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RET5: Treatment for Patients with Cancer of the Eye - Retinoblastoma

Why was this study done?

Retinoblastoma is a childhood cancer that affects the eye’s retina. Our aim is to cure the cancer, save the child’s life, and preserve as much vision as possible. New chemotherapy (medicine) drugs are needed for children with this disease. A drug called topotecan had good results for children with tumors of the brain, central nervous system, nerves and muscles. Early studies showed it might also work against retinoblastoma.

Very young patients are at risk of hearing loss if they receive the chemo drug called carboplatin, but the risk is less if the child is older than 6 months at the time of the first dose. Another chemo, etoposide, has been linked to some cases of secondary leukemia. We wanted to find out if we could delay giving carboplatin and remove etoposide while keeping survival rates high.

The study’s other goals were to:

  • Find out how many children would respond to the individualized treatments.
  • Learn how tumors in children with disease in both eyes respond to topotecan and vincristine, with a type of growth factor that helps blood cells recover after chemo.
  • Learn more about patients’ intellectual, social, and emotional development.
  • Find out if a part of the brain called the pineal gland changes in size after chemo treatment.
  • Learn more about the genetics of retinoblastoma tumors.

When was this study done?

The study opened in April 2005 and closed in November 2010.

What did the study consist of?

Treatment depends on whether the tumor affects one eye or both eyes, how advanced the tumor is within the eye (“early” vs. “advanced”), and if the tumor has spread outside the eye.

The study was divided into three groups:

  • Group A: Patients with early disease (not as advanced) or those with disease in both eyes who had one eye removed and the remaining eye had early disease got eight courses of vincristine and carboplatin. They also got focal therapies to shrink and kill the tumor(s). Focal therapies include:
    • laser therapy,
    • freezing (cryotherapy),
    • local delivery of radiation (“brachytherapy”), or
    • heat treatments that are directed at the tumor(s) while the child is asleep (under sedation).
  • Group B: Patients with advanced disease in both eyes started therapy with two cycles of vincristine and topotecan. Those with a good response continued with 9 more courses of chemo with vincristine, topotecan and carboplatin. Radiation to the eye and tissue surrounding the eye was avoided unless it was necessary to save the child’s vision.
  • Group C: Patients with advanced disease in one eye had that eye removed at diagnosis. They were then treated based on risk factors when the eye was examined under the microscope (“pathology risk factors”):
  • Those with no evidence that the tumor was invading into or outside the layers of the eye were low risk and had no more treatment.
  • Children with tumors that started to invade into the layers of the eye were considered intermediate or high risk, depending on how deeply the tumor invaded.
    • Patients with intermediate risk got four courses of vincristine, cyclophosphamide and doxorubicin. This was followed by a type of growth factor that helps blood cells recover after chemo.
    • Patients with high-risk disease got chemo with vincristine, carboplatin and etoposide alternated with vincristine, cyclophosphamide and doxorubicin for a total of 6 courses. Radiation was given if the tumor invaded into the tissues around the eye or to the end of the nerve attached to the eye (optic nerve).

What did we learn from this study?

  • The number of tumors and the size of tumors got smaller for patients in Group B after 2 courses of vincristine and topotecan. Treatment success was best in large tumors, tumors closest to the optic nerve (not in the edges or periphery of the eye), and in patients older than 4 months at time of diagnosis.
  • Patients tolerated the chemo well, but they did have to receive transfusions of blood and platelets. This is an expected side effect, but patients and doctors must be aware of the need for this support.
  • Patients with advanced disease in 1 eye that had not spread and who had that eye removed at diagnosis could be cured with a graduated-intensity approach based on pathology.
  • Topotecan combined with vincristine, carboplatin, and aggressive focal therapies works well for children with advanced retinoblastoma. The treatments save their eyes and their vision. More than 75% of patients in this group had vision in at least 1 eye of 20/40 or better, which is good enough to get a driver’s license.
  • We found the best starting doses of topotecan for different age groups based on how their bodies actually use and break down the drug, rather than just how much the patient weighs.

What are the next research steps as a result of this study?

This was a single-institution study, and more patients should be treated with these drugs to know the long‐term success of this treatment for children with advanced disease.

The successful use of topotecan in advanced disease may be useful in early disease, which may be present in the youngest patients. This would allow the child to be older when treated with carboplatin and may reduce the risk for hearing loss.

Topotecan causes shrinkage of tumors in the retina cells, but some tumors break apart inside the eye (vitreous seeds). These seeds are quite resistant to standard chemo approaches. Chemo that is delivered directly into the eye or is targeted to kill tumor cells and not normal retina may be necessary to save more eyes.

Retinal detachment resolved in 36% of eyes after only 2 courses of therapy in patients with advanced disease. It is important to study this carefully in future patients to see if this will extend to a larger number of patients.

How does this study affect my child?

Every childhood cancer survivor should receive long-term follow-up care. Through the St. Jude After Completion of Therapy Clinic, your child will receive information and guidance for care after treatment. Please speak with your St. Jude doctor about specific guidelines that apply to your child.

For more information

Please talk with your child’s St. Jude doctor about questions or concerns you have as a result of this study.

Publications generated from this study:

Chemoreduction with Topotecan and Vincristine: Quantifying Tumor Response in Bilateral Retinoblastoma Patients. King BA, Sahr N, Sykes A, Wilson MW, Brennan RC. Pediatr Blood Cancer. 2021 Apr;68(4):e28882.

Pathologic Risk-based Adjuvant Chemotherapy for Unilateral Retinoblastoma Following Enucleation. Sullivan EM, Wilson MW, Billups CA, Wu J, Merchant TE, Brennan RC, Haik BG, Shulkin B, Free TM, Given V, Rodriguez-Galindo C, Qaddoumi I. J Pediatr Hematol Oncol. 2014 Aug;36(6):e335-40.

Topotecan and Vincristine Combination Is Effective Against Advanced Bilateral Intraocular Retinoblastoma and Has Manageable Toxicity. Qaddoumi I, Billups CA, Tagen M, Stewart CF, Wu J, Helton K, McCarville MB, Merchant TE, Brennan R, Free TM, Given V, Haik BG, Rodriguez-Galindo C, Wilson MW. Cancer. 2012 Nov 15;118(22):5663-70.

Ocular Salvage and Vision Preservation Using a Topotecan-Based Regimen for Advanced Intraocular Retinoblastoma. Brennan RC, Qaddoumi I, Mao S, Wu J, Billups CA, Stewart CF, Hoehn ME, Rodriguez-Galindo C, Wilson MW. J Clin Oncol. 2017 Jan;35(1):72-77.

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.


Full title:

Study of Treatment for Patients with Cancer of the Eye—Retinoblastoma (RET5)

Study goal:

To estimate the ocular survival and event-free survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.



Clinical trials categories:

Solid Tumors Childhood Cancer Retinoblastoma

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