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Chemotherapy Plus Local Treatment in the Management of Intraocular Retinoblastoma

Chemotherapy Plus Local Treatment in the Management of Intraocular Retinoblastoma Abstract Objective: To describe platinum-based chemotherapy combined with local treatment modalities as an alternative to external beam radiotherapy for intraocular retinoblastoma. Design: Platinum levels were measured by atomic absorption analysis in the tumors of 2 patients with retinoblastoma given carboplatin 5 or 2.5 hours before enucleation. Platinum levels in heated vs nonheated Greene melanoma tumors in rabbits were compared. A retrospective review of 172 affected eyes in 136 consecutive patients treated for retinoblastoma between January 1990 and December 1995 was performed. From 1990 to 1992, all treatable eyes initially received systemic carboplatin, 560 mg/m2, followed by 15 to 30 minutes of continuous diode laser hyperthermia (thermochemotherapy). Since 1992, larger tumors were treated initially with 3 monthly cycles of carboplatin, etoposide, and vincristine sulfate to reduce tumor volume (chemoreduction) followed by sequential aggressive local therapy (SALT) during examinations under anesthesia every 2 to 3 weeks. Outcome Measure: Treatment success was defined as eradication of tumor without enucleation or external beam radiotherapy. Results: Significant therapeutic platinum levels were measured in the human tumors 2.5 and 5 hours after carboplatin administration. Increasing the temperature by 9°C for 15 minutes doubled platinum levels in the rabbit model. Of the 38 eyes with Reese-Ellsworth group 1 through 5b tumors that were treated primarily with thermochemotherapy, all 24 eyes with group 1 and 2 tumors were treated successfully and two of the 4 eyes with group 3 tumors and all 10 eyes with group 5b tumors were treated unsuccessfully. Chemoreduction plus SALT was the primary treatment in 35 eyes and was successful in all 10 eyes with group 1 through 4 tumors and unsuccessful in all 7 eyes with extensive subretinal seeding and all 18 eyes with group 5b tumors with vitreous seeding. Seventy patients received carboplatin or carboplatin, vincristine, and etoposide, with myelosuppression, occasionally associated with bacteremia, being the main side effect. Transfusions were required in 15% of patients. Radiation retinopathy occurred in all 6 eyes treated with iodine 125 plaques. Conclusions: Thermochemotherapy is successful primary treatment for Reese-Ellsworth group 1 and 2 retinoblastomas. For larger tumors in the absence of vitreous or extensive subretinal seeding, 3 cycles of chemoreduction followed by SALT eradicates residual viable tumor. Chemoreduction plus SALT was not successful in eyes with diffuse vitreous or extensive subretinal seeding. Prior chemotherapy increases the risk for radiation retinopathy following 125I plaque therapy. External beam radiotherapy can safely be avoided in the primary treatment of Reese-Ellsworth groups 1 through 4 nondispersed retinoblastoma. References 1. Eng C, Lin FP, Abramson DH, et al. Mortality from second tumors among long-term survivors of retinoblastoma . J Natl Cancer Inst . 1993;85:1121-1128.Crossref 2. MacFaul PA, Bedford MA. Ocular complications after therapeutic irradiation . Br J Opthalmol . 1970;54:237-247.Crossref 3. Imhof SM, Mourits MP, Hofman P, et al. Quantification of orbital and mid-facial growth retardation after megavoltage external beam irradiation in children with retinoblastoma . Ophthalmology . 1996;103:263-268.Crossref 4. Messmer EP, Sauerwein W, Heinrich T, et al. New and recurrent tumor foci following local treatment as well as external beam radiotherapy radiation in eyes of patients with hereditary retinoblastoma . Graefes Arch Clin Exp Ophthalmol . 1990;228:426-431.Crossref 5. White L. The role of chemotherapy in the treatment of retinoblastoma . Retina . 1983;3:194-199.Crossref 6. Haye C, Desjardins L, Elmaleh C, et al. Prognosis and treatment of retinoblastoma: 105 cases treated at Institut Curie . Ophthalmic Paediatr Genet . 