International Association of
Therapeutic Drug Monitoring and Clinical Toxicology
Fostering education, research and practice in TDM and CT

TDM in Oncology

Gareth Veal

Chair

Gareth Veal
Newcastle upon Tyne, UK

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Scientific Committees
TDM in Oncology Committee

D.J.A.R. Moes

Vice-Chair

D.J.A.R. Moes
Leiden University Medical Center, The Netherlands

Background & Purpose of the Committee

  • Creating and promoting awareness of the need for TDM in cancer therapy,
  • Stimulating studies which demonstrate the utility in improving patient outcomes,
  • Education of the IATDMCT members on advances and opportunities in the area,
  • Education of medical oncologists and regulatory authorities of the importance of TDM in oncology,
  • Development of consensus guidelines for implementation in oncology.

Scope of the Oncology Committee is:

  • TDM for cancer treatment in hematology and oncology,
  • Chemotherapy, molecular targeting therapy, hormonal therapy and immunotherapy,
  • Topics relating to drug concentrations in blood, pharmacogenomics and other biomarkers for the benefit of precision medicine.

Activities Planned/Committee Initiatives Currently in Progress

  • Consensus guideline document for TDM of busulfan
  • Consensus guideline document for TDM of imatinib
  • Consensus guideline document for TDM of paclitaxel
  • Support for future IATDMCT meeting workshops and symposia

Past Years' Activities Held/Committee Initiatives

  • Publication of consensus guideline document for TDM of Imatinib
  • Support for Rome meeting with workshops and symposia

Publications, Scientific Contributions

IATDMCT Oncology Committee Member Publications 2021

Aghai F, Zimmermann S, Kurlbaum M, Jung P, Pelzer T, Klinker H, Isberner N, Scherf-Clavel O. Development and validation of a sensitive liquid chromatography tandem mass spectrometry assay for the simultaneous determination of ten kinase inhibitors in human serum and plasma. Anal Bioanal Chem. 2021 413: 599-612 (https://doi.org/10.1007/s00216-020-03031-7)

Antunes MV, Linden R, Schaiquevich P. Therapeutic drug monitoring in developing nations: assessing the current state of affairs in South America. Expert Opin Drug Metab Toxicol. 2021 17: 251-254. (doi:10.1080/17425255.2021.1859478)

Barnett S, Errington J, Sludden J, Jamieson D, Poinsignon V, Paci A, Veal GJ. Pharmacokinetics and pharmacogenetics of cyclophosphamide in a neonate and infant childhood cancer patient population. Pharmaceuticals 2021 14: 272 1-11 (https://doi.org/10.3390/ph14030272)

Barnett S, Hellmann F, Parke E, Makin G, Tweddle DA, Osborne C, Hempel G, Veal GJ. Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients. Eur J Cancer 2021 (In press) (https://doi.org/10.1016/j.ejca.2021.09.014)

Barnett S, Kong J, Makin G, Veal GJ. Over a decade of experience with carboplatin therapeutic drug monitoring in a childhood cancer setting in the United Kingdom. Br J Clin Pharmacol 2021 87: 256-262 (https://doi.org/10.1111/bcp.14419)

Chatelut E, Hendrikx JJMA, Martin J, Ciccolini J, Moes DJAR. Unraveling the complexity of therapeutic drug monitoring for monoclonal antibody therapies to individualize dose in oncology. Pharmacol Res Perspect. 2021 9: e00757

Chevreau C, Massard C, Flechon A, Delva R, Gravis G, Lotz JP, Bay JO, Gross-Goupil M, Fizazi K, Mourey L, Paci A, Guitton J, Thomas F, Lelièvre B, Ciccolini J, Moeung S, Gallois Y, Olivier P, Culine S, Filleron T, Chatelut E. Multicentric phase II trial of TI-CE high-dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors. Cancer Med. 2021 10: 2250-2258

