Review 10.1586/17469899.1.1.83 © 2006 Future Drugs Ltd ISSN 1746-9899 83 www.future-drugs.com Historical and modern approaches to chemotherapy for retinoblastoma Amy C Schefler, Maria Elena Jockovich, Stuart Toledano and Timothy G Murray † † Author for correspondence Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA Tel.: +1 305 326 6000 ext. 6166 Fax: +1 305 326 6147 tmurray@med.miami.edu KEYWORDS: animal models, antiangiogenesis, carboplatin, chemotherapy, etoposide, intraocular retinoblastoma, metastatic retinoblastoma, subconjunctival, vincristine Although the survival rates of retinoblastoma patients in the USA and other developed nations approach 98% and globe salvage rates have increased dramatically over time, many challenges still face both the ocular and pediatric oncologists who care for the patients with this disease. In this review, we discuss the current strategy for the utilization of chemotherapeutic agents for retinoblastoma, including intravenous delivery, subconjunctival injections and intra-arterial administration. We also review the current uses of chemotherapy for metastatic disease. The challenges and complications encountered with chemotherapeutic treatment strategies in this unique patient population will be discussed. Finally, we address the novel pharmacotherapies and delivery systems currently being explored in the laboratory that will soon be critical in clinical settings. Expert Rev. Ophthalmol. 1(1), 83–95 (2006) Retinoblastoma, the most common primary intraocular malignancy in children, has a cumulative incidence of 18,000–30,000 live births worldwide [1]. Over the past century, reported survival rates for retinoblastoma patients in the developed world have increased dramatically from 17% in 1897 to 57% in 1916, to 98% in recent years [2,3]. The improved survival rate can be attributed to earlier detection of the tumor and improved techniques for local tumor control. Along with improved survival rates in retinoblastoma patients, the rate of globe salvage has also increased over the past decade. This change can be attributed to the perfection of globe sparing treatments, including external beam radiation, laser therapy, cryotherapy, brachy- therapy and, in recent years, chemotherapy. Although Kupfer was the first to treat intra- ocular retinoblastoma with chemotherapy over 50 years ago [4], the chemotherapeutic regi- mens for this disease have been refined over time with the goal of identifying the safest and most effective drugs and combination regimens. Improved dosing schedules and adjuvant therapies to control common side effects of chemotherapeutic drugs have also contributed to enhanced globe salvage rates. Two major controversies remain unresolved among the ophthalmic oncology community regarding the chemotherapeutic management of this disease. First, disagreements remain regarding the efficacy and safety profile of single versus multiagent chemotherapy. Second, there is no universal agreement among clinicians about the ideal regimen for the use of focal adjunctive therapy, such as laser or cryo- therapy. Treatment-specific parameters for this focal therapy, such as indications, frequency, timing, power settings and direct application to the fovea or avoidance of foveal exposure, vary greatly among clinical centers. In this review, we will characterize the current use of chemo- therapeutic agents for intraocular and extra- ocular retinoblastoma and explore these con- troversies. Cutting-edge therapies and future directions in this field will also be addressed. Classification of retinoblastoma The staging of retinoblastoma is currently an area of heated controversy among clinicians [5]. The Reese–Ellsworth classifica- tion for intraocular retinoblastoma (BOX 1), developed in the 1960s, has been used almost CONTENTS Classification of retinoblastoma History of the use of chemotherapy for intraocular retinoblastoma Current use of chemotherapy for intraocular retinoblastoma Use of chemotherapy in the treatment of extraocular & metastatic disease Complications & challenges in the use of chemotherapy Expert commentary Five-year view Key issues References Affiliations