1989;10:151-155.Crossref 7. Bin P, Boddy AV, English MW, et al. The comparative pharmacokinetics and pharmacodynamics of cisplatin and carboplatin in paediatric patients: a review . Anticancer Res . 1994;14;2279-2283. 8. Gaynon PS. Carboplatin in pediatric malignancies . Semin Oncol . 1994;21( (5 suppl 12) ):65-76. 9. Cairo MS. The use of ifosfamide, carboplatin, and etoposide in children with solid tumors . Semin Oncol . 1995;22( (3 suppl 7) ):23-27. 10. Lewis IJ, Strauss MC, Pearson A, Pinkerton CR, Stevens R. Phase II study of carboplatin in childhood tumors . Proc Am Soc Clin Oncol . 1993;12:A1413. Abstract. 11. Riccardi R, Riccardi A, DiRocco C, et al. Cerebrospinal fluid pharmacokinetics of carboplatin in children with brain tumors . Cancer Chemother Pharmacol . 1992;30:21.Crossref 12. Doz F, Neuenschwander S, Plantaz D, et al. Etoposide and carboplatin in extraocular retinoblastoma: a study by the Societe Francaise d'Oncologie Pediatrique . J Clin Oncol . 1995;13:902-909. 13. Hahn GM. Thermal enhancement of the actions of anticancer agents . In: GM Hahn, ed. Hyperthermia and Cancer . New York, NY: Plenum Publishing Corp; 1982:55-86. 14. Da Silva VF, Raaphorst GP, Goyal R, Feeley M. Drug cytotoxicity at elevated temperature: in vitro study on the U-87MG glioma cell line . J Neurosurg . 1987;67:885-888.Crossref 15. Herman TS, Teicher BA. Summary of studies adding systemic chemotherapy to local hyperthermia and radiation . Int J Hyperthermia . 1994;10:443-449.Crossref 16. Tapazoglu E, Cohen JD, Schmitt CL, Khatara A, Sapareto SA, Robins HI. Whole body hyperthermia and carboplatin: cytotoxicity for murine leukemia and normal marrow . Br J Cancer . 1991;64:528-530.Crossref 17. Murphree AL, Cote M, Gomer CJ. The evolution of photodynamic therapy techniques in the treatment of intraocular tumors . Photochem Photobiol . 1987;46:919-923.Crossref 18. Reed E, Sauerhoff S, Poirier MC. Quantitation of platinum-DNA binding in human tissues following therapeutic levels of drug exposure: a novel use of graphite furnace spectrometry . Atomic Spectroscopy . 1988;9:93-95. 19. Reed E, Ozols RF, Tarone R, Yuspa SH, Poirier MC. Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy . Proc Natl Acad Sci U S A . 1987;84:5024-5028.Crossref 20. McCormick B, Ellsworth R, Abramson D, Losasso T, Grabowski E. Results of external beam radiotherapy for children with retinoblastoma: a comparison of two techniques . J Pediatr Ophthalmol Strabismus . 1989;26:239-243. 21. Kinyoun JL, Zamber RW, Lawrence BS, Barlow WE, Arnold AM. Photocoagulation treatment for clinically significant radiation macular oedema . Br J Ophthalmol . 1995;79:144-149.Crossref 22. Elsas T, Thorud E, Jetne V, Conradi IS. Retinopathy after low dose irradiation for an intracranial tumor of the frontal lobe: a case report . Acta Ophthalmol . 1988;66:65-68.Crossref 23. Amoaku WM, Archer DB. Cephalic radiation and retinal vasculopathy . Eye . 1990;4:195-203.Crossref 24. Archer DB, Amoaku WM, Gardiner TA. Radiation retinopathy: clinical, histopathological, ultrastructural and experimental correlations . Eye . 1991;5:239-251.Crossref 25. O'Brien ME, Tonge K, Blake P, Moskovic E, Wiltshaw E. Blindness associated with high-dose carboplatin . Lancet . 1992;339:558.Crossref 26. Rankin EM, Pitts JF. Ophthalmic toxicity during carboplatin therapy . Ann Oncol . 1993;4:337-338. 27. Winick NJ, McKenna RW, Shuster JJ, et al. Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide . J Clin Oncol . 1993;11:209-217. 28. Tucker MA, Meadows AT, Boice JD Jr, et al. Cancer risk following treatment of childhood cancer . In: Boice JD Jr, Fraumeni JF Jr, eds. Radiation Carcinogenesis, Epidemiology and Biological Significance . New York, NY: Raven Press; 1984:211-224. 29. Wolter JR. Growth retardation of the orbital region after radiation treatment of retinoblastoma: causing a very typical physiognomy . J Pediatr Ophthalmol Strabismus . 1974;11:125-128. 30. Gallie BL, Budning A, DeBoer G, et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy . Arch Ophthalmol . 1996;114:1321-1328.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Chemotherapy Plus Local Treatment in the Management of Intraocular Retinoblastoma

