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Polyethylene Glycol-Liposomal Doxorubicin

A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in the Management of AIDS-Related Kaposi’s Sarcoma

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Summary

Synopsis

Doxorubicin is an antineoplastic drug which has in vitro and in vivo activity against a number of malignancies including Kaposi’s sarcoma. Incorporation of doxorubicin into polyethylene glycol— coated (pegylated) liposomes alters the pharmacokinetics of the drug. Liposomal doxorubicin has a smaller volume of distribution and slower plasma clearance than standard free doxorubicin. The liposomal formulation achieves higher concentrations in the highly vascularised lesions of Kaposi’s sarcoma than in normal tissue.

Liposomal doxorubicin monotherapy in patients with AIDS-related Kaposi’s sarcoma produced overall response rates (complete plus partial) of 43 and 59% in large comparative studies and 67 to 100% in noncomparative studies which included ≥ 20 patients. In comparative studies, liposomal doxorubicin was significantly more effective than the combination of standard doxorubicin, bleomycin and vincristine (overall response rates of 43 and 25%, respectively) and bleomycin and vincristine (BV) [overall response rates of 59 and 23%, respectively]. In addition, overall response rates to the liposomal drug were higher in both treatment arms of 2 smaller comparative studies which compared liposomal doxorubicin with BV, but significant between-treatment differences were not detected. Patient numbers in these 2 studies, however, may have been too small to detect significant differences.

Liposomal doxorubicin is generally well tolerated. Myelosuppression is the most common dose-limiting adverse effect in patients with AIDS and Kaposi’s sarcoma. Neutropenia occurs most often; anaemia and thrombocytopenia occur less frequently, as do nausea and vomiting and stomatitis. Palmar-plantar erythrodysaesthesia occurs in some patients, most commonly after 6 to 8 weeks of chemotherapy. Although symptoms may occasionally be severe, the syndrome usually does not require dosage reduction or treatment delay. Limited data suggest that the incidence of cardiotoxicity may be lower after liposomal doxorubicin than after equivalent doses of standard doxorubicin.

Overall, liposomal doxorubicin appears to be one of the most active single agents available for treating patients with AIDS-related Kaposi’s sarcoma. The therapeutic potential of liposomal doxorubicin administered in combination with other active agents to patients with Kaposi’s sarcoma is, as yet, unknown. However, administered alone, the drug seems to be more effective than the best available combination chemotherapy regimens.

Pharmacodynamic Properties

Doxorubicin is an anthracycline cytostatic antibiotic with activity against a variety of malignancies including Kaposi’s sarcoma. In vitro and in vivo, polyethylene glycol-coated (pegylated) liposomal doxorubicin inhibits the growth of Kaposi’s sarcoma cells. Kaposi’s sarcoma spindle cell cultures were more sensitive to liposomal doxorubicin than cultures of normal monocytes, or normal endothelial or smooth muscle cells.

Tumour cell DNA fragmentation induced by doxorubicin is a result of topoisomerase II inhibition which occurs when the drug intercalates between DNA strands. Antitumour activity and drug toxicity may also relate to the formation of intracellular oxygen free radicals, which are produced by reduction of the doxorubicin molecule. In addition, liposomal doxorubicin induces expression of monocyte chemoattractant protein-1, which results in intralesional recruitment of phagocytic cells in patients with Kaposi’s sarcoma.

Pharmacokinetic Properties

The pharmacokinetic profile of liposomal doxorubicin is substantially different from that of standard free doxorubicin. Compared with standard doxorubicin, the liposomal product distributes in a smaller volume (254 vs 4.1L), has a larger area under the plasma concentration-time curve and is cleared from the body more slowly (total plasma clearance 45.3 vs 0.08 L/h). In biopsy specimens obtained 48 and 96 hours after administration of liposomal doxorubicin to patients with AIDS-related Kaposi’s sarcoma, higher drug concentrations were present in Kaposi’s sarcoma lesions than in normal skin tissue.

