TY - JOUR
T1 - Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy
T2 - An externally controlled trial
AU - Walsh, Thomas J.
AU - Raad, Issam
AU - Patterson, Thomas F.
AU - Chandrasekar, Pranatharthi
AU - Donowitz, Gerald R.
AU - Graybill, Richard
AU - Greene, Reginald E.
AU - Hachem, Ray
AU - Hadley, Susan
AU - Herbrecht, Raoul
AU - Langston, Amelia
AU - Louie, Arnold
AU - Ribaud, Patricia
AU - Segal, Brahm H.
AU - Stevens, David A.
AU - Van Burik, Jo Anne H.
AU - White, Charles S.
AU - Corcoran, Gavin
AU - Gogate, Jagadish
AU - Krishna, Gopal
AU - Pedicone, Lisa
AU - Hardalo, Catherine
AU - Perfect, John R.
N1 - Funding Information:
Potential conflicts of interest. I.R. has received research funding from Schering-Plough and Wyeth-Ayerst; serves on the speakers’ bureau for Astellas, Merck, Pfizer, and Wyeth-Ayerst; and is a consultant to Peninsula and Vicuron. T.F.P. has received grant support from Astellas Pharma US, Enzon, Merck, Pfizer, and Schering-Plough; serves on the speakers’ bureau for Astellas Pharma US, Merck, Pfizer, and Schering-Plough; and serves as a consultant to Affinium, Astellas, Basilea, Diversa, Eisai, MediciNova, Merck, Microbia, Nektar Therapeutics, Pfizer, Rib-X, Schering-Plough, and J. Uriach & Cía. P.C. serves on the speakers’ bureau for Merck, Pfizer, and Schering-Plough and serves as a consultant to Enzon. G.R.D. has taken part in studies for Enzon, Fujisawa, and Merck. R.G. is a member of the advisory board for Indevus, Merck, Pfizer, and Schering-Plough; has received research support from Astellas, Indevus, Merck, Pfizer, and Schering-Plough; serves on the speakers’ bureau for Merck (continuing medical education [CME] meetings only); and occasionally speaks at CME events for Pfizer. R.E.G. serves on the speakers’ bureau at Pfizer. R.H. has received research funding from Enzon, Merck, and Pfizer and serves as a consultant to Schering-Plough, Vicuron, and Pfizer. S.H. has received research funding from Astellas (formerly Fujisawa), Enzon (formerly Liposome), Ortho Biotech, Pfizer, and Schering-Plough; serves as a consultant to Enzon, Merck, and Schering-Plough; and serves on the speakers’ bureau for Astellas, Merck, and Pfizer. R.H. has received research support from Pfizer and has served as a consultant to or been a member of the speakers’ bureau for ACE Biosciences, Gilead Sciences, Merck Sharp & Dohme, Pfizer, Schering-Plough, and Zeneus. A.L. is a consultant for Schering-Plough. A.L. has received research support from Merck and Pfizer. P.R. is a member of the speaker’s bureau for Pfizer and Merck. B.H.S. has received compensation from Schering-Plough for serving as a member of the data review committee for this study, has received laboratory support from Enzon, and has received speaking honoraria from Merck and Pfizer. D.A.S. has received grant support from and is a consultant to Schering-Plough. J.-A.H.V.B. has served as a consultant to Pfizer and Schering-Plough; has received clinical trial research support from Astellas, Enzon, Merck, and Schering-Plough; and serves on the speakers’ bureau for Astellas. G.C. was an employee of Schering-Plough Research Institute at the time that this study was conducted; he is currently employed by Stiefel Laboratories (Coral Gables, FL). J.G. was an employee of Schering-Plough Research Institute at the time that this study was conducted; he is currently employed by Eisai (Rahway, NJ). G.K., L.P., and C.H. are employees of Schering-Plough Research Institute. J.R.P has received research support and honoraria from and is a consultant to Schering-Plough. T.J.W. and C.S.W.: no conflicts.
PY - 2007/1/1
Y1 - 2007/1/1
N2 - Background. Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. Methods. We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. Results. Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P = .006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. Conclusions. Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.
AB - Background. Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. Methods. We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. Results. Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P = .006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. Conclusions. Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.
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U2 - 10.1086/508774
DO - 10.1086/508774
M3 - Article
C2 - 17143808
AN - SCOPUS:33845710284
SN - 1058-4838
VL - 44
SP - 2
EP - 12
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -