Intraocular carboplatin concentrations following intravenous administration for human intraocular retinoblastoma.
Previous studies of the penetration of carboplatin into the vitreous have depended on unaffected animals or on animal models for other cancers. The objective of this study was to determine the intraocular levels of carboplatin following intravenous administration of carboplatin in the treatment of human intraocular retinoblastoma. Eight patients with bilateral intraocular retinoblastoma were treated in a consistent fashion with intravenous carboplatin. One additional patient was similarly treated, but enucleated one month later. Samples were taken from those nine eyes after enucleation one to two hours after the administration of 18.7 mg/kg (560 mg/m( 2) for patients more than 12 kg) of intravenous carboplatin, and carboplatin concentrations in the aqueous and vitreous were then measured by atomic absorption spectrometry. The mean concentration measured in the aqueous was 5.13 microg/ml and in the vitreous 4.05 microg/ml, and vitreal concentrations were an average of 80% of aqueous concentrations. In one patient, a vitreous concentration of carboplatin was detected after an interval of one month that was 10% of the levels found in the samples enucleated one hour post-administration. These concentrations are much higher than previous animal studies would predict, and are similar to levels measured in unaffected animals when the drug is given after the use of cryotherapy. The concentration also approaches levels previously shown to be toxic to the retina. This elevation in carboplatin concentration may be due to disruption of the blood-vitreous barrier by active tumor.
Abramson
D H
DH
New York Hopsital-Cornell University Medical Center, New York, NY, USA.
Frank
C M
CM
Chantada
G L
GL
de Totah
A B
AB
de Pifano
I T
IT
Ramírez
G T
GT
Gomez
R T
RT
Fandino
A T
AT
Tran
H T
HT
Madden
T J
TJ
Dunkel
I J
IJ
D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001082:Aqueous Humor / Q000378:metabolism; D016190:Carboplatin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005123:Eye / Q000378:metabolism*; D015353:Eye Enucleation; D006801:Humans; D007275:Injections, Intravenous; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D012175:Retinoblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D014822:Vitreous Body / Q000378:metabolism
D000970:Antineoplastic Agents; D016190:Carboplatin