The distribution half-life of liposomal doxorubicin is approximately 45 to 56 hours. Metabolites, including doxorubicinol, were detected in the urine, but not the plasma, of liposomal doxorubicin-treated patients, indicating that the metabolism of liposomal doxorubicin is similar to that of the free drug but that the rate of metabolite excretion is higher than the rate of metabolism. The effect of hepatic dysfunction on the clearance of liposomal doxorubicin is unclear; however, volume of distribution, clearance and elimination half-life in patients with mild to moderate hepatic dysfunction did not appear to be altered compared with values from historical controls.

Therapeutic Efficacy

Clinical studies of liposomal doxorubicin in Kaposi’s sarcoma predominantly included men with AIDS, CD4+ counts <200 cells/μl and good performance status. Most patients were classified according to AIDS Clinical Trials Group (ACTG) criteria as ‘poor risk’.

Liposomal doxorubicin is a highly active single agent in these patients. Overall response rates (complete plus partial) of 43 and 59% have been reported in large comparative trials. In noncomparative studies which included ≥20 patients and predominantly assessed liposomal doxorubicin 20 mg/m2 administered at 2- or 3-week intervals, overall response rates of 67 to 100% were reported. In the largest noncomparative study (n=238; overall response rate 81 %), no correlation was detected between response and CD4+ cell count, neutrophil count or ACTG risk category. Median quality-of-life scores improved during treatment in 2 studies which included prospective quality-of-life analysis.

Liposomal doxorubicin produced better response rates than bleomycin and vincristine (BV) or standard doxorubicin plus bleomycin and vincristine (ABV) in 4 studies. In the 2 largest studies (n=218 and 225), liposomal doxorubicin was significantly more effective than ABV (response rates of 43 and 25%, respectively) or BV (59 and 23%, respectively). Extensive and progressive baseline disease in patients in these studies and/or more rigorously applied response criteria may have contributed to the low overall response rates observed in both treatment arms. More liposomal doxorubicin-than BV-treated patients completed 6 cycles of chemotherapy. Compared with these 2 large studies, response rates in 2 smaller studies which compared liposomal doxorubicin with BV chemotherapy in patients with Kaposi’s sarcoma were higher, but significant between-treatment differences were not observed. Patient numbers in the latter 2 studies may have been too small to detect significant differences. The reported duration of response to liposomal doxorubicin in the 2 largest comparative studies was 15 and 20 weeks. Between-treatment differences in response duration were not detected in any study.

Tolerability

Liposomal doxorubicin is generally well tolerated. The most common dose-limiting adverse effect of the drug in patients with AIDS and Kaposi’s sarcoma is myelosuppression. At recommended dosages, neutropenia occurred in 50% of patients; severe neutropenia (<0.5 × 109 cells/L) occurred in 14%. However, pre-existing immune system compromise complicates assessment of neutropenia and infectious events in patients with AIDS. Anaemia occurred in 19% of patients.

Palmar-plantar erythrodysaesthesia, characterised by ulceration, erythema and desquamation on the palms of the hands and soles of the feet with pain and inflammation, occurs in some patients, most commonly after 6 to 8 weeks of treatment. At recommended dosages of liposomal doxorubicin, the incidence of this syndrome is <5%. Although reactions may occasionally be severe and debilitating, they are more often mild; most patients with the syndrome do not require dosage reduction or prolonged treatment delay.

Few data are available on the cardiac tolerability of liposomal doxorubicin. Although left ventricular failure has been reported in patients who received a high cumulative liposomal doxorubicin dose, some evidence suggests that the incidence and severity of this effect are lower than after similar doses of standard doxorubicin.

Nausea was reported in 17 to 31% of patients; vomiting occurred in approximately 8% of patients. WHO grade III or IV nausea and vomiting occurred in approximately 5% of liposomal doxorubicin-treated patients in 1 study. Some patients experience acute hypersensitivity reactions during the initial few minutes of the first infusion of liposomal doxorubicin, but these reactions often do not prevent further treatment with the drug. Patients who do not experience infusion reactions during the first cycle of liposomal doxorubicin are unlikely to react to subsequent cycles. In contrast to standard doxorubicin, extravasation of liposomal doxorubicin has been associated with only transient and mild local irritation.

