A retrospective analysis of neurotoxicity induced by vinca alkaloids combined with azole anti-fungal agents in hematological malignancies

• Published in: Gan to kagaku ryoho Vol. 38; no. 10; p. 1667
• Main Authors: Osato, Yoichi, Yokoyama, Tomohisa, Saito, Yumiko, Kani, Rinako, Hayabe, Hiroko, Miyamatsu, Hironobu, Ohyashiki, Kazuma
• Format: Journal Article
• Language: Japanese
• Published: Japan 01.10.2011
• Subjects: Adult; Aged; Aged, 80 and over; Antifungal Agents - administration & dosage; Antifungal Agents - adverse effects; Antifungal Agents - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Azoles - administration & dosage; Azoles - adverse effects; Azoles - therapeutic use; Female; Hematologic Neoplasms - drug therapy; Humans; Male; Middle Aged; Neurotoxicity Syndromes; Retrospective Studies; Vinca Alkaloids - administration & dosage; Vinca Alkaloids - adverse effects; Vinca Alkaloids - therapeutic use; Young Adult
• ISSN: 0385-0684

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.