A 55-year-old man had visited another hospital in May 2010 with presenting symptoms of low abdominal pain and bowel habit change for several months. He had no history of smoking, hypertension, diabetes mellitus, hepatitis or pulmonary disease. Colonoscopy showed a recto-sigmoid colon tumor. Colonoscopic biopsy revealed a moderately differentiated adenocarcinoma. On computed tomography (CT) and positive emission tomography (PET)/CT, the tumor was shown to be located on the recto-sigmoid junction, with multiple lymph-node metastases on the left supra-clavicular, para-vertebral and para-aortic areas and with no hepatic or pulmonary metastasis. Under the diagnosis of recto-sigmoid colon cancer with multiple distant metastases of lymph nodes, a laparoscopic-assisted anterior resection was performed in that hospital. The pathology result for a specimen showed a moderately differentiated adenocarcinoma that had infiltrated the pericolic adipose tissue. Lymphatic, perineural and venous invasions were presented. Metastases of regional lymph nodes were found in 16 out of the 20 retrieved pericolic lymph nodes. The final pathologic stage was T3N2bM1, stage IV. After recovering from surgery, the patient visited our hospital for palliative treatment. FOLFOX-4 regimen (oxaliplatin with infusional 5-fluorouracil plus leucovorin)[1] was chosen and started in June 2010; targeted agents were not included because of the economic situation of the patient. Except for intermittent grade-3 neutropenia, the patient tolerated FOLFOX-4 chemotherapy well.

On the follow-up CT after the 12th cycle of chemotherapy, the multiple lymph-node metastases on the left supra-clavicular, paravertebral, and para-aortic areas had disappeared. Two weeks following the end of 13th cycle of chemotherapy, dry cough and dyspnea developed, and the symptoms rapidly worsened. On the 28th day after 13th cycle of chemotherapy, he visited the hospital due to pulmonary symptoms. Vital signs were stable with normal body temperature. On physical examination, dyspnea on exertion was presented, and inspiratory crackles were audible on both lungs. There was no chest retraction, wheezing or cyanosis. On arterial blood gas analysis (ABGA), a pH of 7.41, a PaCO₂ of 27.8 mmHg and a PaO₂ of 86.9 mmHg were shown in room air. The chest X-ray and high-resolution chest computed tomography (HRCT) demonstrated parenchymal distorsion, fibrosis and multiple patchy ground-glass opacities on both lungs (Fig. 1).

Under the suspicion of oxaliplatin-induced pulmonary toxicity, idiopathic pulmonary fibrosis, he was admitted and received broad-spectrum antibiotics and oral corticosteroid immediately. For the differential diagnosis with infectious pneumonia and malignant disease, bronchoscopy was performed. On bronchoscopic examination, there was no endobronchial lesion, and no other infection or malignancy was shown on bronchoscopic biopsy or bronchoalveolar lavage cytology. The bronchial washing culture was also negative. At the beginning of the treatment, the patient had felt better in terms of dyspnea. However, after two days of hospitalization, the dyspnea worsened; in spite of the medical treatment, the diffuse ground-glass opacities the on chest X-ray had progressed. On the 3rd hospital day, the patient was moved into the intensive care unit (ICU) and intubated, and mechanical ventilation was started. Steroid therapy was changed to intravenous methylprednisone, but the patient showed a poor clinical course and progressively worsening radiographic findings. On the 23rd hospital day, he died due to irreversible respiratory failure and multiple organ failure.

A 73-year-old man with hepatic flexure colon cancer was referred to the Department of Surgery for operation. He had a medical history of noninsulin-dependent diabetes mellitus without complications and no history of cigarette smoking. A right hemicolectomy was performed for colon cancer on the hepatic flexure in July 2009. Pathology showed a moderately differentiated adenocarcinoma that had infiltrated the pericolic adipose tissue. Lymphatic, perineural and venous invasions were not presented. Metastasis of a regional lymph node was found in 1 out of 34 retrieved pericolic lymph nodes. The final pathologic stage was T3N1M0, stage IIIB. A chest X-ray and chest CT before the initiation of chemotherapy showed an emphysematous lung on both upper lobes and the right middle lobe, but no pulmonary symptoms were present (Fig. 2). Adjuvant chemotherapy, including the FOLFOX-4 regimen, was started in September 2009. There were no specific changes on follow up after every three cycles of chemotherapy, including CT and tumor markers, during the course of the treatment.

During the 9th cycle of the FOLFOX-4 regimen, immediately after the administration of oxaliplatin, dyspnea suddenly developed on the 1st hospital day. At the time, the body temperature was 39.3℃. Pulmonary auscultation revealed inspiratory crackles in both lungs, and dyspnea on exertion was presented. Leukocytosis (23.63 × 10³/µL) with a predominance of neutrophils (94.5%) was noted on the laboratory test. C-reactive protein was elevated at 16.89 mg/dL (reference range, <0.5 mg/dL). A chest X-ray and HRCT showed ground-glass opacities in the left upper lobe and both lower lobes, and a patchy consolidation in the right middle lobe (Fig. 3). A treatment with oxygen therapy with a mask, corticosteroids and broad-spectrum antibiotics were started. Sputum and blood cultures were negative. On the test for the Swine influenza A virus, which we conducted because of a flu epidemic at the time, virus infection was negative. Based on the clinical course and imaging findings, we made a diagnosis of FOLFOX-induced interstitial pneumonitis or hypersensitivity pneumonia. He presented with progressive respiratory failure and was transferred to the ICU for mechanical ventilation on the 11th hospital day. The clinical course was unfavorable, with worsening of respiratory insufficiency, leading to the patient's death on the 18th hospital day.