eMedicine Specialties > Ophthalmology > Retina

Retinoblastoma: Treatment & Medication

Author: Marichelle Aventura Isidro, MD, Consulting Staff, Department of Ophthalmology, Santo Tomas University Hospital of Manila, Philippine Heart Center
Coauthor(s): Manolette R Roque, MD, MBA, DPBO, FPAO, President and CEO, Chief of Service, Ocular Immunology and Uveitis, Consulting Staff, Cornea and Refractive Surgery, Eye Republic Ophthalmology Clinic; General Manager, Ophthalmic Consultants Philippines Co; Consulting Staff, CME Liaison, Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center; Thomas M Aaberg, Jr, MD, Clinical Assistant Professor, Department of Surgery, Michigan State University College of Human Medicine; Consulting Staff, Department of Ophthalmology, Associated Retinal Consultants; Barbara L Roque, MD, Full Partner, Ophthalmic Consultants Philippines Co, Chief of Service, Pediatric Ophthalmology and Strabismus, Consulting Staff, Orbit and Eye Plastics, Eye Republic Ophthalmology Clinic
Contributor Information and Disclosures

Updated: Jan 21, 2009

Treatment

Medical Care

Medical therapy should be directed toward complete control of the tumor and the preservation of as much useful vision as possible. Treatment is usually individualized to the specific patient.

  • External beam radiation therapy
    • Incidence of local control is high and retinal late effects are minimal with radiation doses of 4000-4500 cGy used with 200 cGy fractions. However, morbidity and mortality associated with external beam radiation therapy (EBRT) are significant. EBRT results in cessation of bone growth. Therefore, children with retinoblastoma who are treated with EBRT have significant midface hypoplasia. (The younger the child is when EBRT is instituted, the more dramatic the outcome.) More importantly, EBRT has been shown to increase the risk of developing second cancers almost 6-fold during the lifetime of these patients. Today, neoadjuvant chemotherapy (chemoreduction) has superseded EBRT in order to (hopefully) circumvent these terrible adverse effects of EBRT. Nevertheless, EBRT is still indicated in selected circumstances, as follows:
      • For eyes with significant vitreous seeding
      • For children who have progression of disease while undergoing chemoreduction
      • For tumors extending up to or beyond the cut margin of the optic nerve of an enucleated eye (The best method of treatment is being debated in such a case.)
  • Radioactive isotope plaques
    • Use of radioactive 60 Co (cobalt); radioactive 125 I (iodine), which is presently the most used; radioactive 192 Ir (iridium); or radioactive 106 Ru (ruthenium)
    • Radioactive 125 I plaque treatment is recommended for treatment of one larger tumor or a limited number of moderately sized tumors (<3) present in noncritical areas.
    • Advantage - Locally directed treatment to the tumor, minimizing radiation to the normal tissue
    • Disadvantage - Incomplete treatment, high dose to local sclera, significantly less irradiation for anterior lesions, and difficulty placing posterior plaques
  • Chemotherapy
    • Primary neoadjuvant chemotherapy or chemoreduction has been the most significant recent advance in the treatment of retinoblastoma. This is typically the principle mode of treatment for eyes in intraocular groups C and D. However, our understanding of dose, duration, and end points are still evolving with this relatively new treatment modality.
    • Prophylactic chemotherapy is recommended if a tumor is in the optic nerve past the lamina cribrosa because these cases have a poor survival prognosis.
    • Use of neoadjuvant chemotherapy has the advantage of limiting the necessity for EBRT and reducing the possibility of EBRT-related complications.
    • Chemotherapy also may be used prior to EBRT, as completed by Kingston and associates in an attempt to improve local control and visual outcome in children with group V tumors, using carboplatin, etoposide, and vincristine, followed by 40-44 Gy of EBRT.13
    • Shields and associates used carboplatin, etoposide, and vincristine chemotherapy, followed by cryotherapy, photocoagulation, and 125 I plaque treatment in an attempt to improve outcome for eyes with more advanced retinoblastoma commonly treated with enucleation.14
    • Current studies completed by the Retinoblastoma Study Group show the promising use of chemotherapy (carboplatin, vincristine sulfate, and etoposide phosphate) as a primary mode of treatment in reducing tumor bulk, followed by various forms of local approaches (radiotherapy [external beam or plaque], cryotherapy, thermotherapy, and photocoagulation) that can be used for final tumor control.
    • Some reports suggest the addition of cyclosporine in combination with the chemotherapy regimen of carboplatin, etoposide, and vincristine. These reports showed that this addition enhances the efficacy of chemotherapy and eliminates the need for radiation.

