Bleomycin Toxicity

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Testicular cancer is unique in that cure often requires an integration of chemotherapy and surgery. Treatment of widely metastatic disease consists of cisplatin-based chemotherapy, typically with three or four courses of cisplatin, etoposide, and bleomycin. Those patients not achieving radiographic response with residual retroperitoneal disease typically undergo post-chemotherapy surgery. It is in this setting that the urologist must confront the potential postoperative pulmonary toxicity related to bleomycin use.

Bleomycin exerts its cytotoxic effect by induction of free oxygen radicals, resulting in DNA breaks and cell death, as well as the inhibition of tumor angiogenesis. Due to the lack of the bleomycin-inactivating enzyme, bleomycin hydrolase, in the lungs and skin, bleomycin-induced toxicity occurs predominately in these organs. A multi-institutional study involving 812 testis cancer patients performed serial pulmonary function testing to define pulmonary toxicity related to bleomycin administration (de Wit et al. 2001). This study found a median acute decline in carbon monoxide diffusion capacity (DCLO) of 19% in patients who received a cumulative dose of 270 units. Chronic decline in DCLO has not been shown. The toxic death rate at this dose is less than 0.2 %, with no significant impairment in long-term pulmonary function. At doses of 360 units, the toxic death rate increased to 1 % - 2 %.

Prior bleomycin exposure has been associated with an increased risk of postoperative pulmonary compli cations including fatal acute respiratory distress syndrome (ARDS). In the 1980s and early 1990s at our institution, the postoperative management of such patients involved the judicious administration of postoperative fluid preferring oliguria and prerenal creatinine rise to the potential of ARDS. With clinical experience, improved surgical technique with decreased blood loss and operative time, we no longer limit post-operate hydration. Massively obese patients, those who have received salvage chemotherapy, or have extensive surgical dissections are at higher risk of postoperative pulmonary complications and we would recommend judicious fluid administration with monitoring of volume status.

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