A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma. Initial results Journal Article


Authors: Abramson, D. H.; Dunkel, I. J.; Brodie, S. E.; Kim, J. W.; Gobin, Y. P.
Article Title: A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma. Initial results
Abstract: Objective: To develop a technique that would allow us to cannulate repeatedly the ophthalmic artery of young children with advanced retinoblastoma, to find a dose of melphalan that would be tolerable and tumoricidal for retinoblastoma when given intraarterially, and to study the local ocular and systemic side effects of intraarterial melphalan in these children. Design: Phase I/II clinical trial. Participants: Ten children with advanced retinoblastoma (Reese-Ellsworth V) eyes who were indicated for enucleation were entered into an institutional review board-approved protocol of ophthalmic artery infusion of melphalan to avoid enucleation. Methods: Cannulation of the ophthalmic artery was performed by a femoral artery approach using microcatheters while the children were under anesthesia and anticoagulated. Chemotherapy (melphalan) was infused into the artery over a 30-minute period. Main Outcome Measures: Ophthalmic examinations, retinal photography, and electroretinograms were used to document local toxicity, whereas physical examinations and complete blood counts were used to measure systemic toxicity. Results: The ophthalmic arteries were successfully cannulated in 9 cases (total, 27 times), as many as 6 times in 1 patient. Dramatic regression of tumors, vitreous seeds, and subretinal seeds were seen in each case. No severe systemic side effects (sepsis, anemia, neutropenia, fever, or death) occurred. No transfusions were required (red cells or platelets). Three patients developed conjunctival and lid edema that resolved without treatment. There was no toxicity to the cornea, anterior segment, pupil, or motility. One (previously irradiated) eye developed retinal ischemia; another eye had no toxicity after intraarterial chemotherapy but did develop a radiationlike retinopathy after brachytherapy. Vision stabilized or improved in all but 1 patient after treatment. Electroretinograms were generally poor (advanced eyes were treated), but in 2 cases, the electroretinogram improved after treatment (and resolution of a retinal detachment). Seven eyes avoided enucleation. Two intraarterially treated eyes were enucleated, with no viable tumors identified pathologically. Conclusions: We developed a technique of direct ophthalmic artery infusion of melphalan for children with retinoblastoma. The technique had minimal systemic side effects (one patient had grade 3 neutropenia) and minimal local toxicity. Among the first 9 cases treated with this technique, 7 eyes destined to be enucleated were salvaged. © 2008 American Academy of Ophthalmology.
Keywords: cancer chemotherapy; treatment outcome; child, preschool; clinical trial; drug tolerability; neutropenia; advanced cancer; cancer radiotherapy; follow-up studies; phase 2 clinical trial; anemia; melphalan; antineoplastic activity; continuous infusion; retinoblastoma; tumor regression; pathology; retinal neoplasms; radiation injury; childhood cancer; drug fever; drug fatality; infant; stroke; antineoplastic agents, alkylating; catheterization; intraarterial drug administration; infusions, intra-arterial; brachytherapy; sepsis; electroretinography; artery catheterization; enucleation; eyelid edema; ophthalmic artery; retina detachment; retinopathy; vision; anticoagulation; physical examination; blood cell count; phase 1 clinical trial; erythrocyte transfusion; photography; dose calculation; eye toxicity; thrombocyte transfusion; eye examination; anesthesia; drug indication; catheter; electroretinogram; eye photography; femoral artery; hyperemia; vitreous body; chemosis; cornea disease; retina ischemia
Journal Title: Ophthalmology
Volume: 115
Issue: 8
ISSN: 0161-6420
Publisher: Elsevier Science, Inc.  
Date Published: 2008-08-01
Start Page: 1398
End Page: 1404.e1
Language: English
DOI: 10.1016/j.ophtha.2007.12.014
PUBMED: 18342944
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 44" - "Export Date: 17 November 2011" - "CODEN: OPHTD" - "Source: Scopus"
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  1. Ira J Dunkel
    371 Dunkel
  2. Jonathan Wano Kim
    6 Kim
  3. David H Abramson
    389 Abramson
  4. Scott Brodie
    38 Brodie