Surgical Care

Surgical removal of the tumor has been the standard management of very unfavorable retinoblastoma cases.

  • Enucleation
    • Enucleation is performed when there is no chance of preserving useful vision in an eye.
    • Patients generally requiring enucleation are those who present with total retinal detachments and/or the posterior segment is full of the tumor, in which case it is clear the patient cannot retain any form of useful vision.
  • Cryotherapy
    • Cryotherapy can be used primarily for small anteriorly located tumors, remote from the disc and macula but also may be indicated for recurrence after radiation therapy.
    • Cryotherapy is performed transsclerally. Under direct visualization, freezing is carried out until the ice ball incorporates the entire tumor. A refreeze-thaw cycle is repeated 3-4 times.
    • Complete disappearance of the tumor with a flat pigmented scar is the sign of successful treatment. This can be repeated if the tumor does not respond initially.
  • Photocoagulation
    • Photocoagulation can be used as primary therapy for small posteriorly located tumors.
    • There is a danger of producing large field defects near the disc and decreased vision resulting from macular pucker by photocoagulation near the macula.
    • The technique is performed by placing a double row of confluent burns around each tumor using a photocoagulator.
    • It is important not to do direct treatment on the tumor itself because the light color of the tumor generally precludes absorption of sufficient energy and there is a danger of exploding the tumor with spread of viable tumor debris into the vitreous and other parts of the retina.
    • Successful treatment with photocoagulation takes weeks to evolve and consists of complete disappearance of the tumor, which is replaced with a flat area.
    • Photocoagulation can also be used for tumor recurrences after EBRT.
  • Exenteration is still performed, especially in most underdeveloped countries, when extension of the tumor into the surrounding areas is considerable.

Consultations

Patients with retinoblastoma should be evaluated and treated by a team of medical professionals, including an ophthalmologist (preferably an ocular oncologist), pediatrician, oncologist, radiologist, and pathologist. Given that this is a relatively uncommon disease, patients should try to seek attention from physicians with subspecialty training and experience in retinoblastoma, and who are actively participating in organizations that explore up-to-date treatments for retinoblastoma.

  • The pathologist plays a special role in the treatment of a patient with retinoblastoma. The surgical specimens should be evaluated with care to guide the clinicians with the appropriate postsurgical management.
  • Appropriate consultations are needed to provide much needed information to each other. In some instances, frozen sections are requested after enucleation or exenteration.

Medication

Use of chemotherapeutic drugs should be limited to specific group of patients for whom the benefits outweigh the potential disadvantages.

Anticancer drugs

Used for management of metastasis but also used as adjuvant therapy for patients with high-risk retinoblastoma.


Vincristine (Vincasar, Oncovin PFS)

Cycle-specific and phase-specific, which blocks mitosis in metaphase. Binds to microtubular protein, tubulin, GTP dependent. Blocks ability of tubulin to polymerize to form microtubules, which leads to rapid cytotoxic effects and cell destruction.

Adult

2 mg IV push

Pediatric

1.5 mg/m2 (0.05 mg/kg for children < 36 mo; not to exceed 2 mg/dose) IV q2wk for 9 cycles

Neurotoxicity may be additive with drugs acting on the peripheral nervous system; allopurinol may increase incidence of cytotoxic-induced bone marrow depression

Documented hypersensitivity to vinca alkaloids

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with impaired hepatic function or biliary obstruction


Carboplatin (Paraplatin)

Inhibits both DNA and RNA synthesis. Binds to protein and other compounds containing SH group. Cytotoxicity can occur at any stage of the cell cycle, but cell is most vulnerable to action of these drugs in G1 and S phase.

