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Nitrosourea-induced pulmonary injury

Author
Ronan O'Driscoll, BSc, MD, FRCP
Section Editors
Kevin R Flaherty, MD, MS
James R Jett, MD
Deputy Editors
Helen Hollingsworth, MD
Diane MF Savarese, MD

INTRODUCTION

The nitrosourea drugs, a class of DNA alkylating agents related to nitrogen mustards, include carmustine (BCNU), lomustine (CCNU), semustine (methyl CCNU), and chloroethylnitrosourea (Sar-CNU). Nitrosourea drugs are used to treat lymphoma, brain tumors, melanoma, and other solid tumors including breast cancer. Carmustine is the most widely used nitrosourea, and is associated with acute and chronic pulmonary toxicity [1-4]. Pulmonary fibrosis has also followed treatment with semustine and chloroethylnitrosourea [5,6].

Most patients develop pulmonary fibrosis within three years of carmustine treatment; however, some patients develop breathlessness and aggressive fibrosis decades after exposure [1-4]. The reported incidence of carmustine-induced pulmonary toxicity has ranged from 20 to 30 percent in some studies, to as low as 1 percent in others [1]. The low incidence of pulmonary fibrosis in some series may be due to a short observation period, low dose carmustine therapy, or the short median survival of patients with aggressive tumors [7].

Carmustine is also used in the management of patients with lymphoma who require high dose chemotherapy in conjunction with hematopoietic stem cell support [8]. Patients who received carmustine as part of their preparative regimen for hematopoietic stem cell transplantation have a longer window for the development of pulmonary complications. In this setting the incidence of interstitial pneumonitis or idiopathic pneumonia has been reported to be 2 to 23 percent [9-11].

Some authors have suggested that this syndrome should be considered "idiopathic pneumonia syndrome" in the context of hematopoietic stem cell transplantation, because the etiology and histology of the lung abnormality are poorly characterized in many cases [12]. In addition, these patients are exposed to a single dose or short course of carmustine in combination with other chemotherapy agents, whereas use of carmustine for other disorders requires repeated cycles of chemotherapy over a period of up to two years. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation", section on 'Idiopathic pneumonia syndrome'.)

EARLY ONSET LUNG FIBROSIS

Up to 25 percent of patients in whom carmustine is administered will develop pulmonary fibrosis during the ensuing 36 months, if they survive their malignancy [1-3,7,9,10,13,14]. Lung fibrosis is especially likely with very high doses (above 1500 mg per square meter), the concurrent administration of other agents with pulmonary toxicity (such as cyclophosphamide), and possibly by preexisting lung disease, localized chest wall radiotherapy, or atopy [11].

                  

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Literature review current through: Nov 2016. | This topic last updated: Mon Jan 07 00:00:00 GMT+00:00 2013.
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