Interstitial lung disease following FOLFOX + FOLFIRI and bevacizumab therapy associated with leucovorin: A case report

Chemotherapy-induced interstitial lung disease in colorectal cancer patients is rare but represents a life-threatening adverse reaction. We report here a case of interstitial lung disease following chemotherapy for metastatic colorectal cancer and the interesting results of the drug-induced lymphocyte stimulation test and leukocyte migration test. After chemotherapy with oxaliplatin plus infusional 5-fluorouracil and leucovorin (FOLFOX) plus bevacizumab followed by irinotecan plus infusional 5-fluorouracil and leucovorin (FOLFIRI), the patient was hospitalized with fever and chills. Laboratory data showed neutropenia and eosinophilia. Computed tomography revealed ground-glass opacities in both lungs; therefore, we diagnosed chemotherapy-induced interstitial lung disease. Steroid therapy was effective. We suspected irinotecan to be the etiological drug for interstitial lung disease in this patient because interstitial lung disease developed after switching the regimen from FOLFOX to FOLFIRI. However, drug-induced lymphocyte stimulation test and leukocyte migration test results were positive for only leucovorin and negative for irinotecan and 5-fluorouracil. This is the first case to show positive results on the drug-induced lymphocyte stimulation test and leukocyte migration test for only leucovorin and negative results for antineoplastic drugs. Our findings suggest that all drugs included in chemotherapy regimens have the potential to induce interstitial lung disease, and if rechallenge chemotherapy is considered, the drug-induced lymphocyte stimulation test and leukocyte migration test are expected to be useful for determining the drug that needs to be excluded.