Adult

360 mg/m2 IV q3wk as monotherapy or 300 mg/m2 q4wk as combination therapy

Pediatric

For retinoblastoma: 560 mg/m2 (18.6 mg/kg for children < 36 mo) IV q3wk for 9 cycles

Nephrotoxicity increases with aminoglycosides and other nephrotoxic drugs

Documented hypersensitivity; preexisting severe renal impairment and myelosuppression; severe allergy to platinum components

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in pregnancy and breastfeeding; peripheral blood counts and neurologic and renal functions to be monitored closely


Etoposide (Toposar, VePesid)

Blocks cells in the late S-G2 phase of the cell cycle. Binding of drugs to enzyme-DNA complex results in persistence of transient cleavable form of complex and, thus, renders it susceptible to irreversible double strand breaks.

Adult

100 mg/m2 IV days 1-5

Pediatric

For retinoblastoma: 150 mg/m2 (5 mg/kg for children <36 mo) IV q3wk for 9 cycles

May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells

Documented hypersensitivity; myelosuppression; liver impairment; IT administration may cause death

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Bleeding and severe myelosuppression may occur

Immunosuppressants

The addition of cyclosporine in combination with chemotherapy regimen of carboplatin, etoposide, and vincristine reportedly have showed enhanced efficacy of chemotherapy.


Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease for a variety of organs. For children and adults, base dosing on ideal body weight.

Adult

Initial PO dose: 14-18 mg/kg/d PO 4-12 h
Maintenance PO dose: 5-15 mg/kg/d PO qd or divided bid
Initial IV dose: 5-6 mg/kg IV qd 4-12 h
Maintenance IV dose: 2-10 mg/kg/d IV divided q8-12h

Pediatric

Administer as in adults q3wk for 9 cycles

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO

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References
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Further Reading

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Keywords

intraocular cancer, intraocular childhood malignancy, eye tumor, ocular tumor, ocular malignancy, RB gene, retinoblastoma gene, childhood cancer, eye cancer

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Contributor Information and Disclosures

Author

Marichelle Aventura Isidro, MD, Consulting Staff, Department of Ophthalmology, Santo Tomas University Hospital of Manila, Philippine Heart Center
Marichelle Aventura Isidro, MD is a member of the following medical societies: American Academy of Ophthalmology and International Society of Refractive Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Manolette R Roque, MD, MBA, DPBO, FPAO, President and CEO, Chief of Service, Ocular Immunology and Uveitis, Consulting Staff, Cornea and Refractive Surgery, Eye Republic Ophthalmology Clinic; General Manager, Ophthalmic Consultants Philippines Co; Consulting Staff, CME Liaison, Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center
Manolette R Roque, MD, MBA, DPBO, FPAO is a member of the following medical societies: American Academy of Ophthalmic Executives, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, American Society of Ophthalmic Administrators, American Uveitis Society, International Ocular Inflammation Society, Philippine Medical Association, Philippine Ocular Inflammation Society, and Philippine Society of Cataract and Refractive Surgery
Disclosure: Nothing to disclose.

Thomas M Aaberg, Jr, MD, Clinical Assistant Professor, Department of Surgery, Michigan State University College of Human Medicine; Consulting Staff, Department of Ophthalmology, Associated Retinal Consultants
Thomas M Aaberg, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Medical Association, American Society of Retina Specialists, Michigan Society of Eye Physicians & Surgeons, and Retina Society
Disclosure: Novartis Consulting fee Consulting

Barbara L Roque, MD, Full Partner, Ophthalmic Consultants Philippines Co, Chief of Service, Pediatric Ophthalmology and Strabismus, Consulting Staff, Orbit and Eye Plastics, Eye Republic Ophthalmology Clinic
Disclosure: Nothing to disclose.

Medical Editor

Gerhard W Cibis, MD, Clinical Professor, Director of Pediatric Ophthalmology Service, Department of Ophthalmology, University of Kansas, Kansas City
Gerhard W Cibis, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, and American Ophthalmological Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine
Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society
Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Consulting

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
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