Vincristine Induced Toxicities Secondary to Azole Antifungal Therapy in Patients with ...

25 Pages·2010·0.7 MB·English

Vincristine-Induced Toxicities Secondary
to Azole Antifungal Therapy in Patients
with Hematologic Malignancies
Kara E. Loth, PharmD
PGY2 Oncology Resident
Wake Forest University Baptist Medical Center
Winston-Salem, NC
Disclosure
Disclosure statement: these individuals have the
following to disclose concerning possible financial or
personal relationships with commercial entities (or
their competitors) that may be referenced in this
presentation.
Resident: Kara Loth (nothing to disclose)
Project Director, Advisor(s), & Co-Investigators:
Brandy Strickland, Gregory Russell, Kevin Buckley,
LeAnne Kennedy (nothing to disclose)
Wake Forest University Baptist
Medical Center
 Winston-Salem, NC
 Academic teaching
facility
 872 acute care beds
 NCI-designated
Comprehensive
Cancer Center
Vincristine (Oncovin®)
 Vinca alkaloid used in treating many
hematologic malignancies
• Acute Lymphoblastic Leukemia (ALL)
• Non-Hodgkin’s Lymphoma (NHL)
 Common Toxicities
• Peripheral neuropathy
• Seizure
• Constipation
• Ileus
• Hyperbilirubinemia
1Harnicar S, Adel N, Jurcic J. J Oncol Pharm Practice. 2009;00:1-8.
Antifungal Prophylaxis
 National Comprehensive Cancer Network
Guidelines
• Antifungal prophylaxis during induction and
consolidation therapy for adult leukemia
patients
 WFUBMC Practice
• Leukemia and lymphoma patients
• Fluconazole prophylaxis
Brahm HS, Lindsey RB, Corey C, et al. Prevention and treatment of cancer related infections. NCCN Clinical Practice Guidelines in
Oncology. http://www.nccn.org/professionals/ physician_gls/ PDF/infections.pdf. Accessed November 10, 2009.
Potential Drug Interaction
 Vincristine (VCR) is metabolized by cytochrome
P450 enzymes
 Azole antifungals are cytochrome P450 substrates
and inhibitors
 Azole antifungals may inhibit the metabolism of
vincristine
Gubbins PO. Current Opinion in Infectious Diseases. 2007;20:579-586.
Purpose
Evaluate the incidence of toxicity and dosage
modifications in patients receiving vincristine
and azole antifungal therapy compared to
vincristine therapy alone
Study Objectives
 Primary
•
Incidence of vincristine toxicity
 Nervous system disorders
 Gastrointestinal disorders
 Hyperbilirubinemia
 Secondary
•
Incidence of vincristine dosage modifications
 Dosage reductions
 Dose held or omitted
Methods
 Retrospective, cohort study
 Patients identified from a computer-generated list
 IRB-approved
Inclusion Criteria Exclusion Criteria
Adult and pediatric patients with ALL Concurrent therapy with a strong
and NHL cytochrome P450 inhibitor other
than an azole antifungal
Vincristine ± concurrent fluconazole
or voriconazole
Treatment between July 2005 and
June 2009
Data Collection
• Patient demographics
• Azole antifungal administered
• Potential causes of peripheral neuropathy
• Opioid use
• Iron supplementation
• Bowel regimen
• Total bilirubin
• Vincristine dosage reductions
• Vincristine toxicities