Compared with BV chemotherapy, liposomal doxorubicin was associated with higher rates of myelosuppression and opportunistic infection, but lower rates of peripheral nerve toxicity. Limited data suggest that, when haemopoietic growth factor administration is permitted, myelosuppression is similar after liposomal doxorubicin and ABV chemotherapy.

Dosage and Administration

For patients with AIDS-related Kaposi’s sarcoma, the recommended dosage of liposomal doxorubicin (expressed in terms of doxorubicin content) is 20 mg/m2 every 3 weeks as long as response continues. In several large clinical studies, liposomal doxorubicin was administered at 2-week intervals. Dosage reduction is suggested for patients with treatment-limiting neutropenia, stomatitis or palmar-plantar erythrodysaesthesia.

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References

  1. Balmer C, Valley AW. Basic principles of cancer treatment and cancer chemotherapy. In: DiPiro JT, Talbert RL, Hayes PE, et al., editors. Pharmacotherapy: a pathophysiologic approach. 2nd ed. Norwalk Connecticut: Appleton & Lange, 1993: 1879–929

    Google Scholar 

  2. Sugarman SM, Perez-Soler R. Liposomes in the treatment of malignancy: a clinical perspective. Crit Rev Oncol Hematol 1992; 12: 231–42

    Article  PubMed  CAS  Google Scholar 

  3. Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA 1991; 88: 11460–4

    Article  PubMed  CAS  Google Scholar 

  4. Gabizon AA. Liposomal anthracyclines. Hematol Oncol Clin North Am 1994 Apr; 8: 431–50

    PubMed  CAS  Google Scholar 

  5. Gabizon A, Chemla M, Tzemach D, et al. Liposome longevity and stability in circulation: effects on the in vivo delivery to tumors and therapeutic efficacy of encapsulated anthracyclines. J Drug Target 1996; 3(5): 391–8

    Article  PubMed  CAS  Google Scholar 

  6. Lasic DD, Martin FJ, Gabizon A, et al. Sterically stabilised liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim Biophys Acta 1991; 1070: 187–92

    Article  PubMed  CAS  Google Scholar 

  7. Gabizon A, Isacson R, Libson E, et al. Clinical studies of liposome-encapsulated doxorubicin. Acta Oncol 1994; 33(7): 779–86

    Article  PubMed  CAS  Google Scholar 

  8. 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 May–Aug; 145: 261–9

    Article  PubMed  Google Scholar 

  9. Williams SS, Alosco TR, Mayhew E, et al. Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes. Cancer Res 1993 Sep 1; 53: 3964–7

    PubMed  CAS  Google Scholar 

  10. Vaage J, Donovan D, Mayhew E. Therapy of human ovarian carcinoma xenografts using doxorubicin encapsulated in sterically stabilized liposomes. Cancer 1993 Dec 15; 72: 3671–5

    Article  PubMed  CAS  Google Scholar 

  11. Vaage J, Barberá-Guillem E, Abra R, et al. Tissue distribution and therapeutic effect of intravenous free or encapsulated liposomal doxorubicin on human prostate carcinoma xenografts. Cancer 1993; 73: 1478–784

    Article  Google Scholar 

  12. Logan DM, Fillion LG, Gaudreault R, et al. The effect of daunorubicin (Dauno) or doxorubicin (Doxo) on epidemic Kaposi’s sarcoma (EKS) derived cell cultures [abstract no. W.A.1030]. VIIth International Conference on AIDS, 1991 Jun 16–21, Florence, Italy: 99

  13. Budach W, Budach V, Stuschke M, et al. Efficacy of ifosfamide, dacarbazine, doxorubicin and cisplatin in human sarcoma xenografts. Br J Cancer 1994; 70: 29–34

