Level of recommendation	Arguments of the level recommendation
Essential	Clinical care directly depends on TDM TDM is mentioned in governmental drug approval
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 of efficacy or toxicity
Potentially useful	Drug is associated with pharmacokinetic variability and relationships between exposure and efficacy or toxicity are observed
Needed to be assessed	Drug is associated with pharmacokinetic variability but relationships between exposure and efficacy or toxicity are lackingTherapeutic range is often large

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 kinetics (PK)	Lower limit of efficacy	Upper limit of efficacy	Pharmacodynamics relationships	Level of evidence for	References
Deseases	Doses	Regimen	Modalities of administration	Pharmaco kinetics (PK)	Lower limit of efficacy	Upper limit of efficacy	Pharmacodynamics relationships	TDM	References
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)
ovarian or testicular carcinoma	80-100mg/m2	cisplatin	Continous infusion over 120h	Cmax	1.95µg/ml	-	Nephrotoxicity	Recommendation	(Salas et al;2006)
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.	40-1000mg/m2	carboplatin	at 24 h	AUC	mg.min/mL	mg.min/mL	Thrombocytopenia, Ieukopenia	potentially useful	(Jodrell et al ;1992)
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	85 - 130 mg/m2	oxaliplatin	2 -6 h	Dose reduced from 30% to 50%	-	-	Hematopoetic toxicity	potentially useful	(Gori et al ;2014)
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)
Head and Neck	1g/m2	5-FU+ oxaliplatin (130mg/m2)+ folonic acid	Over 46h	AUC0-5days	mg/min/ml	mg/min/ml			(Goirand et al ;2018)

	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

Tables at a glance