April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Topotecan pharmacokinetics and safety after super-selective ophthalmic artery infusion concomitant to melphalan in children with retinoblastoma
Author Affiliations & Notes
  • Paula Juliana Taich
    Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina
  • Alejandro Ceciliano
    Maternidad Suizo Argentina, Argentina, Buenos Aires, Argentina
  • Emiliano Buitrago
    Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina
  • Francisco Villasante
    Maternidad Suizo Argentina, Argentina, Buenos Aires, Argentina
  • Claudia Sampor
    Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina
  • Gabriel Mato
    Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina
  • Guillermo Luis Chantada
    Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina
  • Paula Schaiquevich
    Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina
  • Footnotes
    Commercial Relationships Paula Taich, None; Alejandro Ceciliano, None; Emiliano Buitrago, None; Francisco Villasante, None; Claudia Sampor, None; Gabriel Mato, None; Guillermo Chantada, None; Paula Schaiquevich, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3071. doi:
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      Paula Juliana Taich, Alejandro Ceciliano, Emiliano Buitrago, Francisco Villasante, Claudia Sampor, Gabriel Mato, Guillermo Luis Chantada, Paula Schaiquevich; Topotecan pharmacokinetics and safety after super-selective ophthalmic artery infusion concomitant to melphalan in children with retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3071.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

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 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 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%).

Keywords: 703 retinoblastoma • 763 vitreous  
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