PHASE-II DOSE-RANGING TRIAL OF FOSCARNET SALVAGE THERAPY FOR CYTOMEGALOVIRUS RETINITIS IN AIDS PATIENTS INTOLERANT OF OR RESISTANT TO GANCICLOVIR (ACTG PROTOCOL 093)

Objective: To document response to foscarnet salvage therapy in patien ts with cytomegalovirus (CMV) retinitis who are intolerant of or resis tant to ganciclovir. Methods: Patients with AIDS and CMV retinitis who had documented hematologic intolerance or resistance to ganciclovir t herapy received an induction course of foscarnet, 60 mg/kg every 8h fo r 14 days, and subsequent chronic maintenance foscarnet therapy at a d aily dose of 60, 90 or 120 mg/kg/day. The first 87 patients were rando mly assigned to receive maintenance foscarnet at a dose of 60 or 90 mg /kg/day; all subsequent patients were assigned a maintenance dose of 1 20 mg/kg/day. Results: A total of 156 evaluable patients were enrolled . Median time to retinitis progression and survival did not differ sig nificantly among groups assigned to different maintenance foscarnet do ses. Among patients with retinitis progression documented ophthalmolog ically occuring at less-than-or-equal-to 2 week intervals, despite opt imal doses of ganciclovir, time to progression on foscarnet therapy wa s a median 8 weeks at all doses studied. By dose assignment, there wer e no significant differences in serious drug-associated toxicity, alth ough trends toward increased renal and hypocalcemic adverse events wer e observed at higher maintenance doses. Conclusion: in patients intole rant of ganciclovir, salvage foscarnet therapy resulted in a longer ti me to retinitis progression than reported previously in historic contr ols who terminated ganciclovir therapy. In patients who exhibited clin ical resistance to ganciclovir, foscarnet appeared to have efficacy in controlling retinitis. No significant differences in either efficacy or toxicity were observed in the range of foscarnet maintenance doses studied.