US Pharm. 2015;40(5):HS-32-HS-33.
Researchers have identified the first genetic variation that is associated with increased risk and severity of peripheral neuropathy following treatment with a widely used anticancer drug. The scientists also found evidence of how it may be possible to protect young leukemia patients without jeopardizing cures. Scientists from St. Jude Children’s Research Hospital led the study, which appears in the Journal of the American Medical Association.
The study involved 321 children and adolescents with acute lymphoblastic leukemia (ALL) who were treated with 36 to 39 doses of the drug vincristine.
Researchers screened patient DNA for almost 1 million common inherited genetic variations and found that 60.8% of patients who inherited two copies of a variation in a gene called CEP72 developed peripheral neuropathy. Vincristine-related peripheral neuropathy was diagnosed in 23.4% of patients who inherited at least one of the more common versions of CEP72. Patients with two copies of the high-risk CEP72 variant were also more than twice as likely as other patients to experience serious, disabling, or life-threatening peripheral neuropathy.
The CEP72 variant, the scientists found, also increased the sensitivity of cancer cells to vincristine. “That suggests it might be possible to lower the vincristine dose in these patients without compromising the likelihood of cures,” said the corresponding author William Evans, PharmD, a member of the St. Jude Department of Pharmaceutical Sciences. The possibility will be examined in a St. Jude clinical trial for newly diagnosed pediatric ALL patients scheduled to begin later this year.
