TY - JOUR
T1 - Therapeutic Drug Monitoring of Oral Anticancer Drugs
T2 - The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study
AU - Groenland, Stefanie L.
AU - Van Eerden, Ruben A.G.
AU - Verheijen, Remy B.
AU - Koolen, Stijn L.W.
AU - Moes, Dirk Jan A.R.
AU - Desar, Ingrid M.E.
AU - Reyners, Anna K.L.
AU - Gelderblom, Hans J.
AU - Van Erp, Nielka P.
AU - Mathijssen, Ron H.J.
AU - Huitema, Alwin D.R.
AU - Steeghs, Neeltje
N1 - Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Background: Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes. Methods: In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (Cmin) will be calculated. In cases where Cmin falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug-drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase.Discussion:Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.
AB - Background: Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes. Methods: In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (Cmin) will be calculated. In cases where Cmin falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug-drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase.Discussion:Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.
KW - individualized dosing
KW - oral anticancer drugs
KW - personalized dosing
KW - PK
KW - TDM
UR - http://www.scopus.com/inward/record.url?scp=85072773132&partnerID=8YFLogxK
U2 - 10.1097/FTD.0000000000000654
DO - 10.1097/FTD.0000000000000654
M3 - Article
C2 - 31568233
AN - SCOPUS:85072773132
SN - 0163-4356
VL - 41
SP - 561
EP - 567
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
IS - 5
ER -