Dan Longo

Human lymphoblastoid interferon treatment of Kaposi's sarcoma in the acquired immune deficiency syndrome. Clinical response and prognostic parameters

Thirty consecutive patients with the acquired immune deficiency syndrome were treated with intramuscular human lymphoblastoid interferon for Kaposis sarcoma. Patients were divided into three groups receiving 7.5 million units/m2 per day, 15 million units/m2 per day, or 25 million units/m2 per day for 28 days. Because of dose-limiting toxicity in the highest dose group, all patients received between 6 and 15 million units/m2 per day. There were three partial responses and four minor responses. The responses were not dependent on drug dose, but did correlate with higher total lymphocyte and OKT4-positive lymphocyte numbers and absence of prior opportunistic infection. Patients who had endogenous acid-labile alpha-interferon prior to therapy were more likely to have progressive disease during interferon administration.

Combination chemotherapy of disseminated kaposi's sarcoma in patients with the acquired immune deficiency syndrome

Two clinical trials were conducted to assess the efficacy and safety of a combination chemotherapy regimen for the treatment of Kaposis sarcoma in patients with the acquired immune deficiency syndrome (AIDS). Eighteen consecutive patients with disseminated Kaposis sarcoma were treated with a six-drug regimen of doxorubicin (Adriamycin), vinblastine, bleomycin/actinomycin D, vincristine, dacarbazine (ABV/ADV). A brief partial or complete response was achieved in 13 patients. Most patients died of opportunistic infections. Eighteen consecutive patients with disseminated Kaposis sarcoma were then randomly assigned to therapy with either recombinant alpha interferon or ABV/ADV. The treatment responses in these two groups were comparable to results of earlier trials, and the incidence of opportunistic infections during therapy did not differ between the two treatment arms. It is concluded that chemotherapy is effective and safe for use in palliative management of Kaposis sarcoma in patients with AIDS.

Phase I evaluation of recombinant tumor necrosis factor given in combination with recombinant interferon-gamma

Summary: In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.) injection of IFN-γ, followed 5 min later by an i.m. injection of TNF-α, each agent in different sites, every other day for ten doses over 20 days. Patients received 10, 50, or 100 μ/m2 of each agent throughout the treatment course. No dose modifications were made. Patients suffering serious toxicity had therapy stopped and were considered to be offstudy. All patients experienced fatigue, and 36% spent over half their time in bed on treatment days. Fever and chills were nearly universal. Mild to moderate elevations in serum transaminase levels were noted in 44% of patients, and 44% developed transient microscopic hematuria. Although 81% of patients had anorexia, only 17% of patients lost more than 3 kg of body wt during the 3 weeks of therapy. Because two of three patients receiving 100 μ g/m2 of both agents developed serious toxicity (one fever <105°F, one thrombocytopenia 43,000/mm3), the MTD was established to be 100 μ g/m2 of IFN-γ plus 50 μg /m2 of TNF-α. The use of aspirin did not significantly alter the toxic effects of the agents. One patient with melanoma had a mixed response and one patient with mesothelioma transiently cleared his ascites of malignant cells.