    Article  PubMed  CAS  Google Scholar 

  14. Amantea MA, Forrest A, DuMond C, et al. Population PK and PD of liposomal doxorubicin (LD) in HIV-infected patients (PTS) with Kaposi’s sarcoma (KS) [abstract no, PI-82A]. Clin Pharmacol Ther 1995 Feb; 57: 155

    Google Scholar 

  15. Northfelt DW, Martin FJ, Working P, et al. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi’s sarcoma. J Clin Pharmacol 1996 Jan; 36: 55–63

    PubMed  CAS  Google Scholar 

  16. Northfelt DW, Martin FJ, Kaplan LD, et al. Pharmacokinetics (PK), tumor localization (TL), and safety of Doxil™ (liposomal doxorubicin) in AIDS patients with Kaposi’s sarcoma (AIDS-KS) [abstract no.8]. Proc Am Soc Clin Oncol 1993 Mar; 12: 51

    Google Scholar 

  17. Gabizon A, Catane R, Uziely B, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 1994 Feb 15; 54: 987–92

    PubMed  CAS  Google Scholar 

  18. Greene RF, Collins JM, Jenkins JF, et al. Plasma pharmacokinetics of Adriamycin and adriamycinol: implications for the design of in vitro experiments and treatment protocols. Cancer Res 1983; 43: 3417–21

    PubMed  CAS  Google Scholar 

  19. Speth PAJ, van Hoesel QGCM, Haanen C. Clinical pharmacokinetics of doxorubicin. Clin Pharmacokinet 1988; 15: 15–31

    Article  PubMed  CAS  Google Scholar 

  20. Gabizon AA, Barenholz Y, Bialer M. Prolongation of the circulation time of doxorubicin encapsulated in liposomes containing a polyethylene glycol-derivatized phospholipid: pharmacokinetic studies in rodents and dogs. Pharm Res 1993 May; 10: 703–8

    Article  PubMed  CAS  Google Scholar 

  21. Harrington KJ, Gooden CSR, Mohammedtaghi S, et al. Biodistribution and pharmacokinetics of In-111-labeled Stealth® liposomes in patients with solid tumours [abstract no. 1511]. Proc Am Soc Clin Oncol 1996; 15: 477

    Google Scholar 

  22. Allen TM. Long-circulating (sterically stabilized) liposomes for targeted drug delivery. Trends Pharmacol Sci 1994 Jul; 15: 215–20

    Article  PubMed  CAS  Google Scholar 

  23. Huang SK, Lee K-D, Hong K, et al. Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res 1992; 52: 5135–43

    PubMed  CAS  Google Scholar 

  24. Wang C-YE, Schroeter AL, Su WPD. Acquired immunodeficiency syndrome-related Kaposi’s sarcoma. Mayo Clin Proc 1995 Sep; 70: 869–79

    PubMed  CAS  Google Scholar 

  25. Northfelt DW Stealth® liposomal doxorubicin (SLD) delivers more doxorubicin (DOX) to AIDS-Kaposi’s sarcoma (AIDS-KS) lesions than to normal skin [abstract no. 5]. Proc Am Soc Clin Oncol 1994 Mar; 13: 51

    Google Scholar 

  26. Robert J, Vrignaud P, Nguyen-Ngoc T, et al. Comparative pharmacokinetics and metabolism of doxorubicin and epirubicin in patients with metastatic breast cancer. Cancer Treat Rep 1985; 69(6): 633–40

    PubMed  CAS  Google Scholar 

  27. Rahman A, Treat J, Roh J-K, et al. A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin. J Clin Oncol 1990 Jun; 8: 1093–100

    PubMed  CAS  Google Scholar 

  28. Cowens JW, Creaven PJ, Greco WR, et al. Initial clinical (phase I) trial of TLC D-99 (doxorubicin encapsulated in liposomes). Cancer Res 1993; 53: 2796–802

    PubMed  CAS  Google Scholar 

  29. Gabizon A, Chisin R, Amselem S, et al. Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin. Br J Cancer 1991 Dec; 64: 1125–32

