Refractory Gemcitabine-Induced Pneumonitis in Metastatic Testicular Cancer

Abstract Introduction Gemcitabine is a chemotherapy drug that inhibits DNA synthesis. Pneumonitis is rarely associated with gemcitabine at a 1.1% incidence. Gemcitabine-induced pneumonitis is a clinical diagnosis, and corticosteroids is standard treatment. However, literature regarding gemcitabine-induced pneumonitis refractory to steroid use is lacking. We report a case of metastatic germ cell tumor with gemcitabine-induced pneumonitis refractory to high-dose steroids. Case Description A 30-year-old male with a history of recurring seminal germ cell tumor metastatic to the lungs presented to our hospital with worsening dyspnea. He had been on palliative gemcitabine + oxaliplatin for several months with his last dose 10 days prior. A week prior, he was hospitalized for gemcitabine-induced pneumonitis, and discharged with prophylactic trimethoprim/sulfamethoxazole and 60 mg of oral prednisone with a weekly taper. The chemotherapy regimen was switched from gemcitabine + oxaliplatin to bevacizumab + oxaliplatin. Despite these changes, his dyspnea worsened, requiring high-flow nasal cannula. He was admitted to our hospital for acute on chronic respiratory failure. Treatment included prophylactic trimethoprim/sulfamethoxazole, oral prednisone at 1 mg/kg, bronchodilators, and broad-spectrum antibiotics. Diagnostic tests for viral and atypical pneumonias were negative. Computed tomography (CT) of the chest revealed bilateral patchy ground-glass opacities that were not present on previous CT chest, suggesting progressive pneumonitis. His respiratory status worsened, necessitating intubation and mechanical ventilation. Corticosteroids were increased to 1.5 mg/kg, and empirical intravenous voriconazole was initiated. He was transferred to an outside hospital for higher level of care. Follow-up bronchoalveolar lavage (BAL) studies and other infectious workup were negative for legionella, acid-fast bacteria, fungal organisms, mycobacterium tuberculosis, and pneumocystis jirovecii.Discussion Systemic corticosteroids are the first-line therapy for drug-induced pneumonitis, with low-dose corticosteroids (0.5-1 mg/kg/day) for mild cases and higher doses of prednisone (1-2 mg/kg/day) in severe cases. For very severe cases, intravenous corticosteroids or immunosuppressants may be necessary if symptoms persist, tapering gradually to prevent relapse. Our case reflects a patient with delayed diagnosis and treatment, refractory to even higher doses of prednisone. This suggests that delaying diagnosis and corticosteroid initiation can result in life-threatening respiratory compromise in gemcitabine-induced pneumonitis. While an extensive pneumonia workup may be necessary in these immunosuppressed patients, it should not delay initiation or uptitration of corticosteroids. Conclusion Clinicians should remain vigilant when treating gemcitabine-induced pneumonitis. Future research should focus on optimal initiation, dosing, and duration of corticosteroids to positively impact respiratory status in this immunosuppressed population.