A Phase I evaluation of IFN α-1b in solid tumors, lymphoma or myeloma

Abstract

2550 Background: Interferon alpha 1 (IFN α-1) has been suggested from prior clinical data to be potentially better tolerated than IFN α-2. The objectives of this trial were to confirm the safety, tolerability and maximum dose of recombinant human IFN α-1b and to measure the effects of IFN α-1b on known IFN induced gene products. Methods: Recombinant human IFN α-1b purified to homogeneity (specific activity 1.0 * 108 units/mg on MDBK cells) was obtained from the Ministry of Public Health in Shanghai. Eligible patients had histologically confirmed metastatic malignancy refractory to standard treatments. Patients were sequentially enrolled to receive increasing doses of IFN α-1b administered by SQ injection daily. Patients were monitored weekly and side effects were graded by the NCI common toxicity criteria. Biologic effects of IFN α-1b were assessed by measuring products of the IFN stimulated genes β2-microglobulin, GTP-cyclohydrolase, ISG 15 and TRAIL at baseline and on days 2, 8 and 29. Seven patients enrolled to the first cohort received 15 μg/m2 of IFN α-1b daily. Six patients were enrolled to the second, third and fourth cohorts and received 45, 135 and 270 μg/m2 respectively. Results: Two grade III toxicities (fatigue and headache) occurred in the first cohort. No grade III toxicities were observed in the second and third cohorts. Grade III fever defined DLT in the fourth cohort. No patients experienced significant weight loss or decline in performance status. No grade IV toxicity related to IFN α-1b occurred in any of the cohorts. One patient with metastatic renal cell cancer treated in the highest dose cohort has had a confirmed partial response. Combined analysis demonstrated significant increases compared to baseline at days 2, 8 and 29 for β2-microglobulin and GTP-cyclohydrolase for all four cohorts (p<0.01). ISG 15 increased significantly over baseline in patients receiving the lowest dose while TRAIL showed significant sustained increases in the three higher dose cohorts (p<0.01). Conclusions: IFN α-1b appears well tolerated clinically and demonstrates differential biologic effects. No significant financial relationships to disclose.