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Principles and Complications of Chemotherapy

  • Stacey ZahlerEmail author
  • Nicola G. Ghazi
  • Arun D. Singh
Chapter

Abstract

One of the most essential methods of treating cancer is with cytotoxic chemotherapy. Several primary and secondary ophthalmologic cancers exist that benefit from treatment with chemotherapy. Most chemotherapy drugs have nonselective mechanisms of action against DNA, RNA, proteins, or metabolic pathways in tumor cells, but because of the nonselective properties of chemotherapy, normal cells are also affected. Chemotherapy is often given in combination with other agents to enhance cytotoxic effects, combat multidrug resistance, and reduce risk of relapse. Chemotherapy is given in repetitive cycles at maximum tolerated doses in order to allow for a constant fraction of tumor cell kill and to allow for recovery of affected normal cells. Antineoplastic drugs have the narrowest therapeutic window of any class of drugs, so the treating physician must balance the risk of toxicities against the risk of relapse in choosing chemotherapy regimens for patients with ophthalmologic cancers. This chapter will discuss the basic principles of cytotoxic chemotherapy, review some of the commonly used treatment regimens of ophthalmologic cancers, and review common toxicities of chemotherapy.

Keywords

Cytotoxic chemotherapy Antineoplastic agents Intra-arterial chemotherapy Adjuvant therapy Neoadjuvant therapy Retinoblastoma Melanoma Rhabdomyosarcoma Orbital lymphoma 

