Scholar
  33. 33.
    Kaplan L, Abrams D, Volberding P. Treatment of Kaposi’s sarcoma in acquired immunodeficiency syndrome with an alternating vincristine-vinblastine regimen. Cancer Treat Rep 1986; 70: 1121–2PubMedGoogle Scholar
  34. 34.
    Gelmann EP, Longo D, Lane HC, et al. Combination chemotherapy of disseminated Kaposi’s sarcoma in patients with the acquired immune deficiency syndrome. Am J Med 1987; 82: 456–62PubMedCrossRefGoogle Scholar
  35. 35.
    Shields PG, Dawkins F, Holmlund J, et al. Low-dose multidrug chemotherapy plus Pneumocystis carinii pneumonia prophylaxis for HIV-related Kaposi’s sarcoma. J Acquir Immun Defic Synd 1990; 3: 695–700Google Scholar
  36. 36.
    Sloand E, Kumar PN, Pierce PF. Chemotherapy for patients with pulmonary Kaposi’s sarcoma: benefit of filgrastim (G-CSF) in supporting dose administration. South Med J 1993; 86: 1219–24PubMedCrossRefGoogle Scholar
  37. 37.
    Gill P, Rarick M, Bernstein-Singer M, et al. Treatment of advanced Kaposi’s sarcoma using a combination of bleomycin and vincristine. Am J Clin Oncol 1990; 13: 315–19PubMedCrossRefGoogle Scholar
  38. 38.
    Rarick MU, Gill PS, Montgomery T, et al. Treatment of epidemic Kaposi’s sarcoma with combination chemotherapy (vincristine and bleomycin) and zidovudine. Ann Oncol 1990; 1: 147–9.PubMedGoogle Scholar
  39. 39.
    Gompels MM, Hill A, Jenkins P, et al. Kaposi’s sarcoma in HIV infection treated with vincristine and bleomycin. AIDS 1992; 6: 1175–80PubMedCrossRefGoogle Scholar
  40. 40.
    Lipman MCI, Swaden LS, Sabin CA, et al. Kaposi’s sarcoma in HIV infection treated with vincristine and bleomycin. AIDS 1993; 7: 592–3PubMedCrossRefGoogle Scholar
  41. 41.
    Laine L, Amerian J, Rarick M, et al. The response of symptomatic gastrointestinal Kaposi’s sarcoma to chemotherapy: a prospective evaluation using an endoscopie method of disease quantification. Am J Gastroenterol 1990; 85: 959–61PubMedGoogle Scholar
  42. 42.
    Gill PS, Rarick MU, Espina B, et al. Advanced acquired immune deficiency syndrome-related Kaposi’s sarcoma: results of pilot studies using combination chemotherapy. Cancer 1990; 65: 1074–8PubMedCrossRefGoogle Scholar
  43. 43.
    Gill PS, Bernstein-Singer M, Espina BM, et al. Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte-macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi’s sarcoma. AIDS 1992; 6: 1477–81PubMedCrossRefGoogle Scholar
  44. 44.
    Francis ML, Meltzer MS, Gendelman HE. Interferons in the persistence, pathogenesis, and treatment of HIV infection. AIDS Res Human Retrovir 1992; 8: 199–207CrossRefGoogle Scholar
  45. 45.
    Dorr RT. Interferon-α in malignant and viral diseases. Drugs 1993; 45: 177–211PubMedCrossRefGoogle Scholar
  46. 46.
    Krown SE. Interferon and other biologic agents for the treatment of Kaposi’s sarcoma. Hematol Oncol Clin N Am 1991; 5: 311–22Google Scholar
  47. 47.
    Krown SE, Real FX, Lester T, et al. Interferon-a (IFN-α2a) ± vinblastine in AIDS-related Kaposi’s sarcoma: a prospective randomized trial. Proc ASCO 1986; 5: 6Google Scholar
  48. 48.
    Fischl MA, Gorowski E, Koch G, et al. Interferon alfa-nl (Wellferon®) in Kaposi’s sarcoma: single agent or combination with vinblastine. In: Cantell K, Schellekens H, editors. The Biology of the Interferon System 1986. Boston: Martinus Nijhoff, 1987: 355–62CrossRefGoogle Scholar
  49. 49.
