Skip to main content
Log in

Liposomal doxorubicin in AIDS-related Kaposi's sarcoma: long-term experiences

  • Original Article
  • Published:
The clinical investigator Aims and scope Submit manuscript

Abstract

Treatment of AIDS-related Kaposi's sarcoma with cytotoxic chemotherapy is limited by toxicities of the various agents. Liposomal doxorubicin is a new treatment option for patients with Kaposi's sarcoma with potentially reduced toxicity. Three AIDS patients with different stages of tumor risk were enrolled in a study evaluating the safety and efficacy of liposomal doxorubicin at a dose of 10–20 mg/m2 every 2–4 weeks. Maximal duration of treatment was 86 weeks with a cumulative dose of 560 mg/m2. Criteria proposed by the AIDS Clinical Trials Group were used to define tumor stages and response to therapy. All patients showed partial responses after 40–100 mg/m2 total dose with reduction of tumor-associated edema and flattening of more than 50% of previously nodular or plaquelike lesions. One patient showed progressive disease after discontinuation of treatment for 8 weeks; Kaposi's sarcoma responded again partially on retreatment. Progression was also seen in one patient after dose reduction due to granulocytopenia and again during treatment of active cytomegalovirus retinitis. Serial measurements of cutaneous target lesion surface area did not indicate response. Increases in surface area, however, correlated with progressive disease. Toxicities included moderate leukopenia, aphthous stomatitis, and transient alopecia. Liposomal doxorubicin may well be valuable for long-term treatment of AIDS-associated Kaposi's sarcoma, especially in patients with extensive disease. However, controlled comparison with conventional treatment regimens is mandatory.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

ACTG:

AIDS Clinical Trials Group

GCSF:

granulocyte colony stimulating factor

KS:

Kaposi's sarcoma

PEG:

polyethylene glycol

S-DOX:

Stealth liposomal doxorubicin

TIS:

tumour/immune function/systemic illness

References

  1. Ahmad I, Allen TM (1992) Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro. Cancer Res 52:4817–4820

    Google Scholar 

  2. Allen TM, Chonn A (1987) Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett 223:42–46

    Google Scholar 

  3. Allen TM, Hansen C (1991) Pharmacokinetics of Stealth versus conventional liposomes: effect of dose. Biochim Biophys Acta 1068:133–141

    Google Scholar 

  4. Allen TM, Ryan JL, Papahadjopoulos D (1985) Gangliosides reduce leakage of aqueous-space markers from liposomes in the presence of human plasma. Biochim Biophys Acta 818:205–210

    Google Scholar 

  5. Allen TM, Hansen C, Rutledge J (1989) Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. Biochim Biophys Acta 981:27–35

    Google Scholar 

  6. Allen TM, Hansen C, Martin F, Redemann C, Yau Young A (1991) Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta 1066:29–36

    Google Scholar 

  7. Allen TM, Mehra T, Hansen C, Chin YC (1992) Stealth liposomes: an improved sustained release system for 1-beta-D-arabinofuranosylcytosine. Cancer Res 52:2431–2439

    Google Scholar 

  8. Bogner JR, Zietz C, Held M, Späthling S, Sandor P, Kronawitter U, Goebel FD (1993) Ultrasound as a tool to evaluate remission of cutaneous Kaposi's sarcoma. AIDS 7:1081–1085

    Google Scholar 

  9. Boyle MJ, Marshall NE, Dolan GM, Ryan S, Milliken ST, Cooper DA, Goldstein D (1993) A phase II study of Stealth liposomal doxorubicin HCl (S-DXR) in HIV-associated Kaposi's sarcoma (KS). IXth International Conference on AIDS 1:397 (Abstract)

    Google Scholar 

  10. Cowens JW, Creaven PJ, Greco WR, Brenner DE, Tung Y, Ostro M, Ginsberg R, Petrelli N (1993) Initial clinical (phase I) trial of TLC D-99 (doxorubicin encapsulated in liposomes). Cancer Res 53:2796–2802

    Google Scholar 

  11. Fan D, Bucana CD, O'Brian CA, Zwelling LA, Seid C, Fidler U (1990) Enhancement of murine tumor cell sensitivity to adriamycin by presentation of the drug in phosphatidylcholine-phosphatidylserine liposomes. Cancer Res 50:3619–3621

