A 24-year-old man comes to the oncology clinic for a follow-up visit. The patient was diagnosed with Hodgkin lymphoma 4 months ago and received combination chemotherapy. He has had a nonproductive cough and shortness of breath with exertion over the past 2 weeks. On examination, there is no jugular venous distension or pedal edema. Heart sounds are normal with no murmurs. Lung auscultation reveals bilateral fine inspiratory crackles. Chest radiograph shows bilateral reticular interstitial opacities. Pulmonary function testing shows a restrictive pattern with decreased diffusion capacity for carbon monoxide. Chest x-ray and pulmonary function testing prior to the initiation of chemotherapy were normal. Which of the following is the most likely mechanism of action of the medication causing this patient's current symptoms?

Question

A 24-year-old man comes to the oncology clinic for a follow-up visit.  The patient was diagnosed with Hodgkin lymphoma 4 months ago and received combination chemotherapy.  He has had a nonproductive cough and shortness of breath with exertion over the past 2 weeks.  On examination, there is no jugular venous distension or pedal edema.  Heart sounds are normal with no murmurs.  Lung auscultation reveals bilateral fine inspiratory crackles.  Chest radiograph shows bilateral reticular interstitial opacities.  Pulmonary function testing shows a restrictive pattern with decreased diffusion capacity for carbon monoxide.  Chest x-ray and pulmonary function testing prior to the initiation of chemotherapy were normal.  Which of the following is the most likely mechanism of action of the medication causing this patient's current symptoms?

Quizplus · Accepted Answer

11ec160b_3be4_6d6f_9249_8d04778b094d_MD0001_00 Bleomycin is commonly used in the treatment of Hodgkin lymphoma and germ cell tumors; it exerts an antineoplastic effect by binding with iron and oxygen molecules to create free radicals that cause DNA strand breaks. Lung toxicity, usually in the form of pulmonary fibrosis, is the most clinically important adverse effect of the drug. Toxicity from bleomycin likely results from oxidative free-radical damage to healthy tissue, leading to a cycle of tissue damage and repair. The lungs are particularly susceptible because they lack bleomycin hydrolase, an enzyme that helps inactivate bleomycin in other tissues. Patients who develop lung toxicity typically experience dyspnea, nonproductive cough, and crackles on lung auscultation within 6 months following initiation of therapy. Bibasilar interstitial opacities are typically seen on chest x-ray, and spirometry demonstrates reduced FVC with relatively preserved FEV1, consistent with a restrictive pattern. In addition, there is reduced diffusion capacity for carbon monoxide (DLCO) due to impaired gas exchange across an inflamed or fibrosed interstitium. (Choice A) Vinka alkaloids (eg, vincristine, vinblastine) bind to beta-tubulin to disrupt microtubule polymerization and prevent mitotic cell division. Peripheral neuropathy is a common adverse effect of these drugs. (Choice B) 5-fluoruracil inhibits thymidylate synthase to impair DNA synthesis. Bone marrow suppression (eg, anemia, neutropenia) can occur. (Choice D) Etoposide inhibits topoisomerase II to cause DNA strand breaks, and is commonly associated with bone marrow suppression. Anthracyclines (eg, doxorubicin) also exert at least part of their antineoplastic effect by binding to topoisomerase II and can cause cardiotoxicity that manifests as dilated cardiomyopathy. (Choice E) The tyrosine kinase inhibitors imatinib and erlotinib are used to treat chronic myelogenous leukemia and lung cancer, respectively. These drugs disrupt cellular replication and commonly cause diarrhea and skin rash. (Choice F) Proteasome inhibitors (eg, bortezomib) are used in the treatment of multiple myeloma. These drugs can cause bone marrow suppression and sometimes peripheral neuropathy. Educational objective: Bleomycin is an antineoplastic agent that binds to iron and oxygen molecules to create free radicals that cause DNA strand breaks. The most clinically important adverse effect of bleomycin is lung toxicity, usually manifesting as pulmonary fibrosis. Patients develop dyspnea and nonproductive cough, and pulmonary function testing shows a restrictive pattern with reduced diffusion capacity for carbon monoxide (DLCO). __________ References: Bleomycin-induced pulmonary toxicity. (http://www.ncbi.nlm.nih.gov/pubmed/1691067)

A 24-Year-Old Man Comes to the Oncology Clinic for a Follow-Up