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2011, Número 3

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Rev Mex Med Repro 2011; 3.4 (3)


Efecto de la quimioterapia y el cáncer testicular avanzado o el linfoma de Hodgkin en la integridad del ácido desoxirribonucleico del esperma

O’Flaherty C, Hales BF, Chan P, Robaire B

Idioma: Español
Referencias bibliográficas: 39
Paginas: 123-132
Archivo PDF: 178.05 Kb.


RESUMEN

Objetivo: determinar el efecto de la combinación de la quimioterapia en la calidad de los espermatozoides nuevos de pacientes con cáncer testicular avanzado y pacientes con linfoma de Hodgkin.
Diseño: estudio prospectivo longitudinal.
Ubicación: unidad académica.
Pacientes: pacientes con cáncer testicular metastásico de reciente diagnóstico y con linfoma de Hodgkin que requerían quimioterapia, en comparación con voluntarios sanos de la comunidad pareados por edad.
Intervención: ninguna.
Criterio de valoración primario: se compararon los parámetros seminales, concentraciones hormonales, volumen testicular y presencia de fragmentos de ADN en pacientes con cáncer y en voluntarios sanos de la comunidad, antes y después de la quimioterapia de los pacientes a los 6, 12, 18 y 24 meses.
Resultados: antes de la quimioterapia, ambos grupos de cáncer tuvieron mala calidad seminal en comparación con los voluntarios de la comunidad. Entre los pacientes con cáncer testicular y linfoma de Hodgkin, 67 y 60%, respectivamente, tuvieron ‹ 5 x 106 espermatozoides/mL a los seis meses después de la quimioterapia. A los 24 meses, 60 y 57% de los pacientes con cáncer testicular y linfoma de Hodgkin, respectivamente, tuvieron concentraciones espermáticas normales. La concentración de FSH fue significativamente más alta en el grupo de cáncer, en comparación con los voluntarios de la comunidad a los 6 y 12 meses después de la quimioterapia. Antes de la quimioterapia, el daño al ADN espermático fue mayor en el grupo de cáncer que en los voluntarios de la comunidad; este daño aumentó aún más a los seis meses y se mantuvo elevado 24 meses después del tratamiento.
Conclusiones: el esperma generado después de la quimioterapia mantuvo un grado significativo de daño a la cromatina. Por tanto, los supervivientes de cáncer testicular y linfoma de Hodgkin están en riesgo de tener un desenlace reproductivo anormal. Se recomienda abordar apropiadamente los riesgos reproductivos y la preservación de la fertilidad antes de la quimioterapia en estos pacientes.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Garner MJ, Turner MC, Ghadirian P, Krewski D. Epidemiology of testicular cancer: an overview. Int J Cancer 2005;116:331-339.

  2. Bray F, Richiardi L, Ekbom A, Pukkala E, et al. Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality. Int J Cancer 2006;118:3099-3111.

  3. Walsh TJ, Grady RW, Porter MP, Lin DW, Weiss NS. Incidence of testicular germ cell cancers in U.S. children: SEER program experience 1973 to 2000. Urology 2006;68:402-405.

  4. Huddart RA, Birtle AJ. Recent advances in the treatment of testicular cancer. Expert Rev Anticancer Ther 2005;5:123-138.

  5. Kopp HG, Kuczyk M, Classen J, Stenzl A, et al. Advances in the treatment of testicular cancer. Drugs 2006;66:641-659.

  6. Petersen PM, Hansen SW. The course of long-term toxicity in patients treated with cisplatin-based chemotherapy for nonseminomatous germ-cell cancer. Ann Oncol 1999;10:1475-1483.

  7. Gandini L, Sgro P, Lombardo F, Paoli D, et al. Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients. Hum Reprod 2006;21:2882-2889.

  8. Bieber AM, Marcon L, Hales BF, Robaire B. Effects of chemotherapeutic agents for testicular cancer on the male rat reproductive system, spermatozoa, and fertility. J Androl 2006;27:189-200.

  9. Vaisheva F, Delbes G, Hales BF, Robaire B. Effects of the chemotherapeutic agents for non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), on the male rat reproductive system and progeny outcome. J Androl 2007;28:578-587.

  10. Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril 2004;81:1289-1295.

  11. Marchetti F, Wyrobek AJ. Mechanisms and consequences of paternally-transmitted chromosomal abnormalities. Birth Defects Res C Embryo Today 2005;75:112-129.

  12. World Health Organization. Laboratory manual for examination of human semen and semen-cervical mucus interaction. 2nd ed. Cambridge: The Press Syndicate of the University of Cambridge, 1987:3-27.

  13. Evenson DP, Jost LK, Marshall D, Zinaman MJ, et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod 1999;14:1039-1049.

