A RARE CASE OF OXALIPLATIN-INDUCED PULMONARY FIBROSIS

Abstract

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Oxaliplatin is a third generation platinum derivative alkylating agent. The platinum compound binds to the DNA forming crosslink which inhibits DNA replication and transcription, resulting in cell death. It is a nonspecific cell cycle cytotoxic agent. Common side effects are peripheral neuropathy, and induced hypersensitivity [1]. CASE PRESENTATION: 65-year-old Caucasian male with past medical history of chronic obstructive pulmonary disease not on home oxygen, former tobacco smoker and alcohol user presents to the emergency department for worsening dyspnea for three weeks. He recently completed 6 cycles of 5 Fluorouracil and Oxaliplatin for Stage IIIA Sigmoid Adenocarcinoma. Patient denies use of recreational drugs. Earlier that day he was at the pulmonary clinic and ambulatory oxygen measurement showed saturation of 60% on room air. High dose steriods were initiated, the patient continued to require high flow nasal cannula and then was on noninvasive positive pressure ventilation. He was subsequently intubated and his course was complicated by a left pneumothorax requiring a chest tube. He was not a candidate for a lung transplant and was placed on comfort care and expired shortly thereafter. Review of system: positive for cough, white phlegm, chills for three days. Physical Exam: afebrile, heart rate 108, respiration 30-34, blood pressure 142/91, oxygen saturation 89% on high flow nasal cannula of 40 liters per minute, and fraction of inspired oxygen of 100%. He appeared acutely ill, unable to complete full sentences, alert and oriented x4. Lungs had bilateral crackles and expiratory wheezes. Diagnostic: Leukocytosis 14.7, Hgb/Hct:11.0/ 34.6. platelet 143. ALT 59, AST 78, AlkPhos 164, LDH 1,333. CRP 4.79, negative troponin, TSH 0.2446, Procalcitonin 0.2. Negative Mycoplasma, and Covid PCR times two. ABG shows respiratory alkalosis. Sputum and blood cultures are negative. CT chest with contrast at another hospital showed subpleural fibrotic changes within lungs bilaterally. CT Angiogram 8 days later showed extensive bullous disease throughout both lungs with areas of emphysematous changes, moderate to severe interstitial changes along the periphery of both lungs suggestive of pulmonary fibrosis. Chest x-ray reveals diffuse bilateral interstitial and alveolar airspace disease. Bronchoscopy washout pathology is unremarkable for malignant cells. DISCUSSION: Fluorouracil, Leucovorin with Oxaliplatin (FOLFOX) and Capecitabine with Oxaliplatin (CAPOX) are the two common therapies for stage III colon cancer [2]. Porcine model in vivo lung perfusion studies concluded dose dependent lung toxicity of fibrin deposits and white blood cell infiltrated at 72 hours with 80mg/L dose of Oxaliplatin, and evidence was proven by severe impaired P/F ratio [3]. CONCLUSIONS: This case presents a rare side effect of oxaliplatin causing Pulmonary Fibrosis. REFERENCE #1: Sohn, K.-H., et al., Incidence and Risk of Oxaliplatin-Induced Hypersensitivity in Patients with Asymptomatic Prior Exposure: A Prospective Observational Study. The Journal of Allergy and Clinical Immunology: In Practice, 2018. 6(5): p. 1642-1648.e2. REFERENCE #2: André, T., et al., Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. New England Journal of Medicine, 2004. 350(23): p. 2343-2351. REFERENCE #3: Ramadan, K., et al., A model to assess acute and delayed lung toxicity of oxaliplatin during in†vivo lung perfusion. The Journal of thoracic and cardiovascular surgery, 2020 DISCLOSURES: No relevant relationships by ASMA HAJI DATOO, source=Web Response No relevant relationships by Ajith puthillath, source=Web Response No relevant relationships by Jennifer Williams, source=Web Response