Long-term chemotherapy of HIV-associated Kaposi's sarcoma with liposomal doxorubicin

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Abstract

The aim of this study was to examine the outcome, adverse events and clinical complications of long-term chemotherapy with pegylated liposomal doxorubicin (PegLiposomal DOX) for human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) in the pre-highly active antirectroval therapy (HAART) era. A phase II study over a 4-year period in a tertiary care university hospital was carried out. 52 acquired immunodeficiency syndrome (AIDS)-patients with advanced KS received long-term chemotherapy (71±51 weeks) with a mean of 22.8±18.2 cycles and a mean cumulative liposomal doxorubicin dose of 456±364 mg/m2 (120–1040 mg/m2). Tumour burden, duration and dosage of PegLiposomal DOX, adverse events, opportunistic infections, immunological parameters and HIV load were measured. A complete (10%) or partial response (56%) was achieved while on chemotherapy. 10 patients (19%) showed stable disease. Tumour progression was observed in 8 patients (15%). Importantly, chemotherapy with PegLiposomal DOX was also successful after previous cytostatic therapy with bleomycin and vincristine. The most common adverse events included leucopenia, neutropenia, anaemia, and increased liver function tests. 34 patients (65%) developed new opportunistic infections and 29 patients (56%) died during the study period. To conclude, pegylated liposomal doxorubicin is a safe and effective drug for long-term chemotherapy of advanced (AIDS) KS without adverse effects on CD4 cell counts and HIV viral load.

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.

Section snippets

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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