B80-6-21 Collateral Damage: A Case of Respiratory Failure From Irinotecan-associated Severe Diffuse Alveolar Damage

Irinotecan, a DNA topoisomerase I inhibitor used in chemotherapy for solid tumors, is often combined with 5-fluorouracil and folinic acid as FOLFIRI in colorectal cancer treatment. While common toxicities include bone marrow suppression and gastrointestinal upset, pulmonary effects are underrecognized despite new-onset cough or dyspnea in up to 20% of US patients. Severe cases of pulmonary toxicity are increasingly reported, such as this case of profound respiratory failure after transitioning to FOLFIRI. A 66-year-old male with metastatic colon adenocarcinoma presented with new-onset dyspnea, found to be hypoxemic to 86% on room air requiring high-flow nasal cannula. History was notable for transition from oxaliplatin-based therapy to irinotecan-based therapy three months prior due to disease progression. Labs revealed acute on chronic anemia (Hgb 4.9 mg/dL), necessitating transfusion. Chest CT demonstrated diffuse ground-glass opacities with small pleural effusions. Subsequent bronchoscopy revealed bloody airways without progressively bloody return. Cytology showed rare eosinophils, without hemosiderin-laden macrophages or malignant cells. Infectious studies, including AFB cultures, were negative except for rare Enterococcus on BAL, deemed colonization. Autoimmune workup was unremarkable except for non-specific atypical p-ANCA titers (1:40). A brief empiric course of prednisone for gout flare yielded no pulmonary benefit. With infectious and rheumatologic etiologies excluded, his pulmonary parenchymal hemorrhage was attributed to irinotecan-associated diffuse alveolar damage (DAD). His course was complicated by progressive oliguric renal failure, ultimately transitioning to comfort-focused care. A broad differential was considered; however, this presentation was most consistent with irinotecan-induced DAD. Irinotecan-induced damage results from direct cytotoxic injury to pneumocytes through impaired DNA repair, compounded by inflammatory immune-mediated mechanisms, which may present weeks to months after treatment initiation. In phase II trials, irinotecan was associated with grade 3-4 dyspnea in 4% of patients. Adriani et al. highlights a possible drug interaction, with >20% pulmonary toxicity reported among those previously exposed to 5-fluorouracil. Patients with structural lung disease are also at increased risk, with Ozawa et al. reporting pre-existing interstitial lung disease (ILD) as the most predictable factor for lung injury (odds ratio 5.00, p = 0.07). In this case, rare eosinophils with bloody secretions on bronchoscopy supported drug-induced injury and bland hemorrhage. While lung biopsy could have provided diagnostic certainty, it was not pursued given his terminal illness and lack of impact on management or quality of life. Early recognition of pulmonary toxicity with Irinotecan-based therapy is critical, requiring clinicians to weigh the risks of potentially fatal pulmonary complications against oncologic benefit.