Retinoblastoma medical therapy

The optimal therapy for retinoblastoma depends on the stage at diagnosis. Systemic chemotherapy via carboplatin, etoposide, and vincristine (CEV) is the most common regimen used to treat retinoblastoma.

• The priority of retinoblastoma treatment is to:^[1]
  • Save the life of the child
  • Preserve vision
  • Minimize complications or side effects of treatment
• The exact course of treatment will depend upon the individual case and will be decided by the ophthalmologist in discussion with the pediatric oncologist.
• Children with the involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy and local therapies).
  
• The choice of therapy depends upon several factors, such as:^[2]
  • Tumor size
  • Tumor location
  • Presence or absence of vitreous or subretinal seeds
  • Age of the patient

• Systemic chemotherapy has become the forefront of treatment in the past decade, in search of globe preserving measures and to avoid the adverse effects of radiation therapy.^[3]
  
• The common indications for systemic chemotherapy include:
  • Unilateral intraocular retinoblastoma with high risk features
  • Bilateral intraocular retinoblastoma
  • Prophylaxis against metastasis following enucleation in the presence of histopathologic high-risk features
  • Extraocular retinoblastoma with local and/or regional spread
  • Metastatic retinoblastoma with or without CNS involvement
  • Trilateral retinoblastoma

Chemotherapy Regimen

• The most common chemotherapy regimen for retinoblastoma is the combination of the following:^[4][5][6]
  • Carboplatin
  • Etoposide
  • Vincristine
• This combination may be used with different dose of medication and frequency depending upon the stage of the tumor.
  • Usually, the treatment regimen is comprised of either three sessions of high dose regimen or six sessions of low dose regimen.
  • Low dose regimen:
    • Carboplatin 18.6 mg/kg IV q24h for one day and repeated every (21 – 28) days
    • Etoposide 5 mg/kg IV q24h for two days and repeated (21 – 28) days
    • Vincristine 0.05 mg/kg IV q24h for one day and repeated every (21 – 28) days
  • High dose regimen:
    • Carboplatin 28 mg/kg IV q24h for one day and repeated every (21 – 28) days
    • Etoposide 12 mg/kg IV q24h for two days and repeated every (21 – 28) days
    • Vincristine 0.05 mg/kg IV q24h for one day and repeated every (21 – 28) days
  • The above mentioned dosage is recommended for orbital retinoblastoma and is subject to change for other types of tumor presentation.

• Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, aorta, and the neck directly into the optic vessels.

• Other treatment modalities which are currently available for retinoblastoma include:^[7]

• The feasibility of external beam radiotherapy depends on the stage of retinoblastoma at the time of diagnosis.
  
• The globe preservation rate with this method varies according to the stage of the tumor at the time of diagnosis:

• Groups I–II eyes: 95%

• Groups IV and V eyes: 50%

• This method is indicated as salvage therapy for seeding following unsuccessful chemotherapy, however, the decision to use this method of treatment must be made on a case by case basis.
  
• The dose to target tumor cells of retina ranges from 3,600 to 4,500 cGy administered in 180 – 200 cGy daily fractions 5 times/week.
  
• Contraindications of EBRT:
  • Children less than 1 year of age (due to the risk of secondary malignancies)
  • Eyes with dismal visual potential

• Indications:
  • Primary treatment
  • Residual tumor following photocoagulation/thermotherapy/thermo–chemotherapy/cryotherapy
  • Tumor recurrence
  • Tumor size less than 15 mm in diameter
• Contraindication:
  • Presence of diffuse vitreous seeding

• Indications:
  • Tumors not larger than 3 mm in diameter with no evidence of seeding, and located posterior to the equator
  • Primary treatment
  • Consolidation treatment
  • Tumor recurrence

• Indications:
  • Tumors not larger than 12 mm in diameter with no evidence of seeding, and located posterior to the equator
  • Consolidation treatment

• This method is indicated for intraocular retinoblastoma and one of the following factors:
  • Consolidation of large tumors after systemic chemotherapy
  • For the treatment of small peripheral or posterior tumors as the sole modality
  • For the eradication of small tumor recurrences following chemotherapy and/or radiotherapy
• This method is suitable for treating tumors with the following characteristics:
  • 3.0 mm or less in diameter
  • 2.0 mm or less in thickness
  • Without seeding into the adjacent vitreous

• Indications:
  • Tumors not larger than 3 mm in diameter, with no evidence of seeding, and located anterior to the equator
  • Primary treatment
  • Consolidation treatment
  • Tumor recurrence