Abstract
Invasive fungal infections (IFIs) are serious complications in elderly adults. Caspofungin may provide a useful therapeutic option for elderly patients with or at high risk for IFIs. We retrospectively compared efficacy and safety outcomes in elderly (≥65 years of age) and non-elderly patients in three clinical trials of caspofungin: a double-blind, randomized trial versus amphotericin B for documented invasive candidiasis (IC); an open-label, non-comparative study of definite or probable invasive aspergillosis (IA); and a double-blind, randomized trial versus liposomal amphotericin B as empirical therapy (ET) in febrile neutropenic patients. A total of 159 elderly patients with a median age of 71 years (range, 65–84) received caspofungin in these studies. The median duration of caspofungin therapy was 12 days for IC and ET, and 28 days for IA. Point estimates for the favorable response rates to caspofungin were numerically higher in elderly versus non-elderly patients with IC (83% vs. 68%) or IA (64% vs. 44%) and were similar in patients receiving ET (36% vs. 34%). Adverse events related to caspofungin occurred in generally similar proportions of elderly versus non-elderly patients with IC (clinical, 33% vs. 27%; laboratory, 17% vs. 29%), with IA (clinical, 7% vs. 13%; laboratory, 13% vs. 14%), or receiving ET (clinical, 47% vs. 47%; laboratory, 24% vs. 22%). Nephrotoxicity and infusion-related toxicity developed in comparable proportions of elderly and non-elderly caspofungin recipients in all three studies. In this post-hoc analysis, caspofungin appeared to be as efficacious and well tolerated in elderly patients as in non-elderly patients.
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References
Hedderwick S, Kauffman CA (1997) Opportunistic fungal infections: superficial and systemic candidiasis. Geriatrics 52:50–59
Fridkin SK, Jarvis WR (1996) Epidemiology of nosocomial fungal infections. Clin Microbiol Rev 9:499–511
Wey SB, Mori M, Pfaller MA, et al (1989) Risk factors for hospital-acquired candidemia. Arch Intern Med 149:2349–2353
Nucci M, Colombo AL, Silveira F, et al (1998) Risk factors for death in patients with candidemia. Infect Control Hosp Epidemiol 19:846–850
Kauffman CA, Hedderwick SA (2001) Treatment of systemic fungal infections in older patients: achieving optimal outcomes. Drugs Aging 18:313–323
Lin SJ, Schrantz J, Teutsch SM (2001) Aspergillosis case-fatality rate: systemic review of the literature. Clin Infect Dis 32:358–366
Bressler R, Bahl JJ (2003) Principles of drug therapy for the elderly patient. Mayo Clin Proc 78:1564–1577
Faulkner CM, Cox HL, Williamson JC (2005) Unique aspects of antimicrobial use in older adults. Clin Infect Dis 40:997–1004
Kauffman CA, Carver PL (1997) Use of azoles for systemic antifungal therapy. Adv Pharmacol 39:143–189
Dismukes WE (2000) Introduction to antifungal drugs. Clin Infect Dis 30:653–657
Stone JA, Ballow CH, Holland SD, et al (2000) Single dose caspofungin pharmacokinetics in healthy elderly subjects. Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy 40:26
Mora-Duarte J, Betts R, Rotstein C, et al (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347:2020–2029
Maertens J, Raad I, Petrikkos G, et al (2004) Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis 39:1563–1571
Walsh TJ, Teppler H, Donowitz GR, et al (2004) Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 351:1391–1402
Cytel Software Corporation (1998) StatXact-4 for windows user manual. Cytel Inc., Cambridge, MA
Assmann SF, Pocock SJ, Enos LE, Kasten LE (2000) Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet 355:1064–1069
Yusuf S, Wittes J, Probstfield J, Tyroler HA (1991) Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA 266:93–98
Lagakos SW (2006) The challenge of subgroup analyses-reporting without distorting. N Engl J Med 354:1667–1669
Author Contributions
The paper was primarily drafted by MDN and KS, and critically reviewed and ultimately approved in essentially final form by all co-authors. Statistical analyses were performed by RL and AM. CS and NK supervised enrollment of subjects and data collection in the three clinical trials included in this analysis. All authors participated in the interpretation of the data and preparation of the manuscript.
Role of Sponsor
These studies were funded by Merck & Co., Inc., which markets caspofungin. Study oversight, data collection and processing, and analysis for each clinical trial were done by Merck Research Laboratories.
Financial Disclosures
All authors were employees of Merck & Co., Inc., during the writing of this manuscript. Current and former Merck employees may own stock and/or stock options in the company.
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This study was sponsored and funded by Merck & Co., Inc. Portions of this report were presented at the 13th European Congress of Clinical Microbology and Infectious Diseases, Glasgow, UK, 10–13 May 2003.
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DiNubile, M.J., Strohmaier, K.M., Lupinacci, R.J. et al. Efficacy and safety of caspofungin therapy in elderly patients with proven or suspected invasive fungal infections. Eur J Clin Microbiol Infect Dis 27, 663–670 (2008). https://doi.org/10.1007/s10096-008-0486-6
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DOI: https://doi.org/10.1007/s10096-008-0486-6