Long-term chemotherapy of HIV-associated Kaposi's sarcoma with liposomal doxorubicin
Introduction
Kaposi's sarcoma (KS) is a common acquired immunodeficiency syndrome (AIDS)-defining disease caused by human herpesvirus-8 (HHV-8) [1]. In general, KS occurs as multifocal mucocutaneous lesions and afflicts internal organs such as the lymph nodes, lungs or the gastrointestinal tract [2]. In the pre-highly active antiretroviral therapy (HAART) era, the survival of patients with AIDS-KS rarely exceeded 3 years 3, 4. The management of KS depends on the extent, the degree of immunodeficiency and the existence of opportunistic infections 2, 5. At present, there is no curative treatment for HIV-associated KS although immune reconstitution and antiviral approaches have been evaluated 6, 7. Consequently, there is a need for long-term maintenance therapy. The administration of conventional cytotoxic drugs is limited because of frequent adverse effects in HIV patients prone to immunodeficiency and recurrent infections. Pegylated liposomal doxorubicin (PegLiposomal DOX) represents an improved preparation with a prolonged plasma half-life (55 h) and a 19-fold higher concentration of doxorubicin in lesional tissue 8, 9.
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Patients
A total of 52 HIV patients with biopsy-proven KS received long-term chemotherapy (⩾18 weeks) with liposomal doxorubicin from July 1992 to March 1996. Eligibility criteria included advanced KS, as defined by disseminated mucocutaneous lesions with oedema or visceral manifestation, a Karnofsky performance score >50%, a white blood cell count >2×109/l, haemoglobin >100 g/l and platelets > 50×109/l. Patients with acute opportunistic infections, Non-Hodgkin's lymphoma or cardiac failure were
Patients
The majority of the 52 patients examined were Caucasian homosexual men (94%) with an average cluster of designation CD4 cell count of 75±106×106/l cells and a mean age of 41.7±10.6 years (Table 1). Based on the ACTG criteria, a poor risk for tumour burden (T3) was noted in 82.6% of the patient population. 94.2% were at poor risk for the immune system (I3). A poor risk for systemic illness (S3) at baseline was present in 69.2%.
Treatment and response
During a median observation period of 71±51 weeks (range 18–187
Discussion
Our study demonstrates a high response rate under long-term chemotherapy with liposomal doxorubicin for widespread KS in the pre-HAART era. Only 8 patients (15%) developed tumor progression during the 71±51 weeks observation period. These data are in agreement with previous publications, which were based on much shorter observation periods 5, 12, 13, 14, 15.
In our trial, most patients received a dose of 20 mg/m2 in 3-week intervals. The dose administered was lower than that reported by Bogner
Acknowledgements
We would like to thank Dr E. Stockfleth (University of Kiel) for performing the HHV-8 PCR. We also thank Hagen Apel for photographical assistance and Nicole-C. Bartosch for typing the manuscript.
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Long-term administration of pegylated liposomal doxorubicin at almost twice the recommended lifetime dose in 10 years without cardiotoxicity in a Japanese patient with HIV-associated Kaposi sarcoma
2020, Journal of Infection and ChemotherapyCitation Excerpt :One study reported a rare cardiac side effect confirmed by myocardial biopsy [14]. Another study analyzed not only cardiotoxicity but also other side effects leucopenia, neutropenia, anemia, and liver dysfunction of PLD and concluded the safety of PLD [15]. However, these studies were reported from Europe and the United States, and we were unable to find any reports of PLD administration in an Asian (Japanese) patient exceeding a cumulative dose of 550 mg/m2.
PD-1 blockade with nivolumab in endemic Kaposi sarcoma
2018, Annals of OncologyStealth anti-CD4 conjugated immunoliposomes with dual antiretroviral drugs - Modern Trojan horses to combat HIV
2015, European Journal of Pharmaceutics and BiopharmaceuticsCitation Excerpt :HAART alone is not solely efficient for the treatment of the HIV because there are other opportunistic infections like histoplasmosis, Kaposi’s sarcoma, tuberculosis, and pneumonia that accompany HIV infections due to the decrease in the number of the CD4 positive immune cells. Treatment with liposomal doxorubicin has been employed for reducing the tumor progression in HIV-associated Kaposi’s sarcoma, which is currently in the phase II clinical trials [18]. Thus a combined therapy of HAART drugs and other drugs are used for the treatment of HIV infections in conventional therapy.
A review of the efficacy and outcomes studies of currently approved chemotherapy treatments for advanced AIDS-Kaposi's sarcoma
2011, HIV and AIDS ReviewCitation Excerpt :To address the issue of toxicity and cardiotoxicity, liposomal covers were developed to provide a preferential delivery of the drug to tissues with new vascularisation (often around tumors), increasing the concentration of the drug in the tumor but reducing the exposure to normal tissue, decreasing toxicity and adverse effects [29]. Several phase II clinical trials were conducted to study the use of liposomal anthracyclines (PLD and DNX) in the treatment of systemic KS and showed that both drugs are effective (Table 1) [6–12]. Other studies include a comparison between liposomal anthracyclines and another cytostatic protocol (Table 2) [13,15,16,27].
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