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Primary: To evaluate the safety, toxicity, and antitumor activity of two doses of interferon alfa-2b (IFN-alpha) combined with a fixed dose of didanosine (ddI) in patients with Kaposi's sarcoma associated with HIV infection. Secondary: To evaluate the effects of combined IFN-alpha and ddI treatment on HIV expression and markers of immune function. Previous studies have shown that IFN-alpha can induce regression of Kaposi's sarcoma and suppression of HIV in some patients. Although various trials using IFN-alpha in combination with the nucleoside analogue zidovudine have demonstrated a high degree of antitumor activity and evidence of HIV suppression, the overlapping toxicity (primarily neutropenia) of these two agents has proven dose-limiting. The toxicity profile of ddI suggests that this drug may be better tolerated than zidovudine when combined with IFN-alpha. Previous studies have shown that IFN-alpha can induce regression of Kaposi's sarcoma and suppression of HIV in some patients. Although various trials using IFN-alpha in combination with the nucleoside analogue zidovudine have demonstrated a high degree of antitumor activity and evidence of HIV suppression, the overlapping toxicity (primarily neutropenia) of these two agents has proven dose-limiting. The toxicity profile of ddI suggests that this drug may be better tolerated than zidovudine when combined with IFN-alpha. Up to 90 patients are randomized to receive either low or high doses of IFN-alpha (1 or 10 million Units/day) in combination with a fixed dose of ddI. Fourteen patients are initially entered at each dose level. If no objective antitumor responses are observed among the first 14 patients at a given dose, no further patients are entered on that treatment arm. If one or more antitumor responses are seen at a given dose, up to 45 patients may be entered on that treatment arm. Patients must complete at least 4 weeks of study therapy to be considered evaluable for tumor response. Treatment is continued until tumor progression or unacceptable toxicity occurs. PER AMENDMENT 9/19/96: NOTE - After 16 weeks of treatment subjects may receive any FDA approved antiretroviral drug regimen in addition to or in place of ddI.
Inclusion Criteria Concurrent Medication: Allowed: * Chemoprophylaxis for candidiasis and herpes simplex. * Up to 14 days of metronidazole. * Recombinant erythropoietin. * G-CSF (for severe cases of neutropenia). * Isoniazid for treatment of TB if given in conjunction with pyridoxine. Required in patients with CD4 counts \< 200 cells/mm3: * Prophylaxis for PCP. PER AMENDMENT 9/19/96: * After the first 16 weeks of combined IFN alpha-2b and ddI treatment subjects may at the discretion of the investigator receive any FDA approved antiretroviral drug regimen in addition to or in place of ddI. Patients must have: * Positive antibody to HIV. * Biopsy-proven Kaposi's sarcoma (at least 5 measurable lesions, with at least 1 measurable cutaneous lesion) involving the skin, lymph nodes, oral cavity, or asymptomatic lesions of the GI tract not requiring systemic chemotherapy. Lung involvement with Kaposi's sarcoma excludes. * Consent of parent or guardian if less than 18 years of age. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: * Concurrent opportunistic infection or B symptoms including unexplained fever, night sweats, weight loss \> 10 percent, and diarrhea lasting more than 2 weeks. * Visceral (non-nodal) Kaposi's sarcoma requiring cytotoxic chemotherapy. * Severe (\> 2+) tumor-associated edema. * Concurrent neoplasia other than basal cell carcinoma, or anogenital intraepithelial neoplasia. * Current clinical evidence of peripheral neuropathy (= or \> grade 1), pancreatitis, intractable diarrhea, or active seizure disorder not well controlled by anti-seizure medications. * Significant symptomatic cardiac disease. * Medical contraindication. Concurrent Medication: Excluded: * Other investigational, antiviral, immunomodulating, or antitumor agents. * Drugs associated with peripheral neuropathy (other than ddI). PER AMENDMENT 9/19/96: * Other antiretroviral agents may not be taken during the first 16 weeks of combined IFN alpha-2b and ddI treatment. Concurrent Treatment: Excluded: * Radiation therapy. Patients with the following prior conditions are excluded: * Opportunistic infection or B symptoms including unexplained fever, night sweats, weight loss \> 10 percent, and diarrhea lasting more than 2 weeks. * Prior grade 3 or 4 toxicity attributed to ddI therapy. * Prior history of peripheral neuropathy (= or \> grade 1), pancreatitis, intractable diarrhea, or active seizure disorder not well controlled by anti-seizure medications. * History of myocardial infarction or ventricular arrhythmias. Prior Medication: Excluded: * Prior IFN-alpha. * Corticosteroids, biological response modifiers, cytotoxic chemotherapy, or known neurotoxic drugs (other than ddI or ddC) within 30 days prior to study entry. * Therapy with antiretroviral drugs (other than ddI) within 7 days prior to study entry. Prior Treatment: Excluded: * Radiation therapy within 30 days prior to study entry. Risk Behavior: * Alcohol consumption is strongly discouraged. * Patients considered to be noncompliant should be excluded.