Clarke WA, Chatelut E, Fotoohi AK, Larson RA, Martin JH, Mathijssen RHJ, Salamone SJ Therapeutic drug monitoring in oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology consensus guidelines for imatinib therapy. Eur J Cancer 2021 157: 428-440 (doi: 10.1016/j.ejca.2021.08.033)

de Man FM, van Eerden RAG, van Doorn GM, Oomen-de Hoop E, Koolen SLW, Olieman JF, de Bruijn P, Veraart JN, van Halteren HK, Sandberg Y, Moelker A, IJzermans JNM, Lolkema MP, van Gelder T, Dollé MET, de Bruin RWF, Mathijssen RHJ. Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients. Clin Pharmacol Ther. 2021 109: 1304-1313 (doi: 10.1002/cpt.2094)

Donnette M, Hamimed M, Ciccolini J, Berda-Haddad Y, Kaspi E, Venton G, Lacarelle B, Costello R, Ouafik L, Farnault L, Fanciullino R. Pharmacokinetics and pharmacogenetics of liposomal cytarabine in AML patients treated with CPX-351. J Control Release 2021 338: 244-252

Ferrer F, Chauvin J, DeVictor B, Lacarelle B, Deville JL, Ciccolini J. Clinical-Based vs. Model-Based Adaptive Dosing Strategy: Retrospective Comparison in Real-World mRCC Patients Treated with Sunitinib. Pharmaceuticals 2021 14(6): 494

Gallais F, Ysebaert L, Despas F, De BS, Oberic L, Allal B, Chatelut E, White-Koning M: Population PK-PD Modeling of Circulating Lymphocyte Dynamics in Chronic Lymphocytic Leukemia Patients Under Ibrutinib Treatment. Clin Pharmacol Ther. 2021 110: 220-228.

Gota V, Nookala M, Bonda A, Karanam A, Shriyan B, Kembhavi Y, Gurjar M, Patil A, Singh A, Goyal N, Gupta S. Effect of body mass index on pharmacokinetics of paclitaxel in patients with early breast cancer. Cancer Med. 2021 10: 3068-3076 (https://doi.org/10.1002/cam4.3865)

Groenland SL, Verheijen RB, Joerger M, Mathijssen RHJ, Sparreboom A, Beijnen JH, Beumer JH, Steeghs N, Huitema ADR. Precision Dosing of Targeted Therapies is Ready for Prime Time. Clin Cancer Res. 2021 Sep 21 (https://doi: 10.1158/1078-0432.CCR-20-4555)

Hilaire MR, Gill RV, Courtney JB, Baburina I, Gardiner J, Milone MC, Shaw LM, Meng QH, Salamone SJ Evaluation of a Nanoparticle-Based Busulfan Immunoassay for Rapid Analysis on Routine Clinical Analyzers., Ther Drug Monit. 2021 (In press) (doi: 10.1097/FTD.0000000000000883)

Hurkmans DP, Sassen SDT, de Joode K, Putter L, Basak EA, Wijkhuijs AJM, Joerger M, Debets R, Koch BCP, Van der Leest CH, Schreurs MWJ, van der Veldt AAM, Aerts JGJV, Mathijssen RHJ, Koolen SLW. J Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors. Immunother Cancer 2021 9: e002344 (https://doi: 10.1136/jitc-2021-002344)

Hussaarts KGAM, van Doorn L, Bins S, Sprengers D, de Bruijn P, van Leeuwen RWF, Koolen SLW, van Gelder T, Mathijssen RHJ. Combining Sorafenib and Immunosuppression in Liver Transplant Recipients with Hepatocellular Carcinoma. Pharmaceuticals 2021 14:46 (doi: 10.3390/ph14010046)

Isberner N, Kraus S, Grigoleit GU, Aghai F, Kurlbaum M, Zimmermann S, Klinker H, Scherf-Clavel O. Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice-a prospective single-center trial. Cancer Chemother Pharmacol 2021 88: 973-983 (https://doi.org/10.1007/s00280-021-04351-w)

