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 doxorubicin (adriamycin) in combination with fixed doses of bleomycin, vincristine (ABV) and zidovudine in patients with advanced AIDS-related Kaposi's sarcoma. Patients and methods: Twenty-six HIV-seropositive men with Kaposi's sarcoma were treated daily with 100mg zidovudine orally 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 doxorubicin (level I), doses of 10mg/m(2) (level II), and 15mg/m(2) (level III). Results: The major dose-limiting toxicity experienced with the combination therapy was severe neutropenia in eight patients, four of whom received level III doxorubicin (15mg/m(2)). Therefore, 10mg/m(2) of doxorubicin in combination with zidovudine and BV chemotherapy was defined as the maximum tolerated dose. Other dose-limiting toxicities included neuropathy (n = 2), cutaneous toxicity associated with bleomycin (n = 1), and diarrhea (n = 1). Seventeen patients (71%; 95% confidence interval, 46-85) experienced either partial (n = 13) or clinical complete remission (n = 4) to therapy after a median of five cycles (range, 2-9). Conclusion: The maximum tolerated dose of doxorubicin is 10mg/m(2) when given in combination with zidovudine and BV chemotherapy. Response rats observed with the combined antiretroviral and chemotherapy regimen are similar to those previously reported with ABV chemotherapy alone.