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References

  1. 1.
    Poplack DG, Pizzo PA, editors. Principles and practice of pediatric oncology. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.Google Scholar
  2. 2.
    Pui CH, Evans WE. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol. 2013;50(3):185–96.CrossRefGoogle Scholar
  3. 3.
    Alley MC, Scudiero DA, Monks A, et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988;48(3):589–601.PubMedGoogle Scholar
  4. 4.
    Pommier Y. DNA topoisomerase I and II in cancer chemotherapy: update and perspectives. Cancer Chemother Pharmacol. 1993;32(2):103–8.CrossRefGoogle Scholar
  5. 5.
    Gerson SL, Bulgar AD, Weeks LD, et al. Alkylating Agents. In: Chabner BA, Longo DL, editors. Cancer chemotherapy and biotherapy: principles and practice. 5th ed. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer business; 2011. p. 267–92.Google Scholar
  6. 6.
    Harstrick A, Gonzales A, Schleucher N, et al. Comparison between short or long exposure to 5-fluorouracil in human gastric and colon cancer cell lines: biochemical mechanism of resistance. Anti-Cancer Drugs. 1998;9(7):625–34.CrossRefGoogle Scholar
  7. 7.
    Frei E 3rd, Canellos GP. Dose: a critical factor in cancer chemotherapy. Am J Med. 1980;69(4):585–94.CrossRefGoogle Scholar
  8. 8.
    Havrilesky LJ, Reiner M, Morrow PK, et al. A review of relative dose intensity and survival in patients with metastatic solid tumors. Crit Rev Oncol Hematol. 2015;93(3):203–10.CrossRefGoogle Scholar
  9. 9.
    Womer RB, West DC, Krailo MD, et al. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(33):4148–54.CrossRefGoogle Scholar
  10. 10.
    Kivisto KT, Kroemer HK, Eichelbaum M. The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions. Br J Clin Pharmacol. 1995;40(6):523–30.CrossRefGoogle Scholar
  11. 11.
    Goldie JH, Coldman AJ. Drug resistance in cancer: models and mechanisms. New York: Cambridge University Press; 1998. (digital version 2009). 247 p.CrossRefGoogle Scholar
  12. 12.
    Vadlapatla RK, Vadlapudi AD, Pal D, et al. Mechanisms of drug resistance in cancer chemotherapy: coordinated role and regulation of efflux transporters and metabolizing enzymes. Curr Pharm Des. 2013;19(40):7126–40.CrossRefGoogle Scholar
  13. 13.
    Eckardt AM, Lemound J, Rana M, et al. Orbital lymphoma: diagnostic approach and treatment outcome. World J Surg Oncol. 2013;11:73.CrossRefGoogle Scholar
  14. 14.
    Nathan FE, Berd D, Sato T, et al. BOLD+interferon in the treatment of metastatic uveal melanoma: first report of active systemic therapy. J Exp Clin Cancer Res CR. 1997;16(2):201–8.PubMedGoogle Scholar
  15. 15.
    Kivela T, Suciu S, Hansson J, et al. Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer (Oxford, England : 1990). 2003;39(8):1115–20.CrossRefGoogle Scholar
  16. 16.
    Schmittel A, Schmidt-Hieber M, Martus P, et al. A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma. Ann Oncol Off J Eur Soc Med Oncol. 2006;17(12):1826–9.CrossRefGoogle Scholar
  17. 17.
    Hughes MS, Zager J, Faries M, et al. Results of a randomized controlled multicenter phase III trial of percutaneous hepatic perfusion compared with best available care for patients with melanoma liver metastases. Ann Surg Oncol. 2016;23(4):1309–19.CrossRefGoogle Scholar
  18. 18.
    Leyvraz S, Piperno-Neumann S, Suciu S, et al. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol Off J Eur Soc Med Oncol. 2014;25(3):742–6.CrossRefGoogle Scholar
  19. 19.
    Carvajal RD, Sosman JA, Quevedo JF, et al. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014;311(23):2397–405.CrossRefGoogle Scholar
  20. 20.
    Flaherty LE, Unger JM, Liu PY, et al. Metastatic melanoma from intraocular primary tumors: the Southwest Oncology Group experience in phase II advanced melanoma clinical trials. Am J Clin Oncol. 1998;21(6):568–72.CrossRefGoogle Scholar
  21. 21.
    Sacco JJ, Kalirai H, Kenyani J, et al. Recent breakthroughs in metastatic uveal melanoma: a cause for optimism? Future Oncol (London, England). 2018;14(14):1335–8.Google Scholar
  22. 22.
    Broaddus E, Topham A, Singh AD. Incidence of retinoblastoma in the USA: 1975-2004. Br J Ophthalmol. 2009;93(1):21–3.CrossRefGoogle Scholar
  23. 23.
    Chung CY, Medina CA, Aziz HA, et al. Retinoblastoma: evidence for stage-based chemotherapy. Int Ophthalmol Clin. 2015;55(1):63–75.CrossRefGoogle Scholar
  24. 24.
    Brennan RC, Qaddoumi I, Billups CA, et al. Comparison of high-risk histopathological features in eyes with primary or secondary enucleation for retinoblastoma. Br J Ophthalmol. 2015;99(10):1366–71.CrossRefGoogle Scholar
  25. 25.
    Chantada GL, Dunkel IJ, de Davila MT, et al. Retinoblastoma patients with high risk ocular pathological features: who needs adjuvant therapy? Br J Ophthalmol. 2004;88(8):1069–73.CrossRefGoogle Scholar
  26. 26.
    Gobin YP, Dunkel IJ, Marr BP, et al. Combined, sequential intravenous and intra-arterial chemotherapy (bridge chemotherapy) for young infants with retinoblastoma. PLoS One. 2012;7(9):e44322.CrossRefGoogle Scholar
  27. 27.
    Hu HM, Zhang WL, Wang YZ, et al. Clinical features, treatment and prognosis of retinoblastoma in distant metastasis stage. Zhonghua Yan Ke Za Zhi [Chin J Ophthalmol]. 2017;53(2):121–7.Google Scholar
  28. 28.
    Dunkel IJ, Chan HS, Jubran R, et al. High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma. Pediatr Blood Cancer. 2010;55(1):149–52.PubMedGoogle Scholar
  29. 29.