Le Louedec F, Gallais F, Thomas F, White-Koning M, Allal B, Protin C, Ysebaert L, Chatelut E, Puisset F: Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure: Joint Analyses with Metabolite Data. Pharmaceuticals 2021: 14 (doi: 10.3390/ph14020162)

Le Louedec F, Puisset F, Thomas F, Chatelut E, White-Koning M: Easy and reliable maximum a posteriori Bayesian estimation of pharmacokinetic parameters with the open-source R package mapbayr. CPT Pharmacometrics Syst Pharmacol 2021 10: 1208-1220.

Lurvink RJ, Tajzai R, Rovers KP, Wassenaar ECE, Moes DAR, Pluimakers G, Boerma D, Burger JWA, Nienhuijs SW, de Hingh IHJT, Deenen MJ. Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial. Ann Surg Oncol. 2021 28: 265-272 (doi: 10.1245/s10434-020-08743-9)

Ma Y, Lin Q, Yang Y, Liang W, Salamone SJ, Li Y, Lin Y, Zhao H, Zhao Y, Fang W, Huang Y, Zhang L Therapeutic Drug Monitoring of Docetaxel by Pharmacokinetics and Pharmacogenetics: A Randomized Clinical Trial of AUC-guided Dosing in Non-small Cell Lung Cancer. Clin Transl Med. 2021 11:e354 (doi: 10.1002/ctm2.354)

Mourey L, Le Louedec F, Ravaud A, Paludetto MN, Digue L, Gomez-Roca CA, Valentin T, Balardy L, Olivier P, Cabarrou B, Filleron T, Chatelut E: VOTRAGE study: Phase I dose-escalation study of pazopanib in unfit older patients. J Geriatr Oncol 2021 12: 759-764.

Mueller-Schoell A, Groenland SL, Scherf-Clavel O, van Dyk M, Huisinga W, Michelet R, Jaehde U, Steeghs N, Huitema ADR, Kloft C. Therapeutic drug monitoring of oral targeted antineoplastic drugs. Eur J Clin Pharmacol. 2021 77: 441-464 (https://doi.org/10.1007/s00228-020-03014-8)

Mueller-Schoell A, Klopp-Schulze L, Michelet R, van Dyk M, Mürdter TE, Schwab M, Joerger M, Huisinga W, Mikus G, Kloft C. Simulation-Based Assessment of the Impact of Non-Adherence on Endoxifen Target Attainment in Different Tamoxifen Dosing Strategies. Pharmaceuticals 2021 14:115 (https://doi: 10.3390/ph14020115)

Mueller-Schoell A, Michelet R, Klopp-Schulze L, van Dyk M, Mürdter TE, Schwab M, Joerger M, Huisinga W, Mikus G, Kloft C. Computational Treatment Simulations to Assess the Need for Personalized Tamoxifen Dosing in Breast Cancer Patients of Different Biogeographical Groups. Cancers 2021 13: 2432 (https://doi: 10.3390/cancers13102432)

Muth M, Ojara FW, Kloft C, Joerger M. Role of TDM-based dose adjustments for taxane anticancer drugs. Br J Clin Pharmacol 2021 87: 306-316 (https://doi: 10.1111/bcp.14678)

Nijstad AL, Barnett S, Lalmohamed A, Bérénos IM, Parke E, Carruthers V, Tweddle DA, Kong J, Zwaan M, Huitema ADR, Veal GJ. Clinical pharmacology of cytotoxic drugs in neonates and infants: providing evidence-based dosing guidance. Eur J Cancer 2021 (In press)

Padula WV, Conti RM, Beaker RV, Salamone SJ The Cost-Effectiveness of Therapeutic Drug Monitoring for the prescription drug-based Treatment of Chronic Myeloid Leukemia. J Manag Care Spec Pharm. 2021 27:1077-1085 (doi: 10.18553/jmcp.2021.27.8.1077)

