New antifungal drugs and new clinical trials: Interpreting results may be difficult

Current Opinion in Oncology

Volumn 15, Issue 4, 2003, Pages 283-288

  Girmenia, Corrado ^a   Martino, Pietro ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Caspofungin; Fungal infections; New strategies; Voriconazole

Indexed keywords

AMPHOTERICIN B; AMPHOTERICIN B CHOLESTEROL SULFATE; ANTIFUNGAL AGENT; CASPOFUNGIN; ECHINOCANDIN B; FLUCONAZOLE; MICAFUNGIN; POSACONAZOLE; RAVUCONAZOLE; TRIAZOLE; VORICONAZOLE;

ANTIFUNGAL ACTIVITY; ASPERGILLOSIS; ASPERGILLUS; CANDIDIASIS; CHILL; CLINICAL TRIAL; CREATININE BLOOD LEVEL; DISEASE SEVERITY; DRUG FORMULATION; DRUG POTENTIATION; FEVER; HUMAN; HYPOKALEMIA; IMMUNE DEFICIENCY; INCIDENCE; KIDNEY FAILURE; LIVER TOXICITY; MORTALITY; NAUSEA; NEPHROTOXICITY; PRIORITY JOURNAL; PROGNOSIS; RASH; REVIEW; SIDE EFFECT; STANDARD; VISUAL DISORDER; VISUAL IMPAIRMENT; VOMITING;

ANIMALS; ANTIFUNGAL AGENTS; CLINICAL TRIALS; DATA INTERPRETATION, STATISTICAL; HUMANS; MYCOSES; PEPTIDES; PEPTIDES, CYCLIC; PYRIMIDINES; TRIAZOLES;

EID: 0041737703     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001622-200307000-00001     Document Type: Review

References (24)

1. Maertens J, Van Eldere J, Verhaegen J, et al.: Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis 2002, 186:1297-1306.
2. Herbrecht R, Letscher-Bru V, Oprea C, et al.: Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol 2002, 20:1898-1906.
3. Stevens DA, Kan VL, Judson MA, et al.: Practice guidelines for diseases caused by Aspergillus. Clin Infect Dis 2000, 30:696-709.
4. Bowden R, Chandrasekar P, White MH, et al.: A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis 2002, 35:359-366. This is the first randomized trial in which conventional amphotericin B was compared with a lipid formulation of the drug in the primary therapy of aspergillosis. Respective rates of therapeutic response, mortality, and death caused by fungal infection were similar. Renal toxicity was significantly higher in patients treated with amphotericin B, but infusion-related side effects occurred more frequently in patients treated with ABCD.
5. Herbrecht R, Denning DW, Patterson TF, et al.: Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002, 347:408-415. This is by far the largest prospective controlled study in the treatment of definite or probable invasive aspergillosis. Voriconazole proved to be less toxic, more effective, and associated with a lower mortality rate compared with conventional amphotericin B.
6. Denning DW, Ribaud P, Milpied N, et al.: Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002, 34:563-571.
7. Girmenia C, Cimino G, Micozzi A, et al.: Risk factors for nephrotoxicity associated with conventional amphotericin B therapy. Am J Med 2002, 113:351. In this prospective study on consecutive 46 patients with hematologic malignancies, amphotericin B empiric therapy was administered with adequate hydration and electrolyte supplementation. Only three (7%) patients developed a moderate level of nephrotoxicity that required discontinuation of amphotericin B.
8. Mayer J, Doubek M, Doubek J, et al.: Reduced nephrotoxicity of conventional amphotericin B therapy after minimal nephroprotective measures: animal experiments and clinical study. J Infect Dis 2002, 186:379-388. Animal experiments and a retrospective clinical study showed that adequate hydration and electrolyte supplementation represent simple but effective measures in the containment of amphotericin B-associated renal toxicity.
9. Ernst EJ: Investigational antifungal agents. Pharmacotherapy 2001, 21:165S-174S.
10. Maertens J, Raad I, Petrikkos G, et al. Update of multicenter noncomparative study of caspofungin (CAS) in adults with invasive aspergillosis (IA) refractory (R) or intolerant (I) to other antifungal agents: analysis of 90 patients [abstract M-856]. In: Program and abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (San Diego). Washington, DC: American Society for Microbiology, 2002.
11. Aliff TB, Maslak PG, Jurcic JG, et al.: Refractory aspergillus pneumonia in patients with acute leukaemia: successful therapy with combination caspofungin and liposomal amphotericin B. Cancer 2003, 97:1025-1032.
12. Rex JH, Walsh TJ, Sobel JD, et al.: Practice guidelines for the treatment of candidiasis. Clin Infect Dis 2000, 30:662-678.
13. Edwards JE Jr, Bodey GP, Bowden RA, et al.: International conference for the development of a consensus on the management and prevention of severe candidal infections. Clin Infect Dis 1997, 25:43-59.
14. Ally R, Schurmann D, Kreisel W, et al.: A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis 2001, 33:1447-1454.
15. Villanueva A, Arathoon EG, Gotuzzo E, et al.: A randomized double-blind study of caspofungin versus amphotericin B for the treatment of candidal esophagitis. Clin Infect Dis 2001, 33:1529-1535.
16. Villanueva A, Gotuzzo E, Arathoon EG, et al.: A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Am J Med 2002, 113:294-299.
17. Mora-Duarte J, Betts R, Rotstein C, et al.: Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002, 347:2020-2029. In this double-blind, randomized study, caspofungin and amphotericin B were compared in the treatment of invasive candidiasis. Caspofungin was more effective but less toxic for the treatment of Candida infections, at least in nonneutropenic patients. The mortality rate was similar in the two treatment groups.
18. Johnson LB, Kauffman CA: Voriconazole: a new triazole antifungal agent. Clin Infect Dis 2003, 36:630-637.
19. Paphitou NI, Ostrosky-Zeichner L, Paetznick VL, et al.: In vitro antifungal susceptibilities of Trichosporon species. Antimicrob Agents Chemother 2002, 46:1144-1146.
20. Perfect JR, Marr KA, Walsh TJ, et al.: Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis 2003, 36:1122-1131.
21. Walsh TJ, Lutsar I, Driscoll T, et al.: Voriconazole in the treatment of aspergillosis, scedosporiosis and other fungal infections in children. Pediatr Infect Dis J 2002, 21:240-248.
22. Hughes WT, Armstrong D, Bodey GP, et al.: 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002, 34:730-751
23. Walsh TJ, Pappas P, Winston DJ, et al.: Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002, 346:225-234. In this randomized, international, multicenter trial, voriconazole was compared with liposomal amphotericin B for empirical antifungal therapy. The overall success rate was similar in the two groups, but there were fewer breakthrough fungal infections in the voriconazole group. The voriconazole group had fewer cases of severe infusion-related reactions and of nephrotoxicity.
24. Imhof A, Walter RB, Schaffner A: Continuous infusion of escalated doses of amphotericin B deoxycholate: an open-label observational study. Clin Infect Dis 2003, 36:943-951. Continuous infusion of escalated doses of amphotericin B in 33 patients allowed the administration of 2.0 mg/kg/d of the drug without impairment of vital organ functions and was well tolerated by most patients.