Caution Advised Using Combination Ketoconazole and PD-1 Inhibitors
ABSTRACT: Objective: Immune checkpoint inhibitors are approved to treat multiple cancers. We report life-threatening hepatic failure in 2 consecutive patients with Cushing syndrome that were treated with ketoconazole (KTZ) in combination with 2 different programmed cell death protein 1 (PD-1) inhib...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | AACE Clinical Case Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2376060520306179 |
| _version_ | 1818948166711508992 |
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| author | Yingying Yang Joel R. Hecht Sandy Ting Liu Melissa J. Cohen Steven D. Hart Hanlin L. Wang Anthony P. Heaney |
| author_facet | Yingying Yang Joel R. Hecht Sandy Ting Liu Melissa J. Cohen Steven D. Hart Hanlin L. Wang Anthony P. Heaney |
| author_sort | Yingying Yang |
| collection | DOAJ |
| description | ABSTRACT: Objective: Immune checkpoint inhibitors are approved to treat multiple cancers. We report life-threatening hepatic failure in 2 consecutive patients with Cushing syndrome that were treated with ketoconazole (KTZ) in combination with 2 different programmed cell death protein 1 (PD-1) inhibitors, Nivolumab and Pembrolizumab. Methods: The first patient suffered from corticotroph pituitary carcinoma and the second from metastatic adrenal cortical carcinoma. They were both treated with KTZ for tumor-associated hypercortisolism. Results: Hepatic function was normal on KTZ prior to initiation of PD-1 inhibitors, after which they rapidly developed severe hepatic dysfunction. In both cases, liver biopsy was consistent with drug-induced hepatic injury. Liver function fully recovered on discontinuing KTZ and the PD-1 inhibitors along with methylprednisone therapy. Conclusion: Antifungal azole therapy is commonly used in oncology patients who may be co-treated with PD-1 inhibitors. Although the specific combination of KTZ and PD-1 inhibitors to treat Cushing syndrome may be relatively uncommon, we recommend careful monitoring of hepatic function using a combination PD-1 inhibitors and azole antifungal agents, especially KTZ, due to the potential of life-threatening hepatic failure. Abbreviations: ACTH adrenocorticotropic hormone CS Cushing syndrome ICI immune checkpoint inhibitor KTZ ketoconazole MRI magnetic resonance imaging PD-1 programmed cell death protein 1 |
| first_indexed | 2024-12-20T08:42:29Z |
| format | Article |
| id | doaj.art-c5fcc872bf2f48bda64b3a1257268629 |
| institution | Directory Open Access Journal |
| issn | 2376-0605 |
| language | English |
| last_indexed | 2024-12-20T08:42:29Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | AACE Clinical Case Reports |
| spelling | doaj.art-c5fcc872bf2f48bda64b3a12572686292022-12-21T19:46:21ZengElsevierAACE Clinical Case Reports2376-06052020-09-0165e239e242Caution Advised Using Combination Ketoconazole and PD-1 InhibitorsYingying Yang0Joel R. Hecht1Sandy Ting Liu2Melissa J. Cohen3Steven D. Hart4Hanlin L. Wang5Anthony P. Heaney6From the Divisions of Endocrinology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California.Hematology and Oncology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California.From the Divisions of Endocrinology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California.From the Divisions of Endocrinology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California.the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California.the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California.From the Divisions of Endocrinology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California.; Address correspondence to Anthony P. Heaney, 200 UCLA Medical Plaza, CA 90095.ABSTRACT: Objective: Immune checkpoint inhibitors are approved to treat multiple cancers. We report life-threatening hepatic failure in 2 consecutive patients with Cushing syndrome that were treated with ketoconazole (KTZ) in combination with 2 different programmed cell death protein 1 (PD-1) inhibitors, Nivolumab and Pembrolizumab. Methods: The first patient suffered from corticotroph pituitary carcinoma and the second from metastatic adrenal cortical carcinoma. They were both treated with KTZ for tumor-associated hypercortisolism. Results: Hepatic function was normal on KTZ prior to initiation of PD-1 inhibitors, after which they rapidly developed severe hepatic dysfunction. In both cases, liver biopsy was consistent with drug-induced hepatic injury. Liver function fully recovered on discontinuing KTZ and the PD-1 inhibitors along with methylprednisone therapy. Conclusion: Antifungal azole therapy is commonly used in oncology patients who may be co-treated with PD-1 inhibitors. Although the specific combination of KTZ and PD-1 inhibitors to treat Cushing syndrome may be relatively uncommon, we recommend careful monitoring of hepatic function using a combination PD-1 inhibitors and azole antifungal agents, especially KTZ, due to the potential of life-threatening hepatic failure. Abbreviations: ACTH adrenocorticotropic hormone CS Cushing syndrome ICI immune checkpoint inhibitor KTZ ketoconazole MRI magnetic resonance imaging PD-1 programmed cell death protein 1http://www.sciencedirect.com/science/article/pii/S2376060520306179 |
| spellingShingle | Yingying Yang Joel R. Hecht Sandy Ting Liu Melissa J. Cohen Steven D. Hart Hanlin L. Wang Anthony P. Heaney Caution Advised Using Combination Ketoconazole and PD-1 Inhibitors AACE Clinical Case Reports |
| title | Caution Advised Using Combination Ketoconazole and PD-1 Inhibitors |
| title_full | Caution Advised Using Combination Ketoconazole and PD-1 Inhibitors |
| title_fullStr | Caution Advised Using Combination Ketoconazole and PD-1 Inhibitors |
| title_full_unstemmed | Caution Advised Using Combination Ketoconazole and PD-1 Inhibitors |
| title_short | Caution Advised Using Combination Ketoconazole and PD-1 Inhibitors |
| title_sort | caution advised using combination ketoconazole and pd 1 inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S2376060520306179 |
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