EFFECT OF CHEMOTHERAPY ON INTRAOCULAR RETINOBLASTOMA

Background: Radiation preserves vision in the retained eyes of childre n with bilateral retinoblastoma with germline RB1 mutations but signif icantly increases their risk of second cancers. Although less mutageni c than radiation, chemotherapy alone seldom controls these tumors perm anently. Methods: We explored the use of chemotherapy to preserve visi on without radiation or avoid second enucleations after radiation fail ure. In 10 patients with tumors in the remaining eye after enucleation of the more severely involved first eye and 1 patient with tumors in both eyes, short courses of chemotherapy were used to shrink large or posteriorly placed tumors before ablation with focal cryotherapy and l aser therapy. Concurrent chemotherapy was used in another 5 patients w ith large tumors or vitreous seeds undergoing radiation. The multidrug -resistance P-glycoprotein was tested in 20 resected tumors, 15 at dia gnosis and 5 after failure. Results: Permanent control of tumor by che motherapy and focal therapy occurred in 2/4 radiation failures and 4/7 patients treated at onset (median duration, 5.2(+) years). Additional ly, concurrent chemotherapy may have contributed to long-term. respons es in 2/5 patients radiated. Relapses in 7/8 patients occurred before 1 year. P-glycoprotein was overexpressed in all 5 tumors after failure but only 1/15 tumors pretreatment. Conclusion: Chemotherapy consolida ted by focal therapy produces long-term responses and allows radiation or second enucleations to be avoided in some cases of bilateral retin oblastoma. The frequency of P-glycoprotein overexpression in tumors th at Failed treatment suggests that multidrug-resistant tumor cells may be limiting the effectiveness of chemotherapy.