Level of recommendation |
Arguments of the level recommendation |
Essential |
Clinical care directly depends on TDM TDM is mentioned in governmental drug |
Strongly recommended |
Randomized trials show that TDM is associated with improvement in terms of efficacy or toxicity Pharmacoeconomic studies show interest of TDM |
Recommended |
Nonrandomized trials show that TDM is associated with improvement in terms |
Potentially useful |
Drug is associated with pharmacokinetic variability and relationships between |
Needed to be assessed |
Drug is associated with pharmacokinetic variability but relationships between |
The aim of the present article is to evaluate the usefulness of TDM in somes anti cancer drugs and to discusses their current applications and also justify their level of evidence
Table 1: The levels of evidence for therapeutic pharmacological monitoring according to the definition of the TDM group of the French Society of Pharmacology and Therapeutics
Deseases |
Doses |
Regimen |
Modalities of administration |
Pharmaco |
Lower limit of efficacy |
Upper limit of efficacy |
Pharmacodynamics relationships |
Level of evidence for |
References |
TDM |
|||||||||
Platinium salt |
|
||||||||
Cisplatin in adult |
|
||||||||
ovarian or testicular carcinoma |
80-100mg/m2 |
cisplatin |
Continous infusion over 120h |
Cmax |
1.95µg/ml |
- |
Nephrotoxicity |
Limited |
(Salas et al;2006) |
Recommendation |
|||||||||
Carboplatin in adult |
|
||||||||
ovarian carcinoma of epithelial origin |
40-1000mg/m2 |
carboplatin |
120 h with dose adjustment |
|
5 |
7 |
Thrombocytopenia, Ieukopenia |
potentially useful |
(Jodrell et al ;1992) |
small cell lung carcinoma. |
at 24 h |
AUC |
mg.min/mL |
mg.min/mL |
|||||
Oxaliplatin in adult |
|
||||||||
mCRC |
85 - 130 mg/m2 |
oxaliplatin |
2 -6 h |
Clerance < 30 mL / min |
- |
- |
Nephrotoxicity |
potentially useful |
(Gori et al ;2014) |
Cancer colon |
Dose reduced from 30% to 50% |
Hematopoetic toxicity |
|||||||
5- Fluouracil |
|
||||||||
|
1.5 |
|
|
|
20 |
24 |
Leukopenia, thrombocytopenia |
|
|
mCRC |
g/m2 |
5- FU |
|
AUC0-8h |
mg/min/ml |
mg/min/ml |
Toxicity:mucositis, diarrhea,leukopenia,anemia |
|
(Lee et al ; 2016 |
|
|
|
8h |
Cmin |
2500ng/ml |
3000ng/ml |
|
Strongly recommended |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CRC |
1.3 |
5-FU +Leucovorin |
|
AUC0-8h |
16 |
24 |
|
|
(Gamelin et al ;1999) |
g/m2 |
8h |
Cmin |
mg/min/ml |
mg/min/ml |
|
|
|||
|
|
|
2000ng/ml |
3000ng/ml |
|
|
|||
Head and Neck |
1g/m2 |
5-FU+ oxaliplatin (130mg/m2)+ folonic acid |
Over 46h |
|
20 |
30 |
|
|
(Goirand et al ;2018) |
AUC0-5days |
mg/min/ml |
mg/min/ml |
|
|
Table 2: Evidence level of TDM for platinum compounds and 5-FU as a function of cancer type
|
Methotrexate level (µmol/l) |
|||||
T/Methotrexate |
< 0.2 |
0.2 – 0.5 |
0.5-1 |
1 - 5 |
5 - 10 |
> 10 |
H 36 |
- |
25 mg x 4 |
25mg x 4 |
25mg x 4 |
25mg x 4 |
25mg x 4 |
H 48 |
- |
25 mg x 4 |
25mg x 4 |
25mg x 4 |
25mg x 4 |
100 mg x 4 |
H 72 |
- |
25mg x 4 |
25mg x 4 |
100 mg x 4 |
200 mg x 4 |
400 mg x 4 |
H 96 |
- |
25mg x 4 |
100 mg x 4 |
200 mg x 4 |
400 mg x 4 |
400 mg x 4 |
>H 96 |
- |
100mg x 4 |
200 mg x 4 |
400 mg x 4 |
400 mg x 4 |
400 mg x 4 |
T : time since The start of MTX infusion, MTX : Methotrexate level in µmol/l
Table 3: Adjustment of folinic acid doses level and administration time of Methotrexate in LAL adults patients according to therapeutic recommendation « GRALL » 2005
Tables at a glance