High dose methotrexate in adult patients with osteosarcoma: Clinical and pharmacokinetic results

Figures & data

Table I.  Patient characteristics.

Number of patients	31
Sex	20 m/11 f
Median age	27.7 ys (range 16–39)
Primary tumor site	femur 16
	humerus 6
	tibia 4
	spine 2
	maxilla 2
	pelvis 1
Prior surgery	4
Surgery after CT	27
Disease extension	loco regional 20
	recurrent 3
	metastatic 8
Grade of necrosis	good responders (>90%) 13 pt
	poor responders (<90%) 14 pt
	unknown 4 pt

Figure 1. HDMTX concentration-time profile (median-range).

Table IIa.  NCA results.

		median	range
dose	µmol	39 727.1	32 102.7–52 811.1
Cmax	µM	1 149.5	692–2 200
AUCtot	µmol*h/l	6 955.06	3 477.1–12 681.2
Kel	1/h	0.19	0.09–0.29
t½	h	4.02	2.37–11.42
MRT	h	4.72	3.47–8.27
Cltot	l/h	5.95	3.03–11.00
Vz	l	36.52	16.5–140.0
Vss	l	27.27	12.6–44.6

dose: MTX median dose/cycle; C_max: maximum concentration; AUC_tot: total area under concentration-time curve; K_el: elimination rate constant; t^1/2: elimination half-life; MRT: mean residence time; Cl_tot: total clearance; V_z: volume of distribution of the late elimination phase; V_ss: volume of distribution at the steady state.

Table IIb.  Population pk results.

Population pk two-compartment model equations
V = − 5.258 + 0.052*ALT + 0.087* height + 0.196*weight
Kel=0.286 − 0.001*AST-0.162*creatinine + 0.009*hemoglobin
K12=0.011
K21=0.070

V: volume of distribution; K_el: elimination rate constant; K₁₂: transfer rate constant from central to tissue compartment; K₂₁: transfer rate constant from tissue to central compartment; ALT/AST: serum transaminases.

Figure 2. Overall survival curve (Kaplan-Meier).