Abstract
Vincristine (VCR), an effective antitumor drug, has been utilized in several polytherapy regimens for acute lymphoblastic leukemia, neuroblastoma and rhabdomyosarcoma. However, clinical evidence shows that the metabolism of VCR varies greatly among patients. The traditional based body surface area (BSA) administration method is prone to insufficient exposure to VCR or severe VCR-induced peripheral neurotoxicity (VIPN). Therefore, reliable strategies are urgently needed to improve efficacy and reduce VIPN. Due to the unpredictable pharmacokinetic changes of VCR, therapeutic drug monitoring (TDM) may help to ensure its efficacy and to manage VIPN. At present, there is a lot of supporting evidence for the suitability of applying TDM to VCR therapy. Based on the consensus guidelines drafted by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), this review aimed to summarize various available data to evaluate the potential utility of VCR TDM for cancer patients. Of note, valuable evidence has accumulated on pharmacokinetics variability, pharmacodynamics, drug exposure–clinical response relationship, biomarkers for VIPN prediction, and assays for VCR monitoring. However, there are still many relevant clinical pharmacological questions that cannot yet be answered merely based on insufficient evidence. Currently, we cannot recommend a therapeutic exposure range and cannot yet provide a dose-adaptation strategy for clinicians and patients. In areas where the evidence is not yet sufficient, more research is needed in the future. The precision medicine of VCR cannot rely on TDM alone and needs to consider the clinical, environmental, genetic background and patient-specific factors as a whole.
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Abbreviations
- ABC:
-
ATP-binding cassette transporters
- AGNP:
-
Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie
- ALL:
-
Acute lymphocytic leukemia
- AUC:
-
The area under the plasma concentration
- BBB:
-
Blood–brain barrier
- BSA:
-
Body surface area
- CL :
-
Clearance
- CTCAE:
-
Common terminology criteria of adverse events
- CYP450:
-
Cytochrome P450
- DDI:
-
Drug–drug interaction
- HPLC:
-
High-performance liquid chromatography
- IATDMCT:
-
International association of therapeutic drug monitoring and clinical toxicology
- LC–MS/MS:
-
High-performance liquid chromatography coupled with mass spectrometry
- LLOQ:
-
Low limit of quantitation
- PBPK:
-
Physiologically based PK
- PD:
-
Pharmacodynamics
- ped-mTNS:
-
Modified total neuropathy scale
- P-gp:
-
P-glycoprotein
- PK:
-
Pharmacokinetics
- RR:
-
Relative risk
- SNPs:
-
Single nucleotide polymorphisms
- t 1/2β :
-
Elimination half-life
- TDM:
-
Therapeutic drug monitoring
- TNS:
-
Total neuropathy scale
- UHPLC:
-
Ultra-high pressure liquid chromatography
- VCR:
-
Vincristine
- V d :
-
Distribution volume
- VIPN:
-
VCR-induced peripheral neuropathy
- VSLI:
-
VCR sulfate liposomal injection
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Acknowledgements
This work was supported by Grants from the National Natural Science Foundation of China (No. 81803642), the Specially Appointed Medical Expert Project of Jiangsu Commission of Health (2019) and the Scientific Research Support Foundation for Top Young Scholars at the Children’s Hospital of Nanjing Medical University (2020).
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Conceptualization, FC, LZ and YHH; writing—original draft preparation, CYW and YHH; writing—review & editing, CF, YRW, HLG, WRF, TL and GTL; funding acquisition, YHH and FC. All authors have read and agreed to the published version of the manuscript.
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Chun-Ying Wu and Chen-Chao Chu Visiting graduate student from China Pharmaceutical University.
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Wu, CY., Li, GT., Chu, CC. et al. Proactive therapeutic drug monitoring of vincristine in pediatric and adult cancer patients: current supporting evidence and future efforts. Arch Toxicol 97, 377–392 (2023). https://doi.org/10.1007/s00204-022-03418-8
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DOI: https://doi.org/10.1007/s00204-022-03418-8