Chemotherapy for Eye Cancer

doi:10.1016/S0039-6257(00)00210-1

Survey of Ophthalmology

Volume 45, Issue 5, March–April 2001, Pages 416-444

https://doi.org/10.1016/S0039-6257(00)00210-1 Get rights and content

Abstract

Chemotherapy has been used to treat a multitude of eye cancers. We attempted to review the role of chemotherapy in the treatment of ocular, adnexal, and orbital malignancies by conducting an extensive search of the medical literature. Unfortunately, the published reports typically contain few patients with limited follow-up, precluding definitive recommendations. For most eye cancers, multicenter trials will offer the potential to gather the numbers of patients required to determine the clinical utility of chemotherapy.

Section snippets

Basal cell, squamous cell, and sebaceous cell carcinoma of the eyelid

Basal cell carcinoma (BCC) is the most common malignant tumor of the eyelids and periorbital tissues, followed by squamous cell carcinoma (SCC), sebaceous cell carcinoma, and malignant melanoma.126, 127, 128, 179, 180, 186, 201, 208, 216 Methods of treatment include surgical excision, chemosurgery, cryotherapy, and irradiation.126, 127, 128, 179, 180, 201, 208, 216 Large and deeply invasive eyelid carcinomas are often unresectable and pose difficult management problems. Chemotherapy has been

Retinoblastoma

Retinoblastoma is the most common primary intraocular tumor in children. Enucleation remains the definitive curative treatment, but children's eyes and vision have been salvaged with the use of radiation, laser photocoagulation, cryotherapy, and chemotherapy.2, 113, 202, 203, 267, 270, 271, 294 Treatments have been applied both singularly and in combination. Tumor size, number, location and the presence of unilateral or bilateral disease are all factors influencing treatment. The presence of

Rhabdomyosarcoma

Rhabdomyosarcoma is the most common primary malignant neoplasm of the orbit in children. Rhabdomyosarcoma can arise in multiple parts of the body, including the head and neck, the extremities, the genitourinary tract, and the trunk. Rhabdomyosarcoma has a distinct predilection for younger patients, with an average age at presentation of 7 years. Rhabdomyosarcomas represent 5% of all childhood cancers and are the most common soft-tissue sarcomas in the pediatric age group. Between 15–25% of all

Metastasis of solid tumors to the uvea

The most common intraocular tumors are uveal metastases (Table 5).84, 155 Bloch and Gartner found a 12% incidence of ocular metastases in patients who died of cancer.²⁹ The metastases often were clinically undetected. Tumors most commonly metastasize from the breast in women and from the lung in men.81, 82, 196 Ocular metastases most commonly involve the uveal tract, in particular the choroid.²²⁹ Choroidal metastases are often bilateral and multifocal, typically becoming symptomatic when the

Side Effects of Chemotherapy

The toxicity associated with chemotherapy must be considered. Chemotherapy should be used judiciously due to potentially serious side effects.103, 119 Systemic chemotherapy should be administered under the direction of a medical or pediatric oncologist. Table 6 summarizes the chemotherapeutic agents discussed in this paper and highlights the systemic toxicity of each. For a more complete discussion, the authors recommend that the reader consult Goodman and Gilman's: The Pharmacological Basis of

Summary and Conclusions

In this review we have summarized advances in the use of chemotherapy for the treatment of ocular and adnexal malignancies. We have been subject to the limitations of our specialty and the relatively limited number of reported ocular and adnexal tumors. So, what may at first appear as a review of case reports, small series, and incidental findings is actually a consolidation of the medical literature with an analysis of the emerging trends. Although this does not substitute for a well

Methods of Literature Search

We conducted a MEDLINE search covering the years 1966 through 2000 (as available) using the search words chemotherapy, retinoblastoma, rhabdomyosarcoma, melanoma, leukemia, lymphoma, basal, squamous, sebaceous, pseudotumor, metastasis, eye, lid, conjunctiva, iris, retina, choroid, ciliary body, and orbit. Additional references, particularly those before 1966, were obtained from the bibliographies of articles obtained from the MEDLINE search.

Certain references were added as a result of the

Outline

I. Chemotherapy for eyelid, conjunctival and periorbital tumors

A. Basal cell, squamous cell, and sebaceous cell carcinoma of the eyelid

B. Malignant melanoma and squamous cell carcinoma of the conjunctiva

C. Summary

II. Chemotherapy for primary intraocular tumors

A. Retinoblastoma

1. Treatment of intraocular retinoblastoma: evolution of chemoreduction

2. Adjuvant chemotherapy for retinoblastoma

3. Chemotherapy for ocular salvage

4. Extraocular retinoblastoma

a. Gross orbital extension

b. Central nervous

Acknowledgements

The authors have no proprietary interest in any product or concept described in this article. This work was supported in part by The EyeCare Foundation, Inc., New York, NY; Research to Prevent Blindness, Inc., New York, NY; and the St. Giles Foundation, New York City, NY. Dr Czechonska received a fellowship grant from The Kosciuszko Foundation.