    Krigel RL, Slywotzky CM, Lonberg M, et al. Treatment of epidemic Kaposi’s sarcoma with a combination of interferon alpha 2b and etoposide. J Biol Response Modif 1988; 7: 359–64Google Scholar
  50. 50.
    Krown SE, Gold JWM, Medzwiecki D, et al. Interferon-α with zidovudine: safety, tolerance, and clinical and virological effects in patients with Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1990; 112: 812–21PubMedGoogle Scholar
  51. 51.
    Kovacs JA, Deyton L, Davey R, et al. Combined zidovudine and interferon-a therapy in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989; 111: 280–7PubMedGoogle Scholar
  52. 52.
    Harris JW, Berson AM, Reed TA, et al. Radiation therapy for Kaposi’s sarcoma in AIDS. In: Ziegler JL, Dorfman RF, editors. Kaposi’s sarcoma. New York: Marcel Dekker, 1988: 237–48Google Scholar
  53. 53.
    Hill DR. Role of radiation therapy for epidemic Kaposi’s sarcoma. Semin Oncol. 1987; 14 Suppl. 3: 19–22PubMedGoogle Scholar
  54. 54.
    Nobler MR. Pulmonary irradiation for Kaposi’s sarcoma in AIDS. Am J Clin Oncol 1985; 8: 441–4PubMedCrossRefGoogle Scholar
  55. 55.
    Chak LY, Gill PS, Levine AM, et al. Radiation therapy for acquired immunodeficiency syndrome-related Kaposi’s sarcoma. J Clin Oncol 1988; 6: 863–7PubMedGoogle Scholar
  56. 56.
    Newman S. Treatment of epidemic Kaposi’s sarcoma with in-tralesional yinblastine injection. Proc ASCO 1988; 7: 19Google Scholar
  57. 57.
    Boudreaux AA, Smith LL, Cosby CD, et al. Intralesional vin-blastine for cutaneous Kaposi’s sarcoma associated with acquired immunodeficiency syndrome: a clinical trial to evaluate efficacy and discomfort associated with injection. J Am Acad Dermatol 1993; 28: 61–5PubMedCrossRefGoogle Scholar
  58. 58.
    Epstein JB, Scully C. Intralesional vinblastine for oral Kaposi’s sarcoma in HIV infection. Lancet 2; 1100–1Google Scholar
  59. 59.
    Epstein J, Lozada-Nur F, McLeod WA, et al. Oral Kaposi’s sarcoma in acquired immunodeficiency syndrome: review of management and report of the efficacy of intralesional vinblastine. Cancer 1989; 64: 2424–30PubMedCrossRefGoogle Scholar
  60. 60.
    Tappero JW, Berger TG, Kaplan LD, et al. Cryotherapy for cutaneous Kaposi’s sarcoma associated with acquired immunodeficiency syndrome (AIDS): a phase II trial. J Acquir Immun Def Synd 1991; 4: 839–46Google Scholar
  61. 61.
    Tschechne B, von Wussow P, et al. High-dose intralesional re-combinant interferon-alpha-IIb treatment in HIV-1 infected patients with Kaposi’s sarcoma [abstract 2100]. Vlth International Conference on AIDS; 1990: San Francisco, 2: 379Google Scholar
  62. 62.
    Sulis E, Floris C, Sulis ML, et al. Interferon administered in-tralesionally in skin and oral cavity lesions in heterosexual drug addicted patients with AIDS-related Kaposi’s sarcoma. Eur J Cancer Clin Oncol 1988; 25: 759–61CrossRefGoogle Scholar
  63. 63.
    Shubik P. Vascularization of tumors: a review. J Cancer Res Clin Oncol 1982; 103: 211–26PubMedCrossRefGoogle Scholar
  64. 64.
    Davorak H, Nagy JA, Davorak JT, Davorak AM. Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules. Am J Path 1988; 133: 95–109Google Scholar
  65. 65.
    Seymour LW. Passive tumor targeting of soluble macromolecules and drug conjugates. Crit Rev Ther Drug Carrier Syst 1992; 9: 135–87PubMedGoogle Scholar
  66. 66.
