Top

International Journal of Clinical Oncology

Published in:

01-11-2019 | Myelodysplastic Syndrome | Original Article

Impact of oral voriconazole during chemotherapy for acute myeloid leukemia and myelodysplastic syndrome: a Japanese nationwide retrospective cohort study

Authors: Ikuyo Tsutsumi, Susumu Kunisawa, Chikashi Yoshida, Masanori Seki, Takuya Komeno, Kiyohide Fushimi, Satoshi Morita, Yuichi Imanaka

Published in: International Journal of Clinical Oncology | Issue 11/2019

Abstract

Background

The prevention of invasive fungal infections is important in patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) receiving cytoreductive chemotherapy. However, the role of oral voriconazole (VRCZ) in such patients has not been established. This study aimed to investigate the effectiveness of oral VRCZ compared to that of first-generation azoles prescribed within 7 days after the onset of chemotherapy in adult patients with AML/MDS using the Japanese administrative database.

Methods

This nationwide retrospective cohort study was conducted using the Diagnosis Procedure Combination/Per-Diem Payment System. The primary outcome was the proportion of patients who switched to intravenous antifungal agents. Analyses using the instrumental variable method were performed to address unmeasured confounding.

Results

In total, data on 5517 inpatients from 142 hospitals were analyzed. An oral VRCZ prescription was significantly associated with a reduction in the proportion of patients switching to intravenous antifungal agents compared to first-generation azole prescription (21.0% (95% confidence interval [CI] − 33.4 to − 8.6)). The impact of oral VRCZ in reducing the proportion of patients switching to intravenous antifungal agents was stronger in patients aged < 65 years than in those aged ≥ 65 years (− 40.6%, 95% CI − 63.2 to − 17.9; − 21.9%, 95% CI − 35.8 to − 8.1, respectively) and in patients prescribed oral azole within 3 days from the onset of chemotherapy than in those prescribed the same later (− 32.9%, 95% CI − 46.7 to − 19.2; − 9.0%, 95% CI − 33.7 to 15.7, respectively).

Conclusion

Oral VRCZ administration may benefit adult patients with AML/MDS undergoing chemotherapy.

Available only for authorised users

Freifeld AG, Bow EJ, Sepkowitz KA et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52:e56–e93. https://doi.org/10.1093/cid/cir073 CrossRefPubMed

Committee for guidelines for deep mycoses (2014) Guidelines for diagnosis and treatment of deep mycoses 2014. Kyowa-kikaku, Tokyo, Japan. ISBN-13: 978-4877941611. Japanese

Cornely OA, Bohme A, Buchheidt D et al (2009) Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica 94:113–122. https://doi.org/10.3324/haematol.11665 CrossRefPubMed

Marks DI, Pagliuca A, Kibbler CC et al (2011) Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation. Br J Haematol 155:318–327. https://doi.org/10.1111/j.1365-2141.2011.08838.x CrossRefPubMedPubMedCentral

Xu SX, Shen JL, Tang XF et al (2016) Newer antifungal agents micafungin and voriconazole for fungal infection prevention during hematopoietic cell transplantation: a meta-analysis. Euro Rev Med Pharmacol Sci 20:381–390

Pechlivanoglou P, Le HH, Daenen S et al (2014) Mixed treatment comparison of prophylaxis against invasive fungal infections in neutropenic patients receiving therapy for haematological malignancies: a systematic review. J Antimicrobial Chemother 69:1–11. https://doi.org/10.1093/jac/dkt329 CrossRef

Riedel A, Choe L, Inciardi J et al (2007) Antifungal prophylaxis in chemotherapy-associated neutropenia: a retrospective, observational study. BMC Infect Dis 7:70. https://doi.org/10.1186/1471-2334-7-70 CrossRefPubMedPubMedCentral

Gergis U, Markey K, Greene J et al (2010) Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD. Bone Marrow Transplant 45:662–667. https://doi.org/10.1038/bmt.2009.210 CrossRefPubMed

Döring M, Blume O, Haufe S et al (2014) Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation. Eur J Clin Microbiol Infect Dis 33:629–638. https://doi.org/10.1007/s10096-013-1998-2 CrossRefPubMed

10.

Winston DJ, Chandrasekar PH, Lazarus HM et al (1993) Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Ann Intern Med 118:495–503CrossRef

11.

Vehreschild JJ, Bohme A, Buchheidt D et al (2007) A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML). J Infect 55:445–449. https://doi.org/10.1016/j.jinf.2007.07.003 CrossRefPubMed

12.

Rotstein C, Bow EJ, Laverdiere M et al (1999) Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. Clin Infect Dis 28:331–340. https://doi.org/10.1086/515128 CrossRefPubMed

13.

Arndt CA, Walsh TJ, McCully CL et al (1988) Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. J Infect Dis 157:178–180CrossRef

14.

Girmenia C (2009) New generation azole antifungals in clinical investigation. Expert Opin Investig Drugs 18:1279–1295. https://doi.org/10.1517/13543780903176407 CrossRefPubMed

15.

Kale P, Johnson LB (2005) Second-generation azole antifungal agents. Drugs Ttoday (Barc) 41:91–105. https://doi.org/10.1358/dot.2005.41.2.882661 CrossRef

16.

Jørgensen KJ, Gøtzsche PC, Dalbøge CS et al (2014) Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia. Cochrane Database Syst Rev Issue 2:4707. https://doi.org/10.1002/14651858.CD004707.pub3 CrossRef

17.

