Vincristine: Can its therapeutic index be enhanced?
Vincristine is one of the most widely used and more effective drugs in paediatric oncology. The dose-limiting toxicity of neuropathy, lack of proven neuroprotective measures and an incomplete understanding of the pharmacokinetics and pharmacogenetics of vincristine have limited its therapeutic potential. Recent advances in the understanding of vincristine pharmacokinetics and pharmacogenetics, and potential methods of preventing neurotoxicity are reviewed which could enable dose escalation and dose individualisation in order to enhance the therapeutic index.
Moore
Andrew
A
Section of Paediatric Oncology, The Institute of Cancer Research, Sutton, United Kingdom. andrew.moore@icr.ac.uk
Pinkerton
Ross
R
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000505:Alopecia / Q000139:chemically induced; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002648:Child; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008081:Liposomes; D009369:Neoplasms / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D011115:Polyneuropathies / Q000139:chemically induced / Q000517:prevention & control; D014404:Tubulin / Q000187:drug effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D018696:Neuroprotective Agents; D014404:Tubulin; D014750:Vincristine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human