    Article  PubMed  CAS  Google Scholar 

  30. Venook AP, Amantea M, Bonnern E, et al. Pegylated liposome-encapsulated doxorubicin (Doxil®) in patients with hepatocellular carcinoma (HCC) [abstract no. 1494]. Proc Am Soc Clin Oncol 1996; 15: 473

    Google Scholar 

  31. Uziely B, Jeffers S, Isacson R, et al. Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies. J Clin Oncol 1995 Jul; 13: 1777–85

    PubMed  CAS  Google Scholar 

  32. Muggia F, Hainsworth J, Jeffers S, et al. Liposomal doxorubicin (Doxil) is active against refractory ovarian cancer [abstract no. 781]. Proc Am Soc Clin Oncol 1996; 15: 287

    Google Scholar 

  33. Ranson M, O’Byrne K, Carmichael J, et al. Phase II dose-finding trial of DOX-SL™ (Stealth®) liposomal doxorubicin HCL) in the treatment of advanced breast cancer [abstract no. 161]. Proc Am Soc Clin Oncol 1996; 15: 124

    Google Scholar 

  34. Ockenfels HM, Brockmeyer NH, Hengge U, et al. Cutaneous angiosarcoma: a novel therapy with liposomal doxorubicin? J Eur Acad Dermatol Venereol 1996; 6: 71–5

    Article  Google Scholar 

  35. Goebel F-D, Goldstein D, Goos M, et al. Efficacy and safety of Stealth® liposomal doxorubicin in AIDS-related Kaposi’s sarcoma. Br J Cancer 1996 Apr; 73: 989–94

    Article  PubMed  CAS  Google Scholar 

  36. Bogner JR, Kronawitter U, Rolinski B, et al. Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma. J Acquir Immune Defic Syndr 1994 May; 7: 463–8

    PubMed  CAS  Google Scholar 

  37. Boyle MJ, Marshall NE, Dolan GM, et al. A phase II study of Stealth liposomal doxorubicin HCL (S-DXR) in HIV-associated Kaposi’s sarcoma [abstract no. PO-B12-1570]. 9th International Conference on AIDS; 1993 Jun 6–11; Berlin, Germany; vol. 1: 397

    Google Scholar 

  38. Hengge UR, Brockmeyer NH, Baumann M, et al. Liposomal doxorubicin in AIDS-related Kaposi’s sarcoma [letter]. Lancet 1993 Aug 21; 342: 497

    Article  PubMed  CAS  Google Scholar 

  39. Thommes J, Northfelt D, Rios A, et al. Open-label trial of Stealth® liposomal doxorubicin (D-SL) in the treatment of moderate to severe AIDS-related Kaposi’s sarcoma (AIDS-KS) [abstract no. 24]. Proc Am Soc Clin Oncol 1994 Mar; 13: 55

    Google Scholar 

  40. Northfelt DW, Dezube B, Miller B, et al. Randomized comparative trial of Doxil vs. Adriamycin, bleomycin, and vincristine (ABV) in the treatment of severe AIDS-related Kaposi’s sarcoma (AIDS-KS) [abstract no. 1515]. Blood 1995; 86(10) Suppl. 1: 382a

    Google Scholar 

  41. Stewart JSW, Jablonowski H, Goebel FD, et al. A randomised comparative trial of DOXIL® versus bleomycin and vincristine (BV) in the treatment of AIDS-related Kaposi’s sarcoma. SEQUUS Pharmaceuticals (London), 1996 (Data on file)

  42. Harrison M, Denton A, Tomlinson D, et al. AIDS related Kaposi’s sarcoma: comparison of liposomal entrapped doxorubicin (LED) with bleomycin and vincristine (BV) [abstract no. O35]. Br J Cancer 1995 Jul; 72 Suppl. 25: 12

    Google Scholar 

  43. Harrison M, Tomlinson D, Stewart S. Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi’s sarcoma. J Clin Oncol 1995 Apr; 13(4): 914–20