Ministry of Health, Labour and Welfare. Research on evaluation and impact of DPC introduction: aggregate results. https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000049343.html. Accessed 05 Mar 2019

18.

Cameron AC, Trivedi PK (2010) Microeconometrics using stata: revised Edition, 2nd edn. Stata Press, College Station, Texas

19.

Brookhart MA, Wang PS, Solomon DH et al (2006) Evaluating short-term drug effects using a physician-specific prescribing preference as an instrumental variable. Epidemiology (Camb) 17:268–275. https://doi.org/10.1097/01.ede.0000193606.58671.c5 CrossRef

20.

Martens EP, Pestman WR, de Boer A et al (2006) Instrumental variables: application and limitations. Epidemiology 17(3):260–267. https://doi.org/10.1097/01.ede.0000215160.88317.cb CrossRefPubMed

21.

Fitzmaurice GM, Laird NM, Ware JH (2011) Applied longitudinal analysis, 2nd edn. Wiley, Hoboken, NJCrossRef

22.

Maciejewski ML, Brookhart MA (2019) Using instrumental variables to address bias from unobserved confounders. JAMA 321(21):2124–2125. https://doi.org/10.1001/jama.2019.5646 CrossRefPubMed

23.

Baltagi BH (2013) Econometric analysis of panel data, 5th edn. Wiley, Chichester, West Sussex

24.

Davies NM, Gunnell D, Thomas KH et al (2013) Physicians' prescribing preferences were a potential instrument for patients' actual prescriptions of antidepressants. J Clin Epidemiol 66:1386–1396. https://doi.org/10.1016/j.jclinepi.2013.06.008 CrossRefPubMedPubMedCentral

25.

Uddin MJ, Groenwold RHH, de Boer A et al (2016) Evaluating different physician's prescribing preference based instrumental variables in two primary care databases: a study of inhaled long-acting beta2-agonist use and the risk of myocardial infarction. Pharmacoepidemiol Drug Saf 25(Suppl 1):132–141. https://doi.org/10.1002/pds.3860 CrossRefPubMed

26.

Shah A, Ganesan P, Radhakrishnan V et al (2016) Voriconazole is a safe and effective anti-fungal prophylactic agent during induction therapy of acute myeloid leukemia. Indian J Med Paediatr Oncol 37:53–58. https://doi.org/10.4103/0971-5851.177032 CrossRefPubMedPubMedCentral

27.

Ping B, Zhu Y, Gao Y et al (2013) Second- versus first-generation azoles for antifungal prophylaxis in hematology patients: a systematic review and meta-analysis. Ann Hematol 92:831–839. https://doi.org/10.1007/s00277-013-1693-5 CrossRefPubMed

28.

Wingard JR, Carter SL, Walsh TJ et al (2010) Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood 116:5111–5118. https://doi.org/10.1182/blood-2010-02-268151 CrossRefPubMedPubMedCentral

29.

Ananda-Rajah MR, Grigg A, Downey MT et al (2012) Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period. Haematologica 97:459–463. https://doi.org/10.3324/haematol.2011.051995 CrossRefPubMedPubMedCentral

30.

Mattiuzzi GN, Cortes J, Alvarado G et al (2011) Efficacy and safety of intravenous voriconazole and intravenous itraconazole for antifungal prophylaxis in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome. Support Care Cancer 19:19–26. https://doi.org/10.1007/s00520-009-0783-3 CrossRefPubMed

31.

Brookhart MA, Stürmer T, Glynn RJ et al (2010) Confounding control in healthcare database research: challenges and potential approaches. Med Care 48:S114–S120. https://doi.org/10.1097/MLR.0b013e3181dbebe3 CrossRefPubMedPubMedCentral

32.

Kimura S, Fujita H, Kato H et al (2017) Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group. Support Care Cancer 25:3515–3521. https://doi.org/10.1007/s00520-017-3775-8 CrossRefPubMed

Title: Impact of oral voriconazole during chemotherapy for acute myeloid leukemia and myelodysplastic syndrome: a Japanese nationwide retrospective cohort study
Authors: Ikuyo Tsutsumi
Susumu Kunisawa
Chikashi Yoshida
Masanori Seki
Takuya Komeno
Kiyohide Fushimi
Satoshi Morita
Yuichi Imanaka
Publication date: 01-11-2019
Publisher: Springer Singapore
Keywords: Myelodysplastic Syndrome
Acute Myeloid Leukemia
Itraconazole
Fluconazole
Voriconazole
Cytostatic Therapy
Published in: International Journal of Clinical Oncology / Issue 11/2019
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-019-01506-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2019

The evolution of surgical treatment for gastrointestinal cancers

Neoadjuvant chemotherapy followed by radical hysterectomy for stage IB2-to-IIB cervical cancer: a retrospective cohort study

Including positive lymph node count in the AJCC N staging may be a better predictor of the prognosis of NSCLC patients, especially stage III patients: a large population-based study

Efficacy of chemotherapy for older patients with gastric cancer: a multicenter retrospective cohort study

Development and validation of a nomogram containing the prognostic determinants of chondrosarcoma based on the Surveillance, Epidemiology, and End Results database

Analysis of response-related endpoints in trials of first-line medical treatment of metastatic colorectal cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer