INVESTIGADORES
CHANTADA Guillermo Luis
congresos y reuniones científicas
Título:
Topotecan pharmacokinetics and safety after super-selective
Autor/es:
PAULA J. TAICH1, ALEJANDRO CECILIANO2, EMILIANO BUITRAGO1, FRANCISCO, CHANTADA G, SCHAIQUEVICH P
Reunión:
Congreso; ARVO Annual Meeting; 2014
Resumen:
Purpose: To characterize topotecan pharmacokinetics and safety after
super-selective ophthalmic artery infusion (SSOAI) in combination
with melphalan in children with retinoblastoma.
Methods: Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
h after finishing SSOAI. Topotecan was quantified by HPLC and the
pharmacokinetics was characterized using a nonlinear mixed effects
modeling approach. After each chemotherapy cycle, hematological
toxicities were graded according to international criteria. Patients
received both drugs at no predetermined order (sequence effect).
Results: A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
concomitant to melphalan in 39 cycles. The median (range) age and
A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
weight at the first cycle was 1.6 years (0.75-7.4) and 11.6kg (7.9-
30), respectively. Topotecan pharmacokinetics was best described
by a 2-compartment model with an additive residual error model
according to the limit of quantitation (5ng/ml). Topotecan mean (s.e)
pharmacokinetic parameters calculated included clearance: 0.67 L/h/
kg (0.07); volume of distribution of the central compartment: 0.53 L/
kg (0.09), intercompartmental clearance: 2.86 L/h/kg (0.34); volume
of distribution of the peripheral compartment: 0.72 L/kg (0.07) and
a median (range) systemic exposure corrected by dose of (AUC/D):
super-selective ophthalmic artery infusion (SSOAI) in combinationsuper-selective ophthalmic artery infusion (SSOAI) in combination
with melphalan in children with retinoblastoma.
super-selective ophthalmic artery infusion (SSOAI) in combination
with melphalan in children with retinoblastoma.
Methods: Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
h after finishing SSOAI. Topotecan was quantified by HPLC and the
pharmacokinetics was characterized using a nonlinear mixed effects
modeling approach. After each chemotherapy cycle, hematological
toxicities were graded according to international criteria. Patients
received both drugs at no predetermined order (sequence effect).
Results: A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
concomitant to melphalan in 39 cycles. The median (range) age and
A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
weight at the first cycle was 1.6 years (0.75-7.4) and 11.6kg (7.9-
30), respectively. Topotecan pharmacokinetics was best described
by a 2-compartment model with an additive residual error model
according to the limit of quantitation (5ng/ml). Topotecan mean (s.e)
pharmacokinetic parameters calculated included clearance: 0.67 L/h/
kg (0.07); volume of distribution of the central compartment: 0.53 L/
kg (0.09), intercompartmental clearance: 2.86 L/h/kg (0.34); volume
of distribution of the peripheral compartment: 0.72 L/kg (0.07) and
a median (range) systemic exposure corrected by dose of (AUC/D):
super-selective ophthalmic artery infusion (SSOAI) in combinationsuper-selective ophthalmic artery infusion (SSOAI) in combination
with melphalan in children with retinoblastoma.
To characterize topotecan pharmacokinetics and safety after
super-selective ophthalmic artery infusion (SSOAI) in combination
with melphalan in children with retinoblastoma.
Methods: Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
h after finishing SSOAI. Topotecan was quantified by HPLC and the
pharmacokinetics was characterized using a nonlinear mixed effects
modeling approach. After each chemotherapy cycle, hematological
toxicities were graded according to international criteria. Patients
received both drugs at no predetermined order (sequence effect).
Results: A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
concomitant to melphalan in 39 cycles. The median (range) age and
A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
weight at the first cycle was 1.6 years (0.75-7.4) and 11.6kg (7.9-
30), respectively. Topotecan pharmacokinetics was best described
by a 2-compartment model with an additive residual error model
according to the limit of quantitation (5ng/ml). Topotecan mean (s.e)
pharmacokinetic parameters calculated included clearance: 0.67 L/h/
kg (0.07); volume of distribution of the central compartment: 0.53 L/
kg (0.09), intercompartmental clearance: 2.86 L/h/kg (0.34); volume
of distribution of the peripheral compartment: 0.72 L/kg (0.07) and
a median (range) systemic exposure corrected by dose of (AUC/D):
super-selective ophthalmic artery infusion (SSOAI) in combinationsuper-selective ophthalmic artery infusion (SSOAI) in combination
with melphalan in children with retinoblastoma.
Methods: Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
Topotecan SSOAI concomitant to melphalan was offered
to children with retinoblastoma between October 2011 and July
2013. The SSOAI therapy was performed according to published
guidelines. Consenting patients received SSOAI topotecan (0.5-1
mg) concomitant to melphalan (3-7 mg) in unilateral administration.
Blood samples were collected from a peripheral access before
starting and at the end of the infusion of each drug and 0.5, 1, 2 and 3
h after finishing SSOAI. Topotecan was quantified by HPLC and the
pharmacokinetics was characterized using a nonlinear mixed effects
modeling approach. After each chemotherapy cycle, hematological
toxicities were graded according to international criteria. Patients
received both drugs at no predetermined order (sequence effect).
Results: A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
concomitant to melphalan in 39 cycles. The median (range) age and
A total of 21 patients received SSOAI topotecan
concomitant to melphalan in 39 cycles. The median (range) age and
weight at the first cycle was 1.6 years (0.75-7.4) and 11.6kg (7.9-
30), respectively. Topotecan pharmacokinetics was best described
by a 2-compartment model with an additive residual error model
according to the limit of quantitation (5ng/ml). Topotecan mean (s.e)
pharmacokinetic parameters calculated included clearance: 0.67 L/h/
kg (0.07); volume of distribution of the central compartment: 0.53 L/
kg (0.09), intercompartmental clearance: 2.86 L/h/kg (0.34); volume
of distribution of the peripheral compartment: 0.72 L/kg (0.07) and
a median (range) systemic exposure corrected by dose of (AUC/D):
95.5 (ng*h/ml)/mg (34.5-237.9). Adverse events included 5 grade
3/4 neutropenia with an incidence of 12.8 % of myelosupression. The
sequence of drug administration was not statistically associated with
topotecan clearance (p>0.05).
Conclusions: The present data are in agreement with topotecan
pharmacokinetics after endovenous administration previously
reported in children. Topotecan systemic exposure was low and is
in correspondence with the low incidence of hematological toxicity
(12.8%).
pharmacokinetics after endovenous administration previously
reported in children. Topotecan systemic exposure was low and is
in correspondence with the low incidence of hematological toxicity
(12.8%).
The present data are in agreement with topotecan
pharmacokinetics after endovenous administration previously
reported in children. Topotecan systemic exposure was low and is
in correspondence with the low incidence of hematological toxicity
(12.8%).