A risk and benefit assessment of treatment for AIDS-related Kaposi's sarcoma

Kaposi's sarcoma is the most common malignancy observed in patients with HI V-1 infection, and causes considerable morbidity and, when the lungs are in volved, mortality. Therapy should be based on an evaluation of prognostic f actors, in particular the extent and rate of tumour growth, patient symptom s, immune system condition and concurrent complications of AIDS. Neverthele ss, considering the palliative role of Kaposi's sarcoma therapy, the potent ial benefits of therapy must be weighed against the high risk of adverse ef fects. Therefore, quality of life assessment is an integral component of th erapeutic decisions. Localised Kaposi's sarcoma cutaneous tumours have been successfully treated with surgical excision, laser therapy, liquid nitrogen cryotherapy and rad iotherapy. In patients with moderately extensive cutaneous or mucosal disea se and CD4+ cell counts of greater than or equal to 2000/ml, immunotherapy and antiretroviral drugs are indicated. Preliminary results indicate that a ntiretroviral therapy might be effective and well tolerated in the treatmen t of less advanced Kaposi's sarcoma. In patients with aggressive and extensive mucocutaneous disease or with vis ceral manifestations of Kaposi's sarcoma, systemic cytotoxic therapy is ind icated. However, the optimal treatment has yet to be found. The combination of doxorubicin, bleomycin and vincristine (ABV) has produced high overall response rates and is indicated as first-line treatment for patients with l ife-threatening or visceral disease. In patients who are leucopenic and req uire chemotherapy, single or dual agents associated with lower myelotoxicit y [i.e. bleomycin, vincristine/vinblastine or a combination of bleomycin an d vincristine/vinblastine (BV)] are most widely used. Other effective cytot oxic regimens are liposomal anthracyclines, paclitaxel and vinorelbine. To date, 3 randomised trials have compared these drugs to ABV and BV. In a lar ge phase IU study, the efficacy of liposomal daunorubicin was comparable wi th that of ABV. In 2 phase III studies, liposomal doxorubicin was compared with ABV and BV regimens and was found to be significantly more effective i n producing objective responses. Therefore, liposomal doxorubicin, although more myelosuppressive than the BV regimen, is now considered by many physi cians as the first-line therapy in patients with advanced stage Kaposi's sa rcoma. Paclitaxel and vinorelbine have potential in Kaposi's sarcoma, but addition al studies are needed to evaluate different schedules and to compare their activity with that of the reference regimens. Institution or continuation of both effective antiretroviral therapy and pr ophylaxis of opportunistic infections should be recommended to all patients receiving systemic cytotoxic therapies. However, attention must be paid to the cross-toxicity and possible pharmacokinetic interactions between antir etrovirals and antineoplastics.