**Abstract**

The treatment of children with retinoblastoma (RB) has evolved from primarily enucleation of the eye(s) to highly selective methods of chemotherapy administration and approach. Indulgent and comprehensive understanding of the multitude of factors including accurate classification and grading of disease, timing and response to therapy, when to consolidate with local methods of therapy, combination regimens to control systemic disease and prevent relapse while minimizing risk of secondary cancers are crucial factors in the management of children with retinoblastoma. Chemotherapy was introduced in the 1950s and has become an integral component in management of RB. Methods of administration range from systemic to locally directed therapy including; intravitreal, periocular and intraarterial chemotherapy. This chapter is intended to discuss the evolution and current chemotherapeutic agents with various routes of administration. The indications, adverse occurrences, short- and long-term complications of both local and systemic treatments will be elucidated.

**Keywords:** chemotherapy, retinoblastoma, metastasis, intravenous, intra-arterial, intravitreal, periocular, vitreous seeds

## **1. Introduction**

The treatment of retinoblastoma is challenging, as the governing objectives are preserving life, protecting from pineoblastoma, decreasing the lifetime incidence of secondary tumors and salvaging useful vision without exposing the patient to significant and serious side effects that may endanger the patient's survival and quality of life. The treatment of retinoblastoma evolved steadily during the past decades, and multiple modalities of treatment were introduced including chemotherapy. At one time, chemotherapy was used mainly to manage metastatic retinoblastoma, but later the interest of scientists and clinicians shifted to the use of this treatment strategy for non-metastatic retinoblastoma. As the interest of experts grew and the demand for better overall outcome increased, multiple interesting treatment strategies were developed and refined. Now, four main routes of administration of chemotherapy are present, and these are: intravenous chemotherapy (IVC), intraarterial chemotherapy (IAC), intravitreal chemotherapy (IVitC) and periocular chemotherapy (POC).

Today, chemotherapy is regarded as one of the indispensable pillars of treatment of retinoblastoma. In fact, retinoblastoma is currently one of the most commonly curable childhood malignant tumors universally. In developed countries, the rates of expected survival exceed 95% whereas the rates in developing countries are

lower due to the limited healthcare resources [1]. The different chemotherapy treatment strategies outlined above will be discussed thoroughly in the upcoming sections.
