Abstract
BackgroundPegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear.Case presentationA 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient’s left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2.ConclusionsThis case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.
Highlights
Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS)
A questionnaire surveillance study of HIVassociated KS in Japan showed that approximately 10% of patients had KS that was refractory to pegylated liposomal doxorubicin therapy combined with antiretroviral therapy (ART) [2]
In a trial for metastatic breast carcinoma, non-pegylated liposomal doxorubicin showed lesser cardiac toxicity than that of conventional doxorubicin; congestive heart failure (CHF) occurred in 2 and 8% of patients treated with non-pegylated liposomal doxorubicin and conventional doxorubicin, respectively [15]
Summary
Kaposi sarcoma (KS) is a major life-threatening complication associated with human immunodeficiency virus (HIV) infection. After 16 courses of pegylated liposomal doxorubicin, the cumulative dose was 320 mg/m2 His pleural effusion had decreased, and leg edema and skin nodules had gradually improved. In order to avoid cardiac toxicity associated with long-term use of pegylated liposomal doxorubicin, we switched his therapy to paclitaxel (100 mg/m2 every 2 weeks) His right pleural effusion increased rapidly after two courses of paclitaxel. Histological examination of his heart (Fig. 2) showed preservation of myofibrils and myocytes, with little inflammatory cell infiltration, corresponding to 0.5 points on the Billingham scale; a widely used endomyocardial biopsy score for grading anthra cycline-induced myocardial damage (Appendix) This finding indicated that he had not experienced histological cardiotoxicity as a result of the 980 mg/m2 cumulative dose of pegylated liposomal doxorubicin that he had received
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