COMPLEMENT ACTIVATION BY PEGYLATED LIPOSOMAL DOXORUBICIN (DOXIL~R) IN CANCER PATIENTS: ASSOCIATION WITH HYPERSENSITIVITY REACTIONS

摘要

To explore the possible role of complement (C) activation in the hypersensitivity reactions (HSR) to liposomal doxorubicin (Doxil) we monitored the formation of C terminal complex (SC5b-9) in cancer patients infused with Doxil. Out of 29 patients evaluated for the presence of HSR 13 displayed moderate to severe reaction. In 8 out of 10 "reactor" patients, evaluated for SC5b-9 changes, plasma SC5b-9 levels at 10 min post-infusion were significantly increased relative to baseline, indicating C activation. In the "non-reactor" group C activation was detected in 50% of patients. In addition to its increased frequency, the extent of C activation, expressed as SC5b-9 peak/baseline ratio, was also significantly greater in the reactor group than in non-reactors. Both the incidence of HSR and the extent of C activation showed positive correlation with the initial rate of Doxil infusion. While providing evidence that Doxil can cause C activation in a high percentage of patients, the present data suggest that such activation plays a causal role in HSR. Nevertheless, the occurrence of C activation in non-reactor patients reveals the involvement of other contributing or rate-limiting factors as well.