Miya T, Fujikawa R, Fukushima J, Nogami H, Koshiishi Y, Goya T
Department of Surgery II, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Jpn J Clin Oncol. 1998 Nov;28(11):709-11. doi: 10.1093/jjco/28.11.709.
Irinotecan chloride (CPT-11) is a new semi-synthetic camptothecin analogue which has encouraging antitumor activity against various malignancies. The major and unique toxicity of CPT-11 is diarrhea. Cardiovascular toxicity is rare and has not been found in clinical trials performed in Japan except for a very few cases of insignificant tachycardiac arrhythmia. We report a case of a 69-year-old man with recurrent colon cancer who suffered from bradycardia induced by infusion of CPT-11. Other toxicities including hematological toxicity and diarrhea were mild. Pharmacokinetic analysis using a limited sampling model revealed that the occurrence of bradycardia did not correlate with the excess of drug exposure. Although all of the cholinergic actions reported in the literature were mild, cardiotoxicity may come to be a clinically significant problem. If the events were examined more thoroughly, the cholinergic effect may be discovered more frequently. To administer CPT-11 safely needs meticulous monitoring not only for hematological toxicity and diarrhea but also for other cholinergic actions including bradycardia.
伊立替康(CPT-11)是一种新型半合成喜树碱类似物,对多种恶性肿瘤具有令人鼓舞的抗肿瘤活性。CPT-11的主要且独特的毒性是腹泻。心血管毒性罕见,在日本进行的临床试验中除了极少数不显著的快速性心律失常病例外未发现。我们报告一例69岁复发性结肠癌男性患者,在输注CPT-11时出现心动过缓。包括血液学毒性和腹泻在内的其他毒性较轻。使用有限采样模型进行的药代动力学分析显示,心动过缓的发生与药物暴露过量无关。尽管文献中报道的所有胆碱能作用均较轻,但心脏毒性可能会成为一个具有临床意义的问题。如果对这些事件进行更全面的检查,胆碱能效应可能会更频繁地被发现。安全使用CPT-11不仅需要对血液学毒性和腹泻进行细致监测,还需要对包括心动过缓在内的其他胆碱能作用进行监测。