CHEMOTHERAPY PLUS LOCAL TREATMENT IN THE MANAGEMENT OF INTRAOCULAR RETINOBLASTOMA

Objective: To describe platinum-based chemotherapy combined with local treatment modalities as an alternative to external beam radiotherapy for intraocular retinoblastoma. Design: Platinum levels st ere measure d by atomic absorption analysis in the tumors of 2 patients with retin oblastoma given carboplatin 5 or 2.5 hours before enucleation. Platinu m levels in heated vs nonheated Greene melanoma tumors in rabbits were compared. A retrospective review of 172 affected eyes in 136 consecut ive patients treated for retinoblastoma between January 1990 and Decem ber 1945 was performed. From 1990 to 1992, all treatable eyes initiall y received systemic carboplatin, 560 mg/m(2), followed by 15 to 30 min utes of continuous diode laser hyperthermia (thermochemotherapy). Sinc e 1992, larger tumors were treated initially with 3 monthly cycles of carboplatin, etoposide, and vincristine sulfate to reduce tumor volume (chemoreduction) followed by sequential aggressive local therapy (SAL C) during examinations under anesthesia every 2 to 3 weeks. Outcome Me asure: Treatment success was defined as eradication of tumor without e nucleation or external beam radiotherapy. Results: Significant therape utic platinum levels were measured in the human tumors 2.5 and 5 hours after carboplatin administration. Increasing the temperature by 9 deg rees C for 15 minutes doubled platinum levers in the rabbit model.Of t he 38 eyes with Reese-Ellswosth group 1 through 5b rumors that were tr eated primarily with thermochemotherapy, all 24 eyes with group 1 and 2 tumors were treated successfully and two of the 4 eyes with group 3 tumors and all 10 eyes with group 5b rumors were treated unsuccessfull y. Chemoreduction plus SALT was the primary treatment in 35 eyes and w as successful in all 10 eyes with group, 1 through 4 tumors and unsucc essful in all 7 eyes with extensive subretinal seeding and all 18 eyes with group 5b tumors with vitreous seeding. Seventy patients received carboplatin or carboplatin, vincristine, and etoposide, with myelosup pression, occasionally associated with bacteremia, being the main side effect. Transfusions were required in 15% of patients. Radiation reti nopathy occurred in all 6 eyes treated with iodine 125 plaques. Conclu sions: Thermochemotherapy is successful primary treatment, for Reese-E llsworth group 1 and 2 retinoblastomas. For larger tumors in the absen ce of vitreous or Extensive subretinal seeding, 3 cycles of chemoreduc tion followed by SALT eradicates residual viable tumor. Chemoreduction plus SALT was not successful in eyes with diffuse vitreous or extensi ve subretinal seeding. Prior chemotherapy increases the risk for radia tion retinopathy following I-125 plaque therapy. External beam radioth erapy can safely be avoided in the primary treatment of Reese-Ellswort h groups 1 through 4 nondispersed retinoblastoma.