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Radiation therapy is widely used for the treatment of orbital tumors and inflammatory disease. Both external beam teletherapy and implant brachytherapy radiation techniques are employed. External beam radiation therapy is the most common. It involves directing an external radiation source towards the eye, sinuses, and orbit. Whereas most patients are treated with linear accelerator–derived external beam radiation therapy, proton, neutron stereotactic radiosurgery, gamma knife, and intensity-modulated radiation therapy have become more available in developed countries. Radiation can be used alone or together with surgery or chemotherapy. Implant radiation therapy (brachytherapy) is also used to treat orbital tumors. Brachytherapy involves surgical placement of radiation sources within the tumor or targeted volume. Characteristically conformal, brachytherapy increases the dose within the target while maximally decreasing exposure of normal tissues. Orbital brachytherapy can be used to boost the dose to the target volume prior to orbital external beam radiation therapy. Herein, I explore the unique challenges associated with irradiation of the orbit, basic radiobiology, doses, indications, and results of treatment. The tolerances of normal ocular and orbital tissues are reported. This review of the literature offers a unique perspective, synthesizing the world's experience on the use of orbital radiation therapy.
Topical Interferon Alfa in the Treatment of Conjunctival Melanoma and Primary Acquired Melanosis Complex
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To report on topical interferon alfa-2b for conjunctival malignant melanoma (CMM) and primary acquired melanosis with atypia (PAM).
Retrospective, interventional case series.
Five eyes of five consecutive patients with biopsy-proven malignant melanoma were treated with topical interferon alfa-2b as treatment for primary or recurrent disease. One drop of interferon alfa-2b (1 million units/ml) was placed into the superior fornix four times daily for three months. Punctal plugs limited systemic absorption. The main outcome measure was tumor regression by clinical examination and comparative slit-lamp photography.
Five consecutive patients with conjunctival melanoma (American Joint Committee on Cancer-International Union Against Cancer stages T2 [n = 3] and T3 [n = 2]) were included. Two patients had recurrent corneal tumors, eight and 13 months after local excision, cryotherapy, and topical mitomycin C therapy. Two months after topical interferon alfa-2b treatment, the lesions regressed without side effects. Two additional patients (who could not tolerate topical mitomycin C) were switched to topical interferon alfa-2b. They experienced transient chemical conjunctivitis and have no signs of recurrence (mean, 15 months of follow-up). The fifth had recurrent tumor despite multiple surgeries. This melanoma did not respond to topical interferon alfa-2b nor did the patient tolerate treatment (keratoconjunctivitis). No systemic side effects were noted.
We present evidence that conjunctival and corneal melanoma regresses after exposure to topical interferon alfa-2b. A larger-scale longer-term study must evaluate the long-term efficacy and safety of this therapy.
Whole body positron emission tomography/computed tomography staging of metastatic choroidal melanoma
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To evaluate whole-body positron emission tomography (PET)/computed tomography in staging of patients with metastatic choroidal melanoma.
Interventional non-randomized clinical study.
Twenty patients were referred for whole-body 18-fluoro-2-deoxy-D-glucose (FDG) PET/computed tomography imaging because of suspected metastatic choroidal melanoma. PET/computed tomography images were studied for the presence and distribution of metastatic melanoma. Subsequent biopsies were performed to confirm the presence of metastatic disease.
Twenty patients underwent PET/computed tomography. Eighteen were imaged because of abnormal clinical, hematologic, or radiographic screening studies during the course of their follow-up after plaque brachytherapy or enucleation. Two were imaged before treatment of their primary tumor. PET/computed tomography revealed or confirmed metastatic melanoma in eight (40%) of these 20 patients. The mean time from initial diagnosis to metastasis was 47 months (range 0 to 154). The most common sites for metastases were the liver (100%), bone (50%), lung (25%), lymph nodes (25%), and subcutaneous tissue (25%). Cardiac, brain, thyroid, and posterior abdominal wall lesions (12.5%) were also noted. Six patients (75%) had multiple organ involvement. No false positives were noted. PET/computed tomography imaging also detected benign lesions of the bone and lymph nodes in three patients (15%). All patients had hepatic metastases and liver enzyme assays were abnormal in only one (12.5%) of eight patients.
PET/computed tomography imaging is a sensitive tool for the detection and localization of hepatic and extra-hepatic (particularly osseous) metastatic choroidal melanoma.
Choroidal metastasis: Case reports and review of the literature
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Choroidal metastases are recognized as the most common intraocular malignancy. Their diagnosis has become more common due to increased emphasis on comprehensive eye examinations for cancer patients and the improved life expectancy of patients with metastatic disease. They are most prevalent in female patients with breast cancer and male patients with lung cancer.
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Two case reports of patients diagnosed with choroidal metastases are discussed. Case 1 involved a patient with lung cancer who manifested a large bullous exudative retinal detachment due to an underlying choroidal metastasis. Case 2 dealt with treatment of a patient with metastatic transitional cell cancer who manifested a shallow exudative retinal detachment caused by a choroidal metastasis.
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Visual recovery after radiation therapy for bilateral subfoveal acute myelogenous leukemia (AML)
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Present a case of bilateral foveal acute myelogenous leukemic tumors that responded to radiation therapy.
Case report.
A patient was diagnosed with bilateral subfoveal infiltration of known systemic acute myelogenous leukemia. He received a standard induction chemotherapy, followed by consolidation therapy for his systemic leukemia. However, despite a complete marrow response, the intraocular tumors did not regress. Therefore, he was given low dose (1950-cGy) ocular external beam radiation therapy.
One course of systemic cytarabine chemotherapy failed to control the subfoveal tumors, leaving the patient at risk for permanent vision loss. In contrast, external beam radiation therapy improved his vision from 20/60 in his right eye to 20/20 and from 20/70 in his left eye to 20/25.
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Reviews in medicineChemotherapy for Eye Cancer