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References (33)

Publisher
American Medical Association
Copyright
Copyright © 1996 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1996.01100140548005
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Abstract

Abstract Objective: To describe platinum-based chemotherapy combined with local treatment modalities as an alternative to external beam radiotherapy for intraocular retinoblastoma. Design: Platinum levels were measured by atomic absorption analysis in the tumors of 2 patients with retinoblastoma given carboplatin 5 or 2.5 hours before enucleation. Platinum levels in heated vs nonheated Greene melanoma tumors in rabbits were compared. A retrospective review of 172 affected eyes in 136 consecutive patients treated for retinoblastoma between January 1990 and December 1995 was performed. From 1990 to 1992, all treatable eyes initially received systemic carboplatin, 560 mg/m2, followed by 15 to 30 minutes of continuous diode laser hyperthermia (thermochemotherapy). Since 1992, larger tumors were treated initially with 3 monthly cycles of carboplatin, etoposide, and vincristine sulfate to reduce tumor volume (chemoreduction) followed by sequential aggressive local therapy (SALT) during examinations under anesthesia every 2 to 3 weeks. Outcome Measure: Treatment success was defined as eradication of tumor without enucleation or external beam radiotherapy. Results: Significant therapeutic platinum levels were measured in the human tumors 2.5 and 5 hours after carboplatin administration. Increasing the temperature by 9°C for 15 minutes doubled platinum levels in the rabbit model. Of the 38 eyes with Reese-Ellsworth group 1 through 5b tumors that were treated primarily with thermochemotherapy, all 24 eyes with group 1 and 2 tumors were treated successfully and two of the 4 eyes with group 3 tumors and all 10 eyes with group 5b tumors were treated unsuccessfully. Chemoreduction plus SALT was the primary treatment in 35 eyes and was successful in all 10 eyes with group 1 through 4 tumors and unsuccessful in all 7 eyes with extensive subretinal seeding and all 18 eyes with group 5b tumors with vitreous seeding. Seventy patients received carboplatin or carboplatin, vincristine, and etoposide, with myelosuppression, occasionally associated with bacteremia, being the main side effect. Transfusions were required in 15% of patients. Radiation retinopathy occurred in all 6 eyes treated with iodine 125 plaques. Conclusions: Thermochemotherapy is successful primary treatment for Reese-Ellsworth group 1 and 2 retinoblastomas. For larger tumors in the absence of vitreous or extensive subretinal seeding, 3 cycles of chemoreduction followed by SALT eradicates residual viable tumor. Chemoreduction plus SALT was not successful in eyes with diffuse vitreous or extensive subretinal seeding. Prior chemotherapy increases the risk for radiation retinopathy following 125I plaque therapy. External beam radiotherapy can safely be avoided in the primary treatment of Reese-Ellsworth groups 1 through 4 nondispersed retinoblastoma. References 1. Eng C, Lin FP, Abramson DH, et al. Mortality from second tumors among long-term survivors of retinoblastoma . J Natl Cancer Inst . 1993;85:1121-1128.Crossref 2. MacFaul PA, Bedford MA. Ocular complications after therapeutic irradiation . Br J Opthalmol . 1970;54:237-247.Crossref 3. Imhof SM, Mourits MP, Hofman P, et al. Quantification of orbital and mid-facial growth retardation after megavoltage external beam irradiation in children with retinoblastoma . Ophthalmology . 1996;103:263-268.Crossref 4. Messmer EP, Sauerwein W, Heinrich T, et al. New and recurrent tumor foci following local treatment as well as external beam radiotherapy radiation in eyes of patients with hereditary retinoblastoma . Graefes Arch Clin Exp Ophthalmol . 1990;228:426-431.Crossref 5. White L. The role of chemotherapy in the treatment of retinoblastoma . Retina . 1983;3:194-199.Crossref 6. Haye C, Desjardins L, Elmaleh C, et al. Prognosis and treatment of retinoblastoma: 105 cases treated at Institut Curie . Ophthalmic Paediatr Genet . 