OCULAR PHARMACOLOGY OF CHEMOTHERAPY FOR RETINOBLASTOMA.
OBJECTIVE
To review preclinical and clinical pharmacokinetic studies of the three most important chemotherapy drugs used for intraocular retinoblastoma and the contribution of the reported results to optimize treatment.


METHODS
Systemic review of pharmacokinetic studies identified by a literature search at Pubmed using the keywords carboplatin, melphalan, topotecan, intravitreal, ophthalmic artery chemosurgery, pharmacokinetics, and retinoblastoma.


RESULTS
A total of 21 studies were reviewed for assessing the preclinical and clinical pharmacokinetics of carboplatin, topotecan, and melphalan delivered by intravenous, periocular, ophthalmic artery, and intravitreal routes. Some preclinical studies were done before translation to the clinics. Others, despite encouraging preclinical data as reported for periocular topotecan did not correlate with clinical use. In addition, as was the case for melphalan after ophthalmic artery chemosurgery and despite nonfavorable preclinical information, some routes of drug delivery are clinically effective. Besides topotecan, complete knowledge of the pharmacokinetics of melphalan and carboplatin is still lacking.


CONCLUSIONS
Pharmacokinetic knowledge of chemotherapy may aid to guide retinoblastoma treatment in favor of safety and efficacy. Nonetheless, results obtained in preclinical models should be translated with care to the clinics.
*Clinical Pharmacokinetics Unit, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina; †National Scientific and Technical Research Council, CONICET, Buenos Aires, Argentina; ‡Department of Ophthalmology, VU University Medical Center, Amsterdam, the Netherlands; §Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; and ¶Service of Hematology-Oncology, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina.
Paula
P
Schaiquevich
Armida W
AW
Fabius
Jasmine H
JH
Francis
Guillermo L
GL
Chantada
David H
DH
Abramson
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007261:Infusions, Intra-Arterial; D056965:Injections, Intraocular; D008558:Melphalan / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019572:Retinal Neoplasms / Q000188:drug therapy*; D012175:Retinoblastoma / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D019772:Topotecan; D016190:Carboplatin; D008558:Melphalan