    PubMed  CAS  Google Scholar 

  44. Jablonowski H, Boden D, Häussinger D. Long term use of DOX-SL™ (Stealth® liposomal doxorubicin HC1) in the treatment of moderate to severe AIDS-related Kaposi’s sarcoma [abstract no. 842]. Proc Am Soc Clin Oncol 1996; 15: 303

    Google Scholar 

  45. Krown SE, Metroka C, Wernz JC, et al. Kaposi’s sarcoma in the aquired immune deficiency sydrome: a proposal for uniform evaluation, response, and staging criteria. J Clin Oncol 1989; 7(9): 1201–7

    PubMed  CAS  Google Scholar 

  46. Krown SE, Testa M, Huang J. Validation of the AIDS Clinical Trials Group (ACTG) staging classification for AIDS-associated Kaposi’s sarcoma (AIDS/KS) [abstract no. 844]. Proc Am Soc Clin Oncol 1996; 15: 303

    Google Scholar 

  47. Esser S, Bleil M, Reimann G, et al. Long term treatment with liposomal doxorubicin in patients with AIDS-related Kaposi’s sarcoma [abstract no. Th.A.4077]. 11th International Conference on AIDS; 1996 Jul 7–12: Vancouver, Canada. Transcontinental Printing, 1996: 266

  48. Rizzardini G, Vigevani GM, Cremoni L, et al. Liposomal doxorubicin (LD) or bleomycin plus vincristine (BV) in epidemic Kaposi’s sarcoma (KS) [abstract no. 2173]. Can J Infect Dis 1995 Jul; 6 Suppl. C: 371C

    Google Scholar 

  49. Volm MD, Von Roenn JH. Treatment strategies for epidemic Kaposi’s sarcoma. Curr Opin Oncol 1995 Sep; 7: 429–36

    Article  PubMed  CAS  Google Scholar 

  50. Bergin C, O’Leary A, McCreary C, et al. Treatment of Kaposi’s sarcoma with liposomal doxorubicin. Am J Health System Pharm 1995 Sep 15; 52: 2001–4

    CAS  Google Scholar 

  51. James ND, Coker RJ, Tomlinson D, et al. Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi’s sarcoma in AIDS. Clin Oncol 1994; 6: 294–6

    Article  CAS  Google Scholar 

  52. Milazzo F, Rizzardini G, Capetti A, et al. Efficacy and toxicity of Doxil (Stealth liposomal doxorubicin HCL) in moderate/severe epidemic Kaposi’s sarcoma [abstract]. AIDS 1994 Nov; 8 Suppl. 4: S46

    Article  Google Scholar 

  53. Simpson JK, Miller RF, Spittle MF. Liposomal doxorubicin for treatment of AIDS-related Kaposi’s sarcoma. Clin Oncol 1993; 5: 372–4

    Article  CAS  Google Scholar 

  54. Wagner D, Kern WV, Kern P. Liposomal doxorubicin in AIDS-related Kaposi’s sarcoma: long-term experiences. Clin Investig 1994 Jun; 72: 417–23

    PubMed  CAS  Google Scholar 

  55. Goebel F-D, Gruenaug M, Bogner JR. Survival times of patients with AIDS-related Kaposi’s sarcoma with pulmonary involvement using liposomal doxorubicin [abstract no. 860]. Proc Am Soc Clin Oncol 1996; 15: 307

    Google Scholar 

  56. Dezube BJ. Safety assessment: Doxil® (doxorubicin HCl liposome injection) in refractory AIDS-related Kaposi’s sarcoma. Doxil® Clinical Series.Vol. 1, No. 2; SEQUUS Pharmaceuticals, Inc., Menlo Park, California, 1996.

