Phase I study of recombinant beta-interferon given by four-hour infusion.

Twelve patients with advanced malignant disease were entered onto a Phase I study of escalating doses of beta-interferon serine given by 4-h i.v. infusion twice a wk. Three patients each were entered at starting doses of 0.01, 1, 10, and 30 million units (MU)/m2. Doses escalation within individual patients was allowed to a maximum dose of 400 MU/m2. Fever, chills, fatigue, and acral cyanosis were commonly seen and increased in frequency at higher doses. Myalgia, nausea, diarrhea, headache, and confusion were seen at lesser frequencies. Mild leukopenia, paresthesia, infusion site erythema, and hypotension were each seen in one patient. No conventional maximal tolerated dose could be defined, since several patients underwent escalation to the highest allowable dose and seemed to develop tolerance to acute toxicities. However, a maximal starting dose of 10 MU/m2 was identified, such that those begun at this level or below tolerated semiweekly dose escalation, while those begun at 30 MU/m2 could not tolerate continued therapy. Detectable serum interferon levels were noted during treatment at 10 and 30 MU/m2, the levels at which significant toxicity also first appeared. A maximal starting dose of 10 MU/m2, with gradual escalation as tolerance to side effects develops, is suggested if therapy with high-dose beta-interferon serine is given by 4-h infusion.