Busulfan, pulmonary toxicity

CALCIUM CHANNEL BLOCKERS BUSULFAN t plasma concentrations of busulfan and t risk of toxicity of busulfan such as veno-ocdusive disease and pulmonary fibrosis, when co-administered with diltiazem, nifedipine or verapamil Due to inhibition of CYP3A4-mediated metabolism of busulfan by these calcium channel blockers. Busulfan clearance may be l by 25%, and the AUC of busulfan may t by 1500 p,mol/L Monitor clinically for veno-ocdusive disease and pulmonary toxicity in transplant patients. Monitor busulfan blood levels as AUC of below 1500 p,mol/L per minute tends to prevent toxicity... 

Schallier D, Impens N, Warson F, Van Belle S, De Wasch G. Additive pulmonary toxicity with melphalan and busulfan therapy. Chest 1983 84(4) 492-3. 

Answer A. It can help to know which anticancer drugs are cell-cycle specific and which have characteristic toxicities. Bleomycin fits both categories acting mainly in G2, it is cell cycle specific and is distinctive for causing mucocutaneous reactions and pulmonary dysfunction. Busulfan and procarbazine may also cause pulmonary toxicity, but neither drug is cell-cycle specific. 

The pulmonary toxicity of busulfan was first reported in 1961. No clear risk factors for the development of lung toxicity have been consistently identified. The reported incidence of lung toxicity is 6% (4). The onset is typically subacute with fever and dry cough. Bleomycin is histologically characterized by NSIP or UIP. Pulmonary veno-occlusive disease and DIP have also been reported (1). Occasionally, busulfan may lead to alveolar proteinosis secondary to massive deposition of intracellular debris. This form of alveolar proteinosis is poorly responsive to whole lung lavage, and the role of steroids is not clearly estabhshed (9). 

At usual therapeutic dosages, busulfan is selectively toxic to granulocyte precursors rather than lymphocytes. Thrombocytopenia and anemia and less commonly, nausea, alopecia, mucositis, and sterility also may occur. Unusual side effects of busulfan include gynecomastia, a general increase in skin pigmentation, and interstitial pulmonary fibrosis. 

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