Severe Pulmonary Toxicity in a Patient Treated With Gemcitabine Manuel F. Rosado, M.D., Daniel H. Kett, M.D., Roland M. H. Schein, M.D., Francisco J. Baraona, M.D., and Kasi S. Sridhar, M.D. Gemcitabine is a pyrimidine analog of deoxycytidine with activity against nonhematologic and hematologic malignancies. Its pulmonary toxicity is usually mild and self-limiting. We describe a male patient with lung cancer in whom severe dyspnea and interstitial infiltrates developed after the adminis- tration of gemcitabine. Key Words: Gemcitabine—Pulmonary toxicity. Gemcitabine (2', 2'-difluorodeoxycitidine) is a pyrim- idine analog of deoxycytidine with antitumor activity against nonhematologic and hematologic malignan- cies. 1,2 In phase II trials, response rates in the 16% to 24% range were reported in patients with non–small-cell lung cancer previously untreated and small-cell lung cancer previously treated. 3 Gemcitabine has mild sys- temic toxicities, and well-known pulmonary toxicity when it is used with concomitant radiotherapy, but only a few cases of severe pulmonary toxicity have been described when this drug is used alone. 4–8 We describe the clinical course of a male patient with lung cancer in whom severe dyspnea and interstitial infiltrates devel- oped secondary to gemcitabine. CASE REPORT An 85-year-old man with a history of diabetes mellitus was incidentally diagnosed with stage IV non–small-cell lung cancer in November 1999 when a chest radiograph showed a mass in the right lung. Computed tomography of the chest scanning revealed, in addition to the right midlung mass, contralateral lung involvement and liver metastasis, and the lung biopsy revealed adenocarci- noma. The patient received two cycles of carboplatin AUC 6 and paclitaxel 175 mg/m 2 with progressive dis- ease. Treatment with gemcitabine was started, 1,000 mg/m 2 on days 1, 8, and 15 every 4 weeks with premed- ication consisting of granisetron, but no steroids were used because of his diabetes. He had clinical improve- ment and partial radiologic response on follow-up. The patient was admitted to another hospital on day 5 of cycle 2 of gemcitabine because of a syncopal episode and 1-week history of dyspnea. On electrocardiogram, he was found to have right bundle branch block and left anterior fascicular block, and myocardial infarction was ruled out by three sets of cardiac enzymes and serial electrocardiograms. The patient sought treatment at our institution because of worsening dyspnea, fatigue, and a persistent, dry cough. He could not recall having fever, chills, or night sweats. On physical examination, the patient was afebrile, cyanotic, tachypneic (34 breaths/ min), and he had crackles in both lung bases. His hemo- globin level was 12.8 g/dl, his leukocyte count was 16,140/l with 90% neutrophils, and his platelets count was 251,000/l. Partial pressure of oxygen was 69 mm Hg and of CO 2 was 29 mm Hg with oxygen saturation of 95% on 6 l of oxygen via nasal canula. Chest radiogra- phy showed new, diffuse interstitial and alveolar infil- trates throughout both lungs. The alveolar infiltrates were more confluent in the left lower lobe and in the right upper lobe. Bilateral pleural effusions were also present (Fig. 1). The patient was admitted to the inten- sive care unit and required mechanical ventilation. Computed tomography scanning of the chest revealed bilateral extensive ground-glass opacity involving the en- tire left lung and portions of the right lung. There was interstitial prominence identified throughout, which was consistent with hypersensitivity pneumonitis, and decrease of the right lung mass with no evidence of tumor in the left lung was also noticed (Fig. 2). The bronchoscopy revealed only scant secretions, and the bronchoalveolar lavage showed cellular evidence of acute inflammation; malignant cells were not identified. Unfortunately, a transbronchial biopsy could not be done safely. The patient began receiv- ing intravenous antibiotics and methylprednisolone 60 mg intravenously every 6 hours. Bacterial, viral, fungal, and acid-fast-cultures were negative, so antibiot- ics were discontinued. After initial improvement, the patient became septic and required broad-spectrum anti- biotics and vasopressors. There was a clinical worsening, Departments of Medicine (M.F.R.) and Critical Care (D.H.K., R.M.H.S.), and Pulmonary Department (F.J.B.), Jackson Memorial Hospital, University of Miami School of Medicine, and Division of Hematology-Oncology (K.S.S.), University of Miami Sylvester Com- prehensive Cancer Center, Miami, Florida, U.S.A. Address correspondence and reprint requests to Dr. Manuel F. Rosado, Department of Medicine, Jackson Memorial Hospital, 1611 NW 12th Avenue, Miami, FL 33136-1094, U.S.A. Am J Clin Oncol (CCT) 25(1): 31–33, 2002. © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia 31