1989;10:151-155.Crossref 7. Bin P, Boddy AV, English MW, et al. The comparative pharmacokinetics and pharmacodynamics of cisplatin and carboplatin in paediatric patients: a review . Anticancer Res . 1994;14;2279-2283. 8. Gaynon PS. Carboplatin in pediatric malignancies . Semin Oncol . 1994;21( (5 suppl 12) ):65-76. 9. Cairo MS. The use of ifosfamide, carboplatin, and etoposide in children with solid tumors . Semin Oncol . 1995;22( (3 suppl 7) ):23-27. 10. Lewis IJ, Strauss MC, Pearson A, Pinkerton CR, Stevens R. Phase II study of carboplatin in childhood tumors . Proc Am Soc Clin Oncol . 1993;12:A1413. Abstract. 11. Riccardi R, Riccardi A, DiRocco C, et al. Cerebrospinal fluid pharmacokinetics of carboplatin in children with brain tumors . Cancer Chemother Pharmacol . 1992;30:21.Crossref 12. Doz F, Neuenschwander S, Plantaz D, et al. Etoposide and carboplatin in extraocular retinoblastoma: a study by the Societe Francaise d'Oncologie Pediatrique . J Clin Oncol . 1995;13:902-909. 13. Hahn GM. Thermal enhancement of the actions of anticancer agents . In: GM Hahn, ed. Hyperthermia and Cancer . New York, NY: Plenum Publishing Corp; 1982:55-86. 14. Da Silva VF, Raaphorst GP, Goyal R, Feeley M. Drug cytotoxicity at elevated temperature: in vitro study on the U-87MG glioma cell line . J Neurosurg . 1987;67:885-888.Crossref 15. Herman TS, Teicher BA. Summary of studies adding systemic chemotherapy to local hyperthermia and radiation . Int J Hyperthermia . 1994;10:443-449.Crossref 16. Tapazoglu E, Cohen JD, Schmitt CL, Khatara A, Sapareto SA, Robins HI. Whole body hyperthermia and carboplatin: cytotoxicity for murine leukemia and normal marrow . Br J Cancer . 1991;64:528-530.Crossref 17. Murphree AL, Cote M, Gomer CJ. The evolution of photodynamic therapy techniques in the treatment of intraocular tumors . Photochem Photobiol . 1987;46:919-923.Crossref 18. Reed E, Sauerhoff S, Poirier MC. Quantitation of platinum-DNA binding in human tissues following therapeutic levels of drug exposure: a novel use of graphite furnace spectrometry . Atomic Spectroscopy . 1988;9:93-95. 19. Reed E, Ozols RF, Tarone R, Yuspa SH, Poirier MC. Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy . Proc Natl Acad Sci U S A . 1987;84:5024-5028.Crossref 20. McCormick B, Ellsworth R, Abramson D, Losasso T, Grabowski E. Results of external beam radiotherapy for children with retinoblastoma: a comparison of two techniques . J Pediatr Ophthalmol Strabismus . 1989;26:239-243. 21. Kinyoun JL, Zamber RW, Lawrence BS, Barlow WE, Arnold AM. Photocoagulation treatment for clinically significant radiation macular oedema . Br J Ophthalmol . 1995;79:144-149.Crossref 22. Elsas T, Thorud E, Jetne V, Conradi IS. Retinopathy after low dose irradiation for an intracranial tumor of the frontal lobe: a case report . Acta Ophthalmol . 1988;66:65-68.Crossref 23. Amoaku WM, Archer DB. Cephalic radiation and retinal vasculopathy . Eye . 1990;4:195-203.Crossref 24. Archer DB, Amoaku WM, Gardiner TA. Radiation retinopathy: clinical, histopathological, ultrastructural and experimental correlations . Eye . 1991;5:239-251.Crossref 25. O'Brien ME, Tonge K, Blake P, Moskovic E, Wiltshaw E. Blindness associated with high-dose carboplatin . Lancet . 1992;339:558.Crossref 26. Rankin EM, Pitts JF. Ophthalmic toxicity during carboplatin therapy . Ann Oncol . 1993;4:337-338. 27. Winick NJ, McKenna RW, Shuster JJ, et al. Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide . J Clin Oncol . 1993;11:209-217. 28. Tucker MA, Meadows AT, Boice JD Jr, et al. Cancer risk following treatment of childhood cancer . In: Boice JD Jr, Fraumeni JF Jr, eds. Radiation Carcinogenesis, Epidemiology and Biological Significance . New York, NY: Raven Press; 1984:211-224. 29. Wolter JR. Growth retardation of the orbital region after radiation treatment of retinoblastoma: causing a very typical physiognomy . J Pediatr Ophthalmol Strabismus . 1974;11:125-128. 30. Gallie BL, Budning A, DeBoer G, et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy . Arch Ophthalmol . 1996;114:1321-1328.Crossref

Journal

Archives of Ophthalmology – American Medical Association

Published: Nov 1, 1996

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