PHASE-I AIDS CLINICAL-TRIALS GROUP(075) STUDY OF ADRIAMYCIN, BLEOMYCIN AND VINCRISTINE CHEMOTHERAPY WITH ZIDOVUDINE IN THE TREATMENT OF AIDS-RELATED KAPOSIS-SARCOMA

Objective: To determine the toxicity and maximum tolerated dose of dox orubicin (adriamycin) in combination with fixed doses of bleomycin, vi ncristine (ABV) and zidovudine in patients with advanced AIDS-related Kaposi's sarcoma. Patients and methods: Twenty-six HIV-seropositive me n with Kaposi's sarcoma were treated daily with 100mg zidovudine orall y every 4h, along with combination chemotherapy using bleomycin 10 U/m (2) and vincristine 1.4mg/m(2) (maximum, 2mg) given intravenously in 2 -week cycles. In addition, three successive cohorts of eight patients received escalating doses of doxorubicin each beginning with no doxoru bicin (level I), doses of 10mg/m(2) (level II), and 15mg/m(2) (level I II). Results: The major dose-limiting toxicity experienced with the co mbination therapy was severe neutropenia in eight patients, four of wh om received level III doxorubicin (15mg/m(2)). Therefore, 10mg/m(2) of doxorubicin in combination with zidovudine and BV chemotherapy was de fined as the maximum tolerated dose. Other dose-limiting toxicities in cluded neuropathy (n = 2), cutaneous toxicity associated with bleomyci n (n = 1), and diarrhea (n = 1). Seventeen patients (71%; 95% confiden ce interval, 46-85) experienced either partial (n = 13) or clinical co mplete remission (n = 4) to therapy after a median of five cycles (ran ge, 2-9). Conclusion: The maximum tolerated dose of doxorubicin is 10m g/m(2) when given in combination with zidovudine and BV chemotherapy. Response rats observed with the combined antiretroviral and chemothera py regimen are similar to those previously reported with ABV chemother apy alone.