Abstract

Section snippets

Basal cell, squamous cell, and sebaceous cell carcinoma of the eyelid

Retinoblastoma

Rhabdomyosarcoma

Metastasis of solid tumors to the uvea

Side Effects of Chemotherapy

Summary and Conclusions

Methods of Literature Search

Outline

Acknowledgements

Ophthalmology

Ophthalmology

Hematol Oncol Clin North Am

Surv Ophthalmol

A comparative study of mitomycin C and

Ophthalmology

Ophthalmology

Surv Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Cancer Treat Rev

Ophthalmology

Ophthalmology

J Pediatr Surg

Am J Ophthalmol

Surv Ophthalmol

Ophthalmology

Ophthalmology

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chemotherapy in intraocular metastasis from carcinoma of the breast

Acta Ophthalmol (Suppl)

Retinoblastomadiagnosis and management

CA Cancer J Clin

Simultaneous bilateral radiation for advanced bilateral retinoblastoma

Arch Ophthalmol

Treatment of bilateral groups I through III retinoblastoma with bilateral radiation

Arch Ophthalmol

The management of unilateral retinoblastoma without primary enucleation

Arch Ophthalmol

Medical therapy of retinoblastoma in children

J Neurosurg Sci

Cobalt plaque versus enucleation for uveal melanomacomparison of survival rates

Br J Ophthalmol

Chemotherapy for retinoblastoma

Ophthalmic Paediatr Genet

Ocular involvement in leukemia and allied disorders

Arch Ophthalmol

Successful treatment of orbital rhabdomyosarcoma in two infants using chemotherapy alone

Med Pediatr Oncol

Radiotherapy of retinoblastoma. A review of 63 children treated with different irradiation techniques

Cancer

Retinoblastoma experience in a developing country

Med Pediatr Oncol

Enucleation vs cobalt plaque radiotherapy for malignant melanomas of the choroid and ciliary body

Arch Ophthalmol

Intraocular reticulum-cell sarcomaclinico-pathologic study of four cases and review of the literature

Surv Ophthalmol

Treatment of intraocular lymphoma with high-dose Ara-C

Cancer

Prognosis in metastatic choroidal melanoma

South Med J

Leukemic iris infiltration as the only site of relapse in a child with acute lymphoblastic leukemiatemporary remission with high-dose chemotherapy

Med Pediatr Oncol

Primary conjunctival lymphomaresponse to chemotherapy in 4 cases

Acta Haematol

Alteration of methotrexate uptake in human leukemia cells by other agents

Cancer Res

Sequential cisplatin/VM-26 and vincristine/cyclophosphamide/doxorubicin in metastatic neuroblastomaan effective alternating non-cross- resistant regimen?

J Clin Oncol

The incidence of ocular metastatic carcinoma

Arch Ophthalmol

Methotrexate as relapse therapy for rhabdomyosarcoma

Am J Pediatr Hematol Oncol

Radioimmunoscintigraphy of ocular melanoma with 99mTc labelled cutaneous melanoma antibody fragments

Br J Ophthalmol

Response of a choroidal metastasis to multiple-drug chemotherapy

Cancer

Reviews in medicine
Chemotherapy for Eye Cancer