Document Detail

Modification of vincristine dosing during concomitant azole therapy in adult acute lymphoblastic leukemia patients.
MedLine Citation:
PMID:  19282418     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Vincristine is an important component in the treatment of acute lymphoblastic leukemia (ALL) and is now the backbone of therapy in the induction and consolidation phases of this disease. Proper dosing of vincristine is required to maximize disease control while avoiding toxicity. The gastrointestinal toxicity of vincristine such as decreased peristalsis can potentially be increased if the CYP 3A4 enzyme is inhibited. This interaction may become more prevalent with increasing use of CYP 3A4 inhibitors such as the azole antifungals. Since azoles are increasingly being used for prophylaxis and treatment of fungal infections in this patient population, an assessment of vincristine dosing and toxicity is the first step to constructing guidelines for the coadministration of these agents. METHODS: ALL patients !18 years of age receiving vincristine-based therapy from August 2003 through December 2007 with or without azole therapy were included. Data was collected using electronic patient medical records and the pharmacy system (RxTFC). Information was entered into a database for this retrospective study. Patients were separated into two arms; vincristine with azoles and vincristine only. Patient demographic information, chemotherapy regimen, vincristine-induced symptoms, and concurrent strong CYP 3A4 inhibitors and inducers were collected. RESULTS: A total of 50 patients received vincristine of which 29 (58%) had concurrent azole therapy. No patients received concurrent major CYP 3A4 inhibitors and the baseline characteristics were similar between groups. Vincristine dosing modifications were more common in the azole group (58.6 vs. 23.8%; p = 0.02). The mean dose reduction of vincristine when combined with an azole was 46.5%. Symptoms of decreased peristalsis were more common in patients receiving azoles (65.5 vs. 28.6%; p = 0.019) and on average occurred after the second vincristine dose. Symptoms occurred in 50, 75, and 66.6% of patients receiving fluconazole, voriconazole, and posaconazole, respectively. Patients were more likely to have an incomplete course of vincristine when receiving azole therapy (48.3 vs. 9.5%; p = 0.004). CONCLUSION: Caution should be used with the coadministration of vincristine and azoles. It is recommended that institutional guidelines be developed to standardize care for patients receiving vincristine with azole therapy. Potential measures to avoid this interaction include revisiting azole prophylaxis in this patient group and being judicious in azole selection.
Stephen Harnicar; Nelly Adel; Joseph Jurcic
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2009-03-12
Journal Detail:
Title:  Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners     Volume:  15     ISSN:  1078-1552     ISO Abbreviation:  -     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-31     Completed Date:  2009-10-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9511372     Medline TA:  J Oncol Pharm Pract     Country:  England    
Other Details:
Languages:  eng     Pagination:  175-82     Citation Subset:  IM    
Department of Pharmacy, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
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MeSH Terms
Aged, 80 and over
Antifungal Agents / administration & dosage*
Antineoplastic Agents, Phytogenic / administration & dosage*,  adverse effects
Drug Interactions
Fluconazole / administration & dosage*
Middle Aged
Peristalsis / drug effects
Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications,  drug therapy*
Pyrimidines / administration & dosage*
Retrospective Studies
Triazoles / administration & dosage,  therapeutic use*
Vincristine / administration & dosage*,  adverse effects,  therapeutic use
Reg. No./Substance:
0/Antifungal Agents; 0/Antineoplastic Agents, Phytogenic; 0/Pyrimidines; 0/Triazoles; 0/voriconazole; 57-22-7/Vincristine; 86386-73-4/Fluconazole

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