Patil A, Shriyan B, Mehta P, Patil M, Gurjar M, Nookala M, Patil V, Joshi A, Noronha V, Prabhash K, Gota V. ADME gene polymorphisms do not influence the pharmacokinetics of docetaxel: Results from a population pharmacokinetic study in Indian cancer patients. Cancer Med. 2021 10: 4948-4956 (https://doi.org/10.1002/cam4.4026)

Puszkiel A, Arellano C, Vachoux C, Evrard A, Le Morvan V, Boyer JC, Robert J, Delmas C, Dalenc F, Debled M, Venat-Bouvet L, Jacot W, Dohollou N, Bernard-Marty C, Laharie-Mineur H, Filleron T, Roché H, Chatelut E, Thomas F, White-Koning M. Model-Based Quantification of Impact of Genetic Polymorphisms and Co-Medications on Pharmacokinetics of Tamoxifen and Six Metabolites in Breast Cancer. Clin Pharmacol Ther. 2021 109: 1244-1255 (https://doi-org/10.1002/cpt.2077)

Sanchez-Spitman AB, Swen JJ, Dezentjé VO, Moes DJAR, Gelderblom H, Guchelaar HJ. Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse. Sci Rep. 2021 11:415. (doi: 10.1038/s41598-020-79972-x)

van der Stoep MYEC, Bertaina A, Moes DJAR, Algeri M, Bredius RGM, Smiers FJW, Berghuis D, Buddingh EP, Mohseny AB, Guchelaar HJ, Locatelli F, Zwaveling J, Lankester AC. Impact of treosulfan exposure on early and long-term clinical outcome in pediatric allogeneic HSCT recipients: a prospective multicenter study. Transplant Cell Ther. 2021 (In press) (doi: 10.1016/j.jtct.2021.09.018)

Veal GJ, Tweddle DA, Visser J, Errington J, Buck H, Marange J, Moss J, Joseph S, Mulla H. Pharmacokinetics and safety of a novel oral liquid formulation of 13-cis retinoic acid in children with neuroblastoma: a randomised, crossover clinical trial. Cancers 2021 13: 1868 1-13 (https://doi.org/10.3390/cancers13081868)

Veerman GDM, Hussaarts KGAM, Peric R, Oomen-de Hoop E, Landa KD, van der Leest CH, Broerse SD, Rutten HB, Belderbos HNA, Steendam CMJ, Paats MS, Koolen SLW, Dingemans AC, van Gelder T, van Leeuwen RWF, Aerts JGJV, Mathijssen RHJ. Influence of Cow's Milk and Esomeprazole on the Absorption of Erlotinib: A Randomized, Crossover Pharmacokinetic Study in Lung Cancer Patients. Clin Pharmacokinet. 2021 60: 69-77 (doi: 10.1007/s40262-020-00910-1)

Yin A, Ettaieb MHT, Swen JJ, van Deun L, Kerkhofs TMA, van der Straaten RJHM, Corssmit EPM, Gelderblom H, Kerstens MN, Feelders RA, Eekhoff M, Timmers HJLM, D'Avolio A, Cusato J, Guchelaar HJ, Haak HR, Moes DJAR. Population Pharmacokinetic and Pharmacogenetic Analysis of Mitotane in Patients with Adrenocortical Carcinoma: Towards Individualized Dosing. Clin Pharmacokinet. 2021 60: 89-102 (doi: 10.1007/s40262-020-00913-y)

Zimmermann S, Kurlbaum M, Mayer S, Fassnacht M, Kroiss M, Scherf-Clavel O. Simulation-Based Interpretation of Therapeutically Monitored Cabozantinib Plasma Concentration in Advanced Adrenocortical Carcinoma with Hemodialysis. Ther Drug Monit. 2021 43:706-711 (https://doi.org/10.1097/FTD.0000000000000905)