Results of treatment of retinoblastoma that has infiltrated the optic nerve, is recurrent, or has metastasized outside the eyeball.

Since the development of chemotherapy regimens for patients with retinoblastoma started in the 1950s, various agents and regimens have been employed for various kinds of patients. Chemotherapy has been employed for: (1) patients with high-risk features for metastases, such as patients with optic nerve involvement, (2) patients with orbital involvement, and (3) patients with distant metastasis. Effective systemic chemotherapeutic agents include vincristine, doxorubicin, cyclophosphamide, etoposide, cisplatin, and carboplatin, and, as well, intrathecal agents, including methotrexate, cytarabine, and corticosteroids are available. With the addition of appropriate chemotherapies to the conventional treatment modalities such as enucleation and radiotherapy, patients with advanced retinoblastoma are expected to obtain a survival benefit. Moreover, a new modality combined with autologous stem cell support allowed us to use high-dose alkylating agents such as thiotepa, melphalan, and cyclophosphamide, which resulted in better prognosis for patients with metastatic retinoblastoma. Because of the small number of patients with retinoblastoma and the diversity of the disease characteristics in individual patients, there have been no clinical trials to determine whether to recommend a particular regimen, or to identify specific criteria in patients who would benefit from chemotherapy. Well-designed prospective controlled trials are warranted to establish a standard treatment strategy for patients with extraocular retinoblastoma.