  57. 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: 427–33

    PubMed  CAS  Google Scholar 

  58. Berry G, Billingham M, Alderman E, et al. Reduced cardiotoxicity of DOXIL (pegylated liposomal doxorubicin) in AIDS Kaposi’s sarcoma patients compared to a matched control group of cancer patients given doxorubicin [abstract no. 843]. Proc Am Soc Clin Oncol 1996; 15: 303

    Google Scholar 

  59. Madhavan S, Northfelt DW. Lack of vesicant injury following extravasation of liposomal doxorubicin [letter]. J Natl Cancer Inst 1995 Oct 18; 87: 1556–7

    Article  PubMed  CAS  Google Scholar 

  60. Madhavan S, Northfelt DW. Lack of vesicant injury following extravasation of liposomal doxorubicin [abstract]. Breast Cancer Res Treat 1996; 37 Suppl.: 77

    Article  Google Scholar 

  61. Hengge UR, Brockmeyer NH, Rasshofer R, et al. Fatal hepatic failure with liposomal doxorubicin [letter]. Lancet 1993 Feb 6; 341: 383–4

    Article  PubMed  CAS  Google Scholar 

  62. Coker RJ, James ND, Stewart JSW. Hepatic toxicity of liposomal encapsulated doxorubicin [letter]. Lancet 1993 Mar 20; 341: 756 au63._SEQUUS Pharmaceuticals Inc. Doxil® prescribing information. Menlo Park, California, USA, 1995.

    Article  PubMed  CAS  Google Scholar 

  63. Harrison M, Harrington KJ, Stewart JSW. Liposomal chemotherapy for AIDS-related Kaposi’s sarcoma. Expert Opin Invest Drug 1995 Dec; 4: 1197–203

    Article  CAS  Google Scholar 

  64. Lilenbaum RC, Ratner L. Systemic treatment of Kaposi’s sarcoma: current status and future directions. AIDS 1994 Feb; 8: 141–51

    Article  PubMed  CAS  Google Scholar 

  65. Gao S-J, Kingsley L, Hoover DR, et al. Seroconversion to antibodies against Kaposi’s sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi’s sarcoma. N Engl J Med 1996 Jul 25; 335: 233–41

    Article  PubMed  CAS  Google Scholar 

  66. Presant CA, Scolaro M, Kennedy P, et al. Liposomal daunorubicin treatment of HIV-associated Kaposi’s sarcoma. Lancet 1993; 341: 1242–3

    Article  PubMed  CAS  Google Scholar 

  67. Northfelt DW. Treatment of Kaposi’s sarcoma: current guidelines and future perspectives. Drugs 1994 Oct; 48: 569–82

    Article  PubMed  CAS  Google Scholar 

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    Allan J. Coukell & Caroline M. Spencer

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Various sections of the manuscript reviewed by: T.M. Allen, Department of Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada; G.J. Berry, Laboratory of Surgical Pathology, Stanford University Medical Center, Stanford, California, USA; J. Bogner, Medizinische Poliklinik, Klinikum Innenstadt der Ludwig-Maximilians— Universität München, Munich, Germany; A.A. Gabizon, Department of Oncology, Hadassah Medical Center, Jerusalem, Israel; F.-D. Goebel, Medizinische Poliklinik, Klinikum Innenstadt der Ludwig-Maximilians— Universität München, Munich, Germany; M. Harrison, Clare Hall Laboratories, Imperial Cancer Research Fund, South Mimms, England; S.E. Krown, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; H.I. Maibach, Department of Dermatology, University of California in San Francisco School of Medicine, San Francisco, California, USA; K. Maruyana, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan; F. Milazzo, Divisione Malattie Infettive e Servizio di Allergologia, Ospedale Luigi Sacco, Milan, Italy; G. Rizzardini, Divisione Malattie Infettive e Servizio di Allergologia, Ospedale Luigi Sacco, Milan, Italy; Y. Sadzuka, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka-ken, Japan; G. Storm, Department of Pharmaceutics, Faculty of Pharmacy, Universiteit Utrecht, Utrecht, The Netherlands; J.H. Von Roenn, Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA.

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Coukell, A.J., Spencer, C.M. Polyethylene Glycol-Liposomal Doxorubicin. Drugs 53, 520–538 (1997). https://doi.org/10.2165/00003495-199753030-00011

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