Imatinib mesylate toxicity

Dr. Guy B. Faguet is particularly keen on imatinib mesylate, or Gleevec, against CML and is an advocate of the more fundamental gene therapy rather than the cell-toxic chemotherapy (e.g., Faguet, 2005, p. 46). He also notes it to be an inhibitor for tyrosine kinase. Interestingly, he skips the Warburg theory about cancer metabolism vs. normal cell metabolism and of enzymes and enzyme inhibitors. 

A 74-year-old man with chronic myeloid leukemia took imatinib mesylate 400 mg bd. His other medications were perindopril and ator-vastatin. After 2 months he developed angio-edema, probably related to perindopril, which was withdrawn and replaced by amlodipine 10 mg/day. After 2 weeks he developed typical symptoms of imatinib toxicity nausea, marked periorbital, and ankle edema. Diuretics improved the edema, but after 10 days he complained of numbness of the chin and bilateral pain and numbness in the soles of the feet. Light touch and vibration sense were reduced, but power and reflexes were intact. Imatinib was reduced to 400 mg/day and amlodipine was withdrawn. The edema, numbness and neuropathic pain resolved. Despite residual plantar numbness he was able to increase the dose of imatinib to 600 mg/day without worsening symptoms. About 1 month later he took two doses of amlodipine in error and developed nausea and palpitation, which resolved when the amlodipine was withdrawn. Nerve conduction testing 1 month later showed a mild sensorimotor axonal neuropathy. After 9 months the neuropathy had resolved despite continuing imatinib therapy. 

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