Case of Fatal Oxaliplatin-induced Pulmonary Toxicity

Abstract INTRODUCTION: Oxaliplatin is a platinum-based medication used in treating various cancers by exhibiting cytotoxic effects on numerous cell lines primarily through blocking DNA replication and transcription. Various chemotherapy agents are known to cause pulmonary toxicity such as bleomycin, busulfan, cyclophosphamide and actinomycin-D. There are limited cases reporting oxaliplatin-induced pulmonary toxicity and among those, most cases are in the context of colorectal cancer treatment. Our case demonstrates how oxaliplatin in the treatment of pancreatic adenocarcinoma can cause progressive respiratory failure by exacerbating prior interstitial lung disease (ILD) and causing hypersensitivity pneumonitis. CASE PRESENTATION: A 78-year-old woman with stage 3A serous cystadenoma ovarian cancer had previously undergone a total abdominal hysterectomy with bilateral salpingo-oophorectomy, followed by six cycles of carboplatin and paclitaxel, remaining recurrence-free. Two years later, she presented with left upper quadrant pain, and a CT scan identified a pancreatic mass. She underwent robotic-assisted distal pancreatectomy and splenectomy, with pathology confirming pancreatic ductal adenocarcinoma. FOLFOXIRI/pegfilgrastim (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) was initiated, but due to oral blisters and ulcers, a 20% dose reduction was implemented in the second cycle. Two weeks later, respiratory distress required IV steroids and antihistamines for delayed chemotherapy hypersensitivity, necessitating desensitization for further cycles. Restaging CT showed no recurrence, but interstitial lung disease was noted. She completed five more cycles with desensitization. After cycle 8, she was readmitted with hypoxic respiratory failure, and CT revealed lung changes and cystic lesions. Despite glucocorticoids, her respiratory status deteriorated, thought to be related to oxaliplatin-induced pulmonary toxicity and hypersensitivity pneumonitis. Treatment with intravenous immunoglobulin (IVIG), antibiotics, Rituximab, and ARDS protocol was ineffective, leading to ARDS, renal failure, and multi-organ failure. The family declined further intervention and the patient passed away shortly afterwards. DISCUSSION:Oxaliplatin-induced pulmonary toxicity is a rare but potentially fatal side effect, with a mortality rate of 76.9% in mechanically ventilated patients. There are no established guidelines for this condition, thus it is difficult to diagnose and treat. Few patients showed improvement with oxaliplatin discontinuation, while others responded to glucocorticoids, N-acetylcysteine (NAC), cyclophosphamide, and IVIG. However, despite various treatments for our patient, it resulted in a fatality. We recommend monitoring patients with underlying pulmonary disease undergoing oxaliplatin treatment for pulmonary complications. Further studies and systematic review are needed to establish appropriate approaches to manage this rare but deadly complication.