    Google Scholar 

  12. Fischl MA, Krown SE, O'Boyle KP, Mitsuyasu R, Miles S, Wernz JC, Volberding PA, Kahn J, Groopman JE, Feinberg J, Woody M, and the AIDS Clinical Trials Group (1993) Weekly doxorubicin in the treatment of patients with AIDS-related Kaposi's sarcoma. J Acquit Immune Defic Syndr 6:259–264

    Google Scholar 

  13. Forssen EA, Tökes ZA (1981) Use of anionic liposomes for the reduction of chronic doxorubicin-induced cardiotoxicity. Proc Natl Acad Sci USA 78:1873–1878

    Google Scholar 

  14. Gabizon AA (1992) Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. Cancer Res 52:891–896

    Google Scholar 

  15. Gabizon A, Goren D, Fuks Z, Meshorer A, Barenholz Y (1985) Superior therapeutic activity of liposome-associated Adriamycin in a murine metastatic tumor model. Br J Cancer 51:681–689

    Google Scholar 

  16. Gabizon A, Price DC, Huberty J, Bresalier RS, Papahadjopoulos D (1990) Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies. Cancer Res 50:6371–6378

    Google Scholar 

  17. Gill PS, Akil B, Colletti P, Rarick M, Loureiro C, Bernstein Singer M, Krailo M, Levine AM (1989) Pulmonary Kaposi's sarcoma: clinical findings and results of therapy. Am J Med 87:57–61

    Google Scholar 

  18. Gill PS, Rarick M, McCutchan JA, Slater L, Parker B, Muchmore E, Bernstein Singer M, Akil B, Espina BM, Krailo M, Levine A (1991) Systemic treatment of AIDS-related Kaposi's sarcoma: results of a randomized trial. Am J Med 90:427–433

    Google Scholar 

  19. Gill PS, Bernstein Singer M, Espina BM, Rarick M, Magy F, Montgomery T, Berry MS, Levine A (1992) Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte-macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi's sarcoma. AIDS 6:1477–1481

    Google Scholar 

  20. Goebel FD, Bogner JR, Späthling S, Held M, Sandor P, Rolinski B (1993) Efficacy and toxicity of liposomal doxorubicin in advanced AIDS-related Kaposi's sarcoma (KS). An open study. IXth International Conference on AIDS I:58 (Abstract)

    Google Scholar 

  21. Gompels MM, Hill A, Jenkins P, Peters B, Tomlinson D, Harris JR, Stewart S, Pinching AJ (1992) Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin. AIDS 6:1175–1180

    Google Scholar 

  22. Hengge UR, Brockmeyer NH, Baumann M, Reimann G, Goos M (1993) Liposomal doxorubicin in AIDS-related Kaposi's sarcoma. Lancet 342:497

    Google Scholar 

  23. Herman EH, Rahman A, Ferrans VJ, Vick JA, Schein PS (1983) Prevention of chronic doxorubicin caridotoxicity in beagles by liposomal encapsulation. Cancer Res 43:5427–5432

    Google Scholar 

  24. Huang SK, Martin FJ, Jay G, Vogel J, Papahadjopoulos D, Friend DS (1993) Extravasation and transcytosis of liposomes in Kaposi's sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene. Am J Pathol 143:10–14

    Google Scholar 

  25. Ireland Gill A, Espina BM, Akil B, Gill PS (1992) Treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma using bleomycin-containing combination chemotherapy regimens. Semin Oncol 19:32–36

    Google Scholar 

  26. Jablonowsky H, Szelényi H, Armbrecht C, Mauss S, Niederau C, Strohmeyer G (1993) Liposomal doxorubicin — a new formulation for the treatment of Kaposis's sarcoma: a study on safety and efficacy in AIDS patients. IXth International Conference on AIDS I:397 (Abstract)

    Google Scholar 

  27. Krown SE, Metroka C, Wernz JZ (1989) Kaposi's sarcoma in the acquired immunodeficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. J Clin Oncol 7:1201–1207

    Google Scholar 

  28. Krown SE, Myskowski PL, Paredes J (1992) Medical management of AIDS patients. Kaposi's sarcoma. Med Clin North Am 76:235–252

