The possibility that filgrastim, or the rapid increase of white blood cells, might augment bleomycin pulmonary toxicity has been discussed in the literature. Bleomycin is known to cause pulmonary toxicity in approx 10% of patients, lethal pulmonary fibrosis in approx 1-2% of patients, and nonlethal pulmonary fibrosis in 2-3% of patients (6). The incidence of pulmonary toxicity appears to increase when bleomycin is used in combination with other drugs and administered to patients with reduced renal function. The possible augmentation of bleomycin pulmonary toxicity by filgrastim has been addressed by studies in animal models (7,8) and by both nonrandomized and randomized clinical trials (9-11). Although anecdotal case reports of pulmonary adverse events have been published, the available evidence from controlled clinical trials argues against an excess morbidity in filgrastim-treated individuals. Determination of a causal relationship between filgrastim and the possible augmentation of bleomycin pulmonary toxicity is complicated in these cases by confounding variables and contributory risk factors. It should be noted that the rHuGM-CSF products have labeled precautions recommending close monitoring in patients with pulmonary disease (12).
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