Taxol toxicity. Epithelial necrosis in the gastrointestinal tract associated with polymerized microtubule accumulation and mitotic arrest

Abstract

Taxol, an antineoplastic agent with a novel mechanism of action, is currently undergoing Phase I trials at The Johns Hopkins Hospital, Baltimore. The authors recently observed striking mitotic arrest associated with epithelial necrosis and ulceration in an esophageal biopsy specimen. The biopsy specimen was taken from a patient who received taxol the day before endoscopy. Review of our autopsy files revealed four other cases in which taxol had been administered. Sections of esophagus, stomach, small intestine, colon, liver, skin, bone marrow, and testes were examined for evidence of mitotic arrest. Mitotic arrest was seen in the two patients who underwent autopsy who received taxol less than 11 days before death, whereas the two autopsy patients who received taxol more than 2 weeks before death did not show these changes. Although mitotic arrest was most prominent in the esophagus, it was also found in the stomach, small intestine, colon, liver, and bone marrow. The mitotic arrest was associated with bundling of intermediate filaments and appeared to be secondary to accumulation of polymerized microtubules. These results suggest that taxol induces a transient mitotic arrest associated with cell necrosis.