the safety and effectiveness of interferon alfa-2b plus didanosine in patients with kaposi's sarcoma

Conditions: Sarcoma, Kaposi; HIV Infections

Summary: 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.

Eligibility criteria:
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.

Keywords: sarcoma, kaposi didanosine drug interactions acquired immunodeficiency syndrome interferon-alpha