Osato Yoichi, Yokoyama Tomohisa, Saito Yumiko, Kani Rinako, Hayabe Hiroko, Miyamatsu Hironobu, Ohyashiki Kazuma
Department of Pharmacy, Tokyo Medical University Hospital, Japan.
Gan To Kagaku Ryoho. 2011 Oct;38(10):1667-72.
Vinca alkaloids (VA) are some of the key anti-tumor agents for patients with hematological malignancies, and various adverse events such as paralytic ileus, peripheral neuropathy, and constipation were now recognized as adverse VA effects. Furthermore, azole anti-fungal agents are known to enhance VA toxicity because they delay the metabolism and excretion of VA by inhibiting CYP3A4. However, their clinical relationship has not been clearly described. Therefore, we studied neurotoxicity as a possible adverse event associated with VA in patients treated with azole anti-fungal agents, retrospectively. In our study, 100 patients (479 episodes) who received VA in our department from August 2008 to December 2010 were analyzed. Adverse events attributed to the combined administration of vincristine (VCR) and azole anti-fungal agents were grade 3 paralytic ileuses in 8 patients (8 episodes), grade 3 or 4 constipation in 16 patients (16 episodes), and grade 3 peripheral neuropathy in 10 patients (16 episodes). In addition, we investigated whether temporal discontinuation of azole anti-fungal agents during VA treatment decreases the frequency of these adverse events, and detected that it is likely to help avoid neurotoxicities enhanced by itraconazole, such as severe constipation (p=0. 0308) and paralytic ileus (p=0. 0967). Our findings indicated that we should pay much more attention to these adverse events, and must select patients carefully when we administer azole anti-fungal agents to them while they are being treated with VA.
长春花生物碱（VA）是血液系统恶性肿瘤患者的一些关键抗肿瘤药物，现在各种不良事件，如麻痹性肠梗阻、周围神经病变和便秘，都被认为是VA的不良反应。此外，已知唑类抗真菌药物会增强VA的毒性，因为它们通过抑制CYP3A4来延迟VA的代谢和排泄。然而，它们之间的临床关系尚未得到明确描述。因此，我们回顾性研究了在接受唑类抗真菌药物治疗的患者中，神经毒性作为与VA相关的一种可能不良事件的情况。在我们的研究中，分析了2008年8月至2010年12月在我们科室接受VA治疗的100例患者（479次用药）。归因于长春新碱（VCR）与唑类抗真菌药物联合使用的不良事件包括：8例患者（8次用药）出现3级麻痹性肠梗阻，16例患者（16次用药）出现3级或4级便秘，10例患者（16次用药）出现3级周围神经病变。此外，我们研究了在VA治疗期间暂时停用唑类抗真菌药物是否会降低这些不良事件的发生频率，并发现这可能有助于避免由伊曲康唑增强的神经毒性，如严重便秘（p = 0.0308）和麻痹性肠梗阻（p = 0.096）。我们的研究结果表明，我们应该更加关注这些不良事件，并且在给正在接受VA治疗的患者使用唑类抗真菌药物时，必须仔细选择患者。
