MORBIDITY AND TOXIC EFFECTS ASSOCIATED WITH GANCICLOVIR OR FOSCARNET THERAPY IN A RANDOMIZED CYTOMEGALOVIRUS RETINITIS TRIAL

Background: The Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial compared the use of either ganciclovir or foscarnet for the initial tr eatment of cytomegalovirus retinitis in patients with the acquired imm unodeficiency syndrome. We previously reported that patients treated w ith foscarnet lived longer but were more likely to have their treatmen t switched, the latter suggesting foscarnet may not have been as well tolerated as ganciclovir. This study compared the morbidity and toxic reactions reported during the trial. Methods: Two hundred thirty-four patients with the acquired immunodeficiency syndrome and preciously un treated cytomegalovirus retinitis at 11 university centers were random ly assigned to receive intravenously either foscarnet (n = 107) or gan ciclovir (n = 127). Medical histories, laboratory tests, and drug trea tment histories during the first 6 months of treatment were analyzed. Results: Neutropenia was more common in patients assigned to ganciclov ir than to foscarnet (34% vs 14%; P = .001). Patients assigned to fosc arnet reported more infusion-related symptoms (58% vs 24%; P < .001) a nd, in male patients, more genitourinary symptoms (36% vs 16%; P > .00 1); they also experienced a trend toward more nephrotoxic effects (13% vs 6%; P = .082) and electrolyte abnormalities. The incidence of seiz ures was similar in both groups (foscarnet, 12%; ganciclovir, 9%; P = .511). Patients assigned to foscarnet were more likely to be switched to the alternative treatment (foscarnet to ganciclovir, 46%; ganciclov ir to foscarnet, 11%, P < .001), and most of this excess was attributa ble to toxic reactions. In 88% of cases in which treatment was snitche d as a result of toxic reactions and in which follow-up data were avai lable, the toxic reaction resolved after the switch. No permanent disa bility or death resulted from toxic reactions. Conclusions: Compared w ith ganciclovir, the use of foscarnet was more frequently limited by t he occurrence of toxic reactions. However, these toxic reactions rarel y had long-term sequelae. In light of the previously reported survival benefit seen in patients treated with foscarnet, these data support t he use of foscarnet for the initial treatment of cytomegalovirus retin itis.