ORGANIZING PNEUMONITIS AS A FATAL ADVERSE EFFECT OF TEMOZOLOMIDE: A CASE REPORT AND REVIEW OF THE LITERATURE

Abstract

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Glioblastoma Multiforme is the most aggressive Central Nervous system tumor and has a very poor prognosis in adults.[1] The current treatment regimen includes surgical resection, followed by radiation and Temozolomide.[2] Temozolomide is an oral Alkylating agent approved for the treatment of Glioblastoma Multiforme.[2] It has a very favorable side effect profile and is very well tolerated by most patients.[3] However, in few cases, there are fatal side effects, including organizing pneumonitis, which is characterized by subacute onset of fever, dyspnea, cough, and myalgia, as well as a CT scan finding pulmonary patchy consolidation and ground glass appearance. CASE PRESENTATION: 45- year-old man with a history of Glioblastoma multiforme, treated with tumor resection, radiation, and was started on Temozolomide for the last eight months, who was admitted to ICU for worsening respiratory distress. The Chest X-ray and the CT scan of the chest revealed multifocal interstitial ground-glass consolidations. Infectious causes were ruled out with blood and sputum cultures that were negative and bronchial alveolar lavage (BAL), which was negative for any organisms. The transbronchial biopsy also showed inflammation but no organisms on gram stain or PCR. He was preemptively started on PCP prophylaxis. High-dose steroids were started, for a diagnosis of organizing pneumonitis, with some improvement in radiological findings, but the overall condition deteriorated, with anoxic brain injury, mother changed the code status to control measures, and the patient expired. DISCUSSION: Temozolomide is an oral alkylating agent that has been used in combination with radiation therapy in improving disease progression-free survival in patients with glioblastoma multiforme (1). Multiple adverse effects have been reported in association with the use of temozolomide. Hematologic adverse reactions include thrombocytopenia, lymphopenia, CD4-selective lymphocytopenia with increased risk of opportunistic infections especially pneumocystis jirovecii for PCP prophylaxis treatment should be considered in a patient developing lymphopenia with temozolomide therapy (2). One of the rare but life-threatening idiosyncratic reactions which have been reported in association with temozolomide use is organizing pneumonitis. To our best knowledge, there have been a total of seven cases reported of organizing pneumonia secondary to Temozolomide use, we are summarizing them in table 1. CONCLUSIONS: Organizing pneumonitis is one of the fatal complications that has been reported with the use of temozolomide. Physicians should consider this as one of the differential diagnoses while treating acute respiratory distress in the setting of temozolomide use. Infection should be ruled out and high dose steroid therapy should be started as early as possible and is the key element to achieve medical response and decrease mortality in these patients. REFERENCE #1: 1.Ostrom QT, Gittleman H, Fulop J, et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro-Oncology. 2015;17(suppl 4):iv1-iv62. doi:10.1093/neuonc/nov189 REFERENCE #2: 2.Ostrom QT, Bauchet L, Davis FG, et al. The epidemiology of glioma in adults: a "state of the science" review. Neuro-Oncology. 2014;16(7):896-913. doi:10.1093/neuonc/nou087 REFERENCE #3: 3.Alexander BM, Cloughesy TF. Adult Glioblastoma. Journal of Clinical Oncology. 2017;35(21):2402-2409. doi:10.1200/jco.2017.73.01194.Davis M. Glioblastoma: Overview of Disease and Treatment. Clinical Journal of Oncology Nursing. 2016;20(5):S2-S8. doi:10.1188/16.cjon.s1.2-8 DISCLOSURES: No relevant relationships by Lina Altameemi, source=Web Response No relevant relationships by Jaafar Alward, source=Web Response No relevant relationships by Arul Chandran, source=Web Response No relevant relationships by Harini Lakshman, source=Web Response