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G. L. Chantada, A. Montero Carcaboso, A. Fandiño, E. Lagomarsino, M. Guitter, A. Rose, J. Manzitti, G. Bramuglia, D. H. Abramson; A Phase I Study of PeriocularTopotecan (Pot) in Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2016.
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To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of POT in children with relapsed-resistant retinoblastoma.
Phase I dose-escalating study of POT (1 mg/ml) in patients with relapsed-resistant intraocular retinoblastoma facing imminent enucleation. Dose-limiting toxicity (DLT) was defined as ocular/visual toxicity grade 3 or greater and grade 4 or greater systemic toxicity. NCI’s CTCAE v3.0 were used to assess toxicity. Starting dose was 0,5 mg with intra-patient escalation at a rate of 0.5 mg/cycle according to toxicity up to a maximum dose of 2 mg. No further escalation was attempted because of the presumed impossibility of delivering more than 2 cc to the orbit. Plasmatic levels of topotecan were measured by HPLC. Two courses separated by 2 weeks were scheduled.
5 patients (7 eyes) received a total of 14 applications of POT. Only mild orbital edema occurred and grade 1 vomiting developed in the first patient that was controlled with ondansetron for the following courses. No other significant toxicity occurred and the maximum tolerated dose was reached at the target dose of 2 mg (n= 5 eyes). Topotecan was detected in plasma at low levels with direct correlation to dose. Even though the study was not designed to assess response, we were able to observe that one eye had a partial response, 4 had stable disease and 1 had progressive disease (one eye is still on treatment) after the second cycle.
DLT was not reached. POT (2mg) is a safe treatment option for retinoblastoma and its activity should be explored in phase 2-3 studies.
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