The knowledge of radiation-related second cancers has been one of themain stimuli for the development of alternative strategies in the managementand treatment of patients with RB. Worldwide, systemic and local chemotherapieshave been used since the mid-1990s in the hope that cures for RB may be attainedwithout an increased risk of second cancers.19- 22 Chemotherapyalone seems to rarely cure intraocular RB; however, when combined with focaltechniques (photocoagulation, transpupillary thermotherapy, cryotherapy, andradioactive plaques), it has proved to be a useful adjunct, often obviatingthe need for EBT. The success of the chemotherapy plus focal techniques approach,however, seems related to the extent of the intraocular disease. For Reese-Ellsworth(RE) groups I, II, and III, radiation can usually be avoided. For eyes inwhich the tumors are larger, such as RE groups IV (multiple tumors, some >10disc diameters, and/or lesions extending anteriorly to the ora serrata) andV (massive tumors involving more than half of the retina, with or withoutseeding), success rates are much lower. These children require multidrug chemotherapy,usually for 6 to 9 months, with a significant incidence of systemic toxicity,including anemia, anorexia, leukopenia, myelosuppression, neurotoxicity, neutropenia,secondary infections, and optic atrophy.23 Theliterature20,21,24 suggeststhat most of these eyes are not cured with chemotherapy alone and may stillreceive EBT and/or undergo enucleation. The impact of a chemotherapeutic approachon second cancers is not known, but recent evidence25- 29 suggeststhat acute myelocytic leukemia may be induced by etoposide.