    Vogel J, Henricks SH, Reynolds RK, et al. The HIV tat gene induces dermal lesions resembling Kaposi’s sarcoma in trans-genic mice. Nature 1988; 335: 606–11PubMedCrossRefGoogle Scholar
  67. 67.
    Presant CA, Blayney D, Proffitt RT, et al. Preliminary report: imaging of Kaposi’s sarcoma and lymphoma in AIDS with indium-111-labeled liposomes. Lancet 1990; 335: 1307–9PubMedCrossRefGoogle Scholar
  68. 68.
    Huang SK, Martin FJ, Jay G, et al. Extravasation and transcytosis of liposomes in Kaposi’s sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene. Am J Pathol 1993; 143: 10–14PubMedGoogle Scholar
  69. 69.
    Masood R, Husain SR, Rahman A, et al. Potentiation of cytotoxicity of Kaposi’s sarcoma related to immunodeficiency syndrome (AIDS) by liposome-encapsulated doxorubicin. AIDS Res Human Retrovir 1993; 9: 741–6CrossRefGoogle Scholar
  70. 70.
    Northfelt DW. Doxil™ (liposomal doxorubicin) delivers more doxorubicin to AIDS-Kaposi’s sarcoma (AIDS-KS) lesions than to normal skin. Proc ASCO 1994; 13: 51Google Scholar
  71. 71.
    Presant CA, Scolaro M, Kennedy P, et al. Liposomal dauno-rubicin treatment of HIV-associated Kaposi’s sarcoma. Lancet 1993; 341: 1242–3PubMedCrossRefGoogle Scholar
  72. 72.
    Hengge UR, Brockmeyer NH, Baumann M, et al. Liposomal doxorubicin in AIDS-related Kaposi’s sarcoma. Lancet 1993; 342: 497PubMedCrossRefGoogle Scholar
  73. 73.
    Poizot-Martin I, Giovanni M, Rosello R, et al. Liposomal-doxorubicin in human immunodeficiency virus-associated Kaposi’s sarcoma. J Clin Oncol 1994; 12: 645PubMedGoogle Scholar
  74. 74.
    Ensoli B, Nakamura S, Salahuddin SZ, et al. AIDS-Kaposi’s sarcoma-derived cells express cytokines with autocrine and paracrine growth effects. Science 1989; 243: 223–6PubMedCrossRefGoogle Scholar
  75. 75.
    Weindel K, Marme D, Weich HA. AIDS-associated Kaposi’s sarcoma cells in culture express vascular endothelial growth factor. Biochem Biophys Res Commun 1992; 189: 824–31CrossRefGoogle Scholar
  76. 76.
    Barillari G, Buonaguro L, Fiorelli V, et al. Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression. J Immunol 1992; 149: 3727–34PubMedGoogle Scholar
  77. 77.
    Herbert JM, Cottineau M, Driot F, et al. Activity of pentosan polysulphate and derived compounds on vascular endothelial cell proliferation and migration induced by acidic and basic FGF in vitro. Biochem Pharmacol 1988; 37: 4281PubMedCrossRefGoogle Scholar
  78. 78.
    Nakamura S, Sakurada SS, Salahuddin SZ, et al. Inhibition of development of Kaposi’s sarcoma-related lesions by a bacterial cell wall complex. Science 1992; 255: 1437–40PubMedCrossRefGoogle Scholar
  79. 79.
    Pluda JM, Shay LE, Foli A, et al. Administration of pentosan polysulfate to patients with human immunodeficiency virus-associated Kaposi’s sarcoma. J Natl Cancer Inst 1993; 85: 1585–92PubMedCrossRefGoogle Scholar
  80. 80.
    Plettenberg A, Stoehr A, van Dyk U, et al. Increasing risk for opportunistic infections (CDC IV Cl) during chemotherapy in patients with Kaposi’s sarcoma. Abstracts, IXth International Conference on AIDS; 1993; PO-B12: BerlinGoogle Scholar
  81. 81.
    Volberding PA, Kusick P, Feigal DW. Effect of chemotherapy for HIV-associated Kaposi’s sarcoma on long-term survival. Proc ASCO 1989; 8: 30Google Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Donald W. Northfelt
    • 1
  1. 1.Division of Hematology/ Oncology, Department of MedicineUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations