January 9, 1995

Morbidity and Toxic Effects Associated With Ganciclovir or Foscarnet Therapy in a Randomized Cytomegalovirus Retinitis Trial

Richard A. Lewis, MD, MS; Pamela Clogston, COT; Victor Fainstein, MD; et al Ronald Gross, MD; Tobias Samo, MD; Colette Tuttle, RN; Douglas A. Jabs, MD; Linda Apuzzo; John Bartlett, MD; Laura Coleson, RN, MPH; J. P. Dunn, MD; Lois Eldred, PA-C; Judith Feinberg, MD; Thomas Flynn, MD; Rosemary King, PA-C; Jo Leslie, PA-C; Bruce Barron, MD; Deborah Greenspan, RN; Cynthia Le-Count; Gholam Peyman, MD; Rudolph Franklin, MD; Murk-Hein Heinemann, MD; Bruce Polsky, MD; Kathleen Squires, MD; Susanne Wise-Campbell, RN; Alan H. Friedman, MD; Tony W. Cheung, MD; Norma Justin, MS; Steven Teich, MD; Henry Sacks, MD, PhD; Colette Severin, MS; Dorothy N. Friedberg, MD, PhD; Adrienne Addessi, MA, RN; Douglas Dieterich, MD; Kevin Frost; David Weinberg, MD; Lee Jampol, MD; Robert Murphy, MD; Kathleen Naughton, RN; Dale Henderly, MD; Gary N. Holland, MD; Suzette Chafey, RN, NP; Holly Fall, RN, MN, NP; W. David Hardy, MD; Chris Kimbrell, RN; Lesley J. MacArthur, MA; William R. Freeman, MD; Linda Meixnert, RN; Timothy J. Peterson, MD; Jose I. Quiceno, MD; Leland Rickman, MD; Mary Ann Simanello, RN; Stephen Spector, MD; James O'Donnell, MD; Jacqueline Hoffman; Alexander Irvine, MD; Mark Jacobson, MD; James Larson, COT; Stuart Seiff, MD; Maxine Wanner; Janet Davis, MD; Elaine Chuang, MD; Millie Espinal; Paul Mendez, MD; Ruth Vandenbroucke; Sarah H. Cheeseman, MD; John Gittinger, MD; Richard Haubrich, MD; Harry Kachadoorian, CRA; Karen Tolson; Joan M. Kline; Amy C. Klemm; Maria Stevens; Rene Webb; Jude Brown-Bellamy, MAS; Jan A. Markowitz, PhD; Curtis L. Meinert, PhD; Karen L. Binder; Ronald Brookmeyer, PhD; Vivian E. Brown; Betty J. Collison; John Dodge; Michele Donithan, MHS; Nancy Fink, MPH; Charlotte Gerczak, MLA; Janet T. Holbrook, MS, MPH; Milana R. Isaacson; Camara P. Jones, MD, MPH; Charlene R. Levine; Yuan-I Min, MPH; J. L. Meinert; Rosetta M. Owens; Deborah J. Nowakowski; A. Saah; Gordon R. Sandford, MD; Stephen Singer; Michael Smith; Alice L. Sternberg, ScM; James Tonascia, PhD; Mark L. Van Natta, MHS; Matthew D. Davis, MD; Maria Agres-Segal; Jane Armstrong; Rosemary Brothers; Ginger Freitag; Larry Hubbard, MAT; Dolores Hurlburt; Linda Kastorff; Yvonne Magli; Kathleen Miner; Suzanne Thomas; Marilyn Vanderhoof-Young; Gary Stewart, MS, RPh; Robert Hughes; Lisa Welch, RPh, MAS; Richard Mowery, PhD; Susan Ellenberg, PhD; Joyce Korvick, MD; Tom Clark, CRA; Pamela S. Clogston; William Freeman, MD; Larry Hubbard, MA; Fred Sattler, MD; Colin Jordan, MD; John Mills, MD; Byron W. Brown Jr, PhD; Brian Conway, MD; James Grizzle, PhD; Robert Nussenblatt, MD; John Phair, MD; Harmon Smith, PhD
Author Affiliations

Baylor College of Medicine, Cullen Eye Institute, Houston, Tex; The Johns Hopkins University School of Medicine, Baltimore, Md; Louisiana State University Medical Center, New Orleans; Memorial Sloan-Kettering Cancer Center; New York Hospital; Cornell Medical Center, New York; Mount Sinai School of Medicine, New York, NY; New York University Medical Center, New York; Northwestern University, Chicago, Ill; University of California— Los Angeles; University of California—San Diego; University of California—San Francisco; University of Miami (Fla) School of Medicine; University of Massachusetts Medical Center, Worcester; Chairman's Office, The Johns Hopkins University School of Medicine, Baltimore, Md; Coordinating Center, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Md; Fundus Photograph Reading Center, University of Wisconsin, Madison; Drug Distribution Center, ERC Bioservices Corporation, Rockville, Md; National Eye Institute, Bethesda, Md; National Institute of Allergy and Infectious Diseases, Bethesda, Md; SOCA-ACTG Joint Executive Committee; Policy and Data Monitoring Board

Arch Intern Med. 1995;155(1):65-74. doi:10.1001/archinte.1995.00430010071010

Background:  The Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial compared the use of either ganciclovir or foscarnet for the initial treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. We previously reported that patients treated with foscarnet lived longer but were more likely to have their treatment 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 previously untreated cytomegalovirus retinitis at 11 university centers were randomly assigned to receive intravenously either foscarnet (n=107) or ganciclovir (n=127). Medical histories, laboratory tests, and drug treatment histories during the first 6 months of treatment were analyzed.

Results:  Neutropenia was more common in patients assigned to ganciclovir than to foscarnet (34% vs 14%; P=.001). Patients assigned to foscarnet reported more infusion-related symptoms (58% vs 24%; P<.001) and, in male patients, more genitourinary symptoms (36% vs 16%; P>.001); they also experienced a trend toward more nephrotoxic effects (13% vs 6%; P=.082) and electrolyte abnormalities. The incidence of seizures 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%; ganciclovir to foscarnet, 11%; P<.001), and most of this excess was attributable to toxic reactions. In 88% of cases in which treatment was switched as a result of toxic reactions and in which follow-up data were available, the toxic reaction resolved after the switch. No permanent disability or death resulted from toxic reactions.

Conclusions:  Compared with ganciclovir, the use of foscarnet was more frequently limited by the occurrence of toxic reactions. However, these toxic reactions rarely had long-term sequelae. In light of the previously reported survival benefit seen in patients treated with foscarnet, these data support the use of foscarnet for the initial treatment of cytomegalovirus retinitis.(Arch Intern Med. 1995;155:65-74)