    Dunkel IJ, Khakoo Y, Kernan NA, et al. Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma. Pediatr Blood Cancer. 2010;55(1):55–9.PubMedGoogle Scholar
  30. 30.
    Jabbour P, Chalouhi N, Tjoumakaris S, et al. Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr. 2012;10(3):175–81.CrossRefGoogle Scholar
  31. 31.
    Shields CL, Alset AE, Say EA, et al. Retinoblastoma control with primary intra-arterial chemotherapy: outcomes before and during the intravitreal chemotherapy era. J Pediatr Ophthalmol Strabismus. 2016;53(5):275–84.CrossRefGoogle Scholar
  32. 32.
    Shields CL, Jorge R, Say EA, et al. Unilateral retinoblastoma managed with intravenous chemotherapy versus intra-arterial chemotherapy. Outcomes based on the international classification of retinoblastoma. Asia-Pacific J Ophthalmol. 2016;5(2):97–103.CrossRefGoogle Scholar
  33. 33.
    Shields CL, Kaliki S, Al-Dahmash S, et al. Management of advanced retinoblastoma with intravenous chemotherapy then intra-arterial chemotherapy as alternative to enucleation. Retina. 2013;33(10):2103–9.CrossRefGoogle Scholar
  34. 34.
    Shields CL, Lally SE, Leahey AM, et al. Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Curr Opin Ophthalmol. 2014;25(5):374–85.CrossRefGoogle Scholar
  35. 35.
    Shields CL, Manjandavida FP, Lally SE, et al. Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma. Ophthalmology. 2014;121(7):1453–60.CrossRefGoogle Scholar
  36. 36.
    Shields CL, Shields JA. Intra-arterial chemotherapy for retinoblastoma. JAMA ophthalmology. 2016;134:1201.CrossRefGoogle Scholar
  37. 37.
    Abramson DH, Marr BP, Dunkel IJ, et al. Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results. Br J Ophthalmol. 2012;96(4):499–502.CrossRefGoogle Scholar
  38. 38.
    Gobin YP, Dunkel IJ, Marr BP, et al. Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience. Arch Ophthalmol. 2011;129(6):732–7.CrossRefGoogle Scholar
  39. 39.
    Ghassemi F, Shields CL, Ghadimi H, et al. Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma. JAMA Ophthalmol. 2014;132(8):936–41.CrossRefGoogle Scholar
  40. 40.
    Lawson BM, Saktanasate J, Say EA, et al. Intravitreal chemotherapy provides control for massive vitreous seeding from retinoblastoma. J Pediatr Ophthalmol Strabismus 2014;51 Online:e92–4.Google Scholar
  41. 41.
    Shields CL, Fulco EM, Arias JD, et al. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Eye. 2013;27(2):253–64.CrossRefGoogle Scholar
  42. 42.
    Shields CL, Manjandavida FP, Arepalli S, et al. Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds: preliminary results. JAMA Ophthalmol. 2014;132(3):319–25.CrossRefGoogle Scholar
  43. 43.
    Joshi D, Anderson JR, Paidas C, et al. Age is an independent prognostic factor in rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Pediatr Blood Cancer. 2004;42(1):64–73.CrossRefGoogle Scholar
  44. 44.
    Meza JL, Anderson J, Pappo AS, et al. Analysis of prognostic factors in patients with nonmetastatic rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: the Children’s Oncology Group. J Clin Oncol. 2006;24(24):3844–51.CrossRefGoogle Scholar
  45. 45.
    Oberlin O, Rey A, Lyden E, et al. Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European cooperative groups. J Clin Oncol. 2008;26(14):2384–9.CrossRefGoogle Scholar
  46. 46.
    Weigel BJ, Lyden E, Anderson JR, et al. Intensive multiagent therapy, including dose-compressed cycles of Ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation, in patients with high-risk rhabdomyosarcoma: a report from the Children’s Oncology Group. J Clin Oncol. 2016;34(2):117–22.CrossRefGoogle Scholar
  47. 47.
    Borinstein SC, Steppan D, Hayashi M, et al. Consensus and controversies regarding the treatment of rhabdomyosarcoma. Pediatr Blood Cancer. 2018;65(2)Google Scholar
  48. 48.
    al-Tweigeri T, Nabholtz JM, Mackey JR. Ocular toxicity and cancer chemotherapy. A review. Cancer. 1996;78(7):1359–73.CrossRefGoogle Scholar
  49. 49.
    Kawano T, Shigehira M, Uto H, et al. Retinal complications during interferon therapy for chronic hepatitis C. Am J Gastroenterol. 1996;91(2):309–13.PubMedGoogle Scholar
  50. 50.
    Esmaeli B, Amin S, Valero V, et al. Prospective study of incidence and severity of epiphora and canalicular stenosis in patients with metastatic breast cancer receiving docetaxel. J Clin Oncol. 2006;24(22):3619–22.CrossRefGoogle Scholar
  51. 51.
    Schmid KE, Kornek GV, Scheithauer W, et al. Update on ocular complications of systemic cancer chemotherapy. Surv Ophthalmol. 2006;51(1):19–40.CrossRefGoogle Scholar
  52. 52.
    Zinchuk O, Watanabe M, Hayashi N, et al. A case of tamoxifen keratopathy. Arch Ophthalmol. 2006;124(7):1046–8.CrossRefGoogle Scholar
  53. 53.
    Hazin R, Abuzetun JY, Daoud YJ, et al. Ocular complications of cancer therapy: a primer for the ophthalmologist treating cancer patients. Curr Opin Ophthalmol. 2009;20(4):308–17.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Stacey Zahler
    • 1
    Email author
  • Nicola G. Ghazi
    • 2
    • 3
  • Arun D. Singh
    • 4
  1. 1.Department of Pediatric Hematology, Oncology and Blood & Marrow TransplantationCleveland Clinic Children’s HospitalClevelandUSA
  2. 2.Division of Ophthalmology and Vitreoretinal ServiceKing Khaled Eye Specialist HospitalRiyadhSaudi Arabia
  3. 3.Department of OphthalmologyThe University of VirginiaCharlottesvilleUSA
  4. 4.Department of Ophthalmic OncologyCole Eye Institute, Cleveland ClinicClevelandUSA

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