Interferons in the treatment of XXXX .

@entity1 @entity5 @entity229 @entity786 @entity3601 @entity1582 @entity1778
Recently, recombinant DNA methods have been successfully applied to interferon production, making adequate quantities available for both in vitro and in vivo testing. Although interferons are in the class of biologic response modifiers, they do have some direct cytotoxic effects on @entity1 @entity5 cells that can be quantitated in vitro with the colony-forming assay. In the clonogenic assay, RPMI-8226 @entity1582 cells were tested with interferon alfa-2b (Intron A, Schering Corp., Kenilworth, NJ), @entity3601 , @entity786 , and @entity229 . With concentrations of interferon alfa-2b as low as 1 U/ml (international antiviral activity), colony number was reduced to less than 30% of the untreated control cultures. Both @entity3601 and @entity786 showed measurable cytotoxic activity, with the ID50 of @entity3601 at 0.15 microgram/ml and that of @entity786 at 0.4 microgram/ml. @entity229 had the least cytotoxic effect when tested with these @entity1582 cells as a single agent. Additive antiproliferative effects were noted with combinations of interferon alfa-2b plus @entity786 and interferon alfa-2b plus @entity229 . However, the interferon- @entity3601 combination showed synergistic effects on @entity5 colony cell reduction. Even greater cytotoxic activity was seen with the three-drug combination of interferon alfa-2b, @entity3601 , and @entity229 . Clinical trials have shown that interferon alfa-2b may be effective in relapsing and refractory @entity1 with @entity1582 . Of 38 evaluable @entity1 , a total of seven responded to treatment; one @entity1 had a complete response, and six had a partial response. Three of the seven responders have continued to respond for over 33 months, with monoclonal proteins approaching undetectable levels. A pilot study of the feasibility of combining interferon alfa-2b with @entity3601 and @entity229 in previously untreated @entity1 with @entity1582 has been completed. It is concluded that interferon alfa-2b, in dosages not exceeding 2.0 X 10(6) IU/m2, can be safely given in combination with @entity3601 and @entity229 , without compromising @entity3601 dosage. Although response was not the primary objective of the study, an overall response of 75% was achieved using the criteria established by the @entity1778 Task Force.