    Google Scholar 

  29. Laubenstein LJ, Krigel RL, Odajnyk CM, Hymes KB, Friedman-Kien A, Wernz JC, Muggia FM (1984) Treatment of epidemic Kaposi's sarkoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine. J Clin Oncol 2:1115–1120

    Google Scholar 

  30. Mintzer DM, Real FX, Jovino L, Krown SE (1985) Treatment of Kaposi's-sarcoma and thrombocytopenia with vincristine in patients with the acquired immunodeficiency syndrome. Ann Int Med 102:200–202

    Google Scholar 

  31. Niedt GW, Schinella RA (1985) Acquired immunodeficiency syndrome. Clinicopathological study of 56 autopsies. Arch Pathol Lab Med 109:727–734

    Google Scholar 

  32. Northfelt DW, Kahn JO, Volberding PA (1991) Treatment of AIDS-related Kaposi's sarcoma. Hematol Oncol Clin North Am 5:297–310

    Google Scholar 

  33. Papahadjopoulos D, Allen TM, Gabizon A, Mayhew E, Matthay K, Huang SK, Lee KD, Woodle MC, Lasic DD, Redemann C, Martin J (1991) Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA 88:11460–11464

    Google Scholar 

  34. Presant CA, Blayney D, Proffitt RT, Turner AF, Williams LE, Nadel HI, Kennedy P, Wiseman C, Gala K, Crossley RJ, Preiss SJ, Ksionski GE, Presant SL (1990) Preliminary report: imaging of Kaposi sarcoma and lymphoma in AIDS with indium-111-labelled liposomes. Lancet 335:1307–1309

    Google Scholar 

  35. Presant CA, Scolado M, Kennedy P, Blayney DW, Flanagan B, Lisak J, Presant J (1993) Liposomal daunorubicin treatment of HIV-associated Kaposis's sarcoma. Lancet 341:1242–1243

    Google Scholar 

  36. Rahman A, White G, More N, Schein PS (1985) Pharmacological, toxocological, and therapeutical evaluation of doxorubicin entrapped in cardiolipin liposomes. Cancer Res 45:796–803

    Google Scholar 

  37. Rahman A, Carmichael D, Harris M, Roh JK (1986) Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes. Cancer Res 46:2295–2299

    Google Scholar 

  38. Rahman A, Treat J, Roh JK, Potkul LA, Alvord WG, Forst D, Woolley PV (1990) A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin. J Clin Oncol 8:1093–1100

    Google Scholar 

  39. Rinehart JJ, Lewis RP, Balcerzak SP (1974) Adriamycin cardiotoxicyty in man. Ann Int Med 81:875–478

    Google Scholar 

  40. Schröder K, Garbe C, Waibel M, Reupke H, Detmar M, Dallenbach F, Orfanos CE (1993) Granulozyten-koloniestimulierender Faktor (GCSF) in der Behandlung von Patienten mit HIV-assoziiertem mukokutanen Kaposi-Sarkom. Hautarzt 43:700–706

    Google Scholar 

  41. Senior J, Crawley JCW, Gregoriadis G (1985) Tissue distribution of liposomes exhibiting long half-lives in the circulation after intraveneous injection. Biochim Biophys Acta 839:1–8

    Google Scholar 

  42. Vogel J, Hinrichs SH, Reynolds RK, Luciw PA, Jay G (1988) The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature 335:606–611

    Google Scholar 

  43. Volberding PA, Abrams DI, Conant M, Kaslow K, Vranizan K, Ziegler J (1985) Vinblastine therapy for Kaposi's sarcoma in aqcuired immuno-deficiency syndrome. Ann Int Med 103:335–338

    Google Scholar 

  44. Zou Y, Priebe W, Ling YH, Perez-Soler R (1993) Organ distribution and tumor uptake of annamycin, a new anthracycline derivative with high affinity for lipid membranes, entrapped in multilamellar vesicles. Cancer Chemother Pharmacol 32:190–196

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correspondence to: D. Wagner

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wagner, D., Kern, W. & Kern, P. Liposomal doxorubicin in AIDS-related Kaposi's sarcoma: long-term experiences. Clin Investig 72, 417–423 (1994). https://doi.org/10.1007/BF00180514

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00180514

Key words

Navigation