Q&A: Vascular Complications Of Cytotoxics: Pulmonary Veno-Occlusive Disease

Development of new anticancer drugs has resulted in improved mortality rates and 5-year survival rates in patients with cancer. However, many of the modern chemotherapies are associated with cardiovascular toxicities that increase cardiovascular risk in cancer patients.

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In this article:
Pulmonary veno-occlusive complication of cytotoxics
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

Pulmonary veno-occlusive complication of cytotoxics

Recognition of hepatic veno-occlusive disease (HVOD) as a complication of antineoplastic chemotherapy was followed by reports of a similar association between pulmonary veno-occlusive disease (PVOD) and a variety of chemotherapy regimens.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterised by preferential remodelling of the pulmonary venules. In pulmonary veno-occlusive disease, there is blockage (occlusion) of the blood vessels that carry oxygen-rich (oxygenated) blood from the lungs to the heart (the pulmonary veins). The occlusion is caused by a buildup of abnormal fibrous tissue in the small veins in the lungs, which narrows the vessels and impairs blood flow. Because blood flow through the lungs is difficult, pressure rises in the vessels that carry blood that needs to be oxygenated to the lungs from the heart (the pulmonary arteries). Increased pressure in these vessels is known as pulmonary arterial hypertension.

Exposures to chemotherapeutic agents, chemotherapeutic regimens, and certain toxins, including cigarette smoke, have been reported to be associated with PVOD.

MCQ exam: clinical scenario

Vascular abnormalities are a known side effect of several cytotoxic drugs.

Which of the following cytotoxic drugs is most likely to lead to pulmonary veno-occlusive disease?

a) Bleomycin
b) 5-Fluorouracil
c) Taxoids
d) Cyclopentenyl cytosine
e) Trastuzumab

MCQ exam: answer

The correct answer is A.
Bleomycin commonly results in pulmonary toxicity and progressive pulmonary fibrosis.

MCQ exam: explanation

There are at least 40 drugs which may produce adverse pulmonary effects.

The more common ones are bleomycin, busulfan, mitomycin, carmustine (BCNU), cisplatin, mechlorethamine, vincristine, procarbazine, and cyclophosphamide. Others are arabinoside, Interleukin-2 (IL2) and methotrexate.

The clinical features are dyspnoea, cough, pulmonary infiltrates, basal inspiratory crackles, and, rarely, pleural friction rub, pleural effusions, pulmonary fibrosis and eosinophilia.

Bleomycin exerts anticancer effects by damaging DNA and disrupting the cytoskeleton. It causes a dose-dependent reduction in endothelial cell growth and induction of apoptosis. These vascular toxic effects at least in part explain associated cardiovascular complications including myocardial ischemia and infarction, thrombosis and thromboembolism, pulmonary fibrosis, and Raynaud phenomenon.

Reference(s)
1). UpToDate: Epidemiology, pathogenesis, clinical evaluation, and diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis in adults. Available online: https://www.uptodate.com/contents/epidemiology-pathogenesis-clinical-evaluation-and-diagnosis-of-pulmonary-veno-occlusive-disease-pulmonary-capillary-hemangiomatosis-in-adults
2). US National Library of Medicine: Pulmonary veno-occlusive disease. Available online: https://ghr.nlm.nih.gov/condition/pulmonary-veno-occlusive-disease
3). David Montani, et al: Pulmonary veno-occlusive disease. European Respiratory Journal 2016 47: 1518-1534; DOI: 10.1183/13993003.00026-2016. Available online: https://erj.ersjournals.com/content/47/5/1518