  14. Spano M, Bonde JP, Hjollund HI, Kolstad HA, et al. Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team. Fertil Steril 2000;73:43-50.

  15. Payne JF, Raburn DJ, Couchman GM, Price TM, et al. Redefining the relationship between sperm deoxyribonucleic acid fragmentation as measured by the sperm chromatin structure assay and outcomes of assisted reproductive techniques. Fertil Steril 2005;84:356-364.

  16. O’FlahertyC, Vaisheva F, Hales BF, Chan P, Robaire B. Characterization of sperm chromatin quality in testicular cancer and Hodgkin’s lymphoma patients prior to chemotherapy. Hum Reprod 2008;23:1044-1052.

  17. Williams SD, Birch R, Einhorn LH, Irwin L, et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987;316:1435-1440.

  18. Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B. Study. J Clin Oncol 1998;16:1287-1293.

  19. Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant Hodgkin’s disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother Pharmacol 1979;2:101-105.

  20. Canellos GP, Anderson JR, Propert KJ, Nissen N, et al. Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992;327:1478-1484.

  21. Andrieu JM, Colonna P. Are ABVD and MOPP/ABV truly equivalent for treating Hodgkin’s disease at advanced stages? J Clin Oncol 1998;16:2283b.

  22. Kruger TF, Ackerman SB, Simmons KF, Swanson RJ, et al. A quick, reliable staining technique for human sperm morphology. Arch Androl 1987;18:275-277.

  23. Haines G, Marples B, Daniel P, Morris I. DNA damage in human and mouse spermatozoa after in vitro–irradiation assessed by the comet assay. Adv Exp Med Biol 1998;444:79-91.

  24. Codrington AM, Hales BF, Robaire B. Exposure of male rats to cyclophosphamide alters the chromatin structure and basic proteome in spermatozoa. Hum Reprod 2007;22:1431-1442.

  25. Howell SJ, Shalet SM. Testicular function following chemotherapy. Hum Reprod Update 2001;7:363-369.

  26. Kobayashi H, Larson K, Sharma RK, Nelson DR, et al. DNA damage in patients with untreated cancer as measured by the sperm chromatin structure assay. Fertil Steril 2001;75:469-475.

  27. Petersen PM, Skakkebaek NE, Vistisen K, Rorth M, Giwercman A. Semen quality and reproductive hormones before orchiectomy in men with testicular cancer. J Clin Oncol 1999;17:941-947.

  28. Delbes G, Hales BF, Robaire B. Effects of the chemotherapy cocktail used to treat testicular cancer on sperm chromatin integrity. J Androl 2007;28:241-249.

  29. Marcon L, Hales BF, Robaire B. Reversibility of the effects of subchronic exposure to the cancer chemotherapeutics bleomycin, etoposide, and cisplatin on spermatogenesis, fertility, and progeny outcome in the male rat. J Androl 2008;29:408-417.

  30. Howell SJ, Radford JA, Ryder WD, Shalet SM. Testicular function after cytotoxic chemotherapy: evidence of Leydig cell insufficiency. J Clin Oncol 1999;17:1493-1498.

  31. Gerl A, Muhlbayer D, Hansmann G, Mraz W, Hiddemann W. The impact of chemotherapy on Leydig cell function in long term survivors of germ cell tumors. Cancer 2001;91:1297-1303.

  32. Spermon JR, Ramos L, Wetzels AM, Sweep CG, et al. Sperm integrity pre-and post-chemotherapy in men with testicular germ cell cancer. Hum Reprod 2006;21:1781-1786.

  33. Howell SJ, Shalet SM. Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr 2005;34:12-17.

  34. Delbes G, Chan D, Pakarinen P, Trasler JM, et al. Impact of the chemotherapy cocktail used to treat testicular cancer on the gene expression profile of germ cells from male brown-Norway rats. Biol Reprod 2008;80:320-327.

  35. Heller CG, Clermont Y. Spermatogenesis in man: an estimate of its duration. Science 1963;140:184-186.

  36. Poirier MC, Reed E, Litterst CL, Katz D, Gupta-Burt S. Persistence of platinum-ammine-DNA adducts in gonads and kidneys of rats and multiple tissues from cancer patients. Cancer Res 1992;52:149-153.

  37. van Delft JHM, van den Ende AMC, Keizer HJ, Ouwerkerk J, Baan RA. Determination of N7-methylguanine in DNA of white blood cells from cancer patients treated with dacarbazine1. Carcinogenesis 1992;13:1257-1259.

  38. Tempest HG, Ko E, Chan P, Robaire B, et al. Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin’s lymphoma patients. Hum Reprod 2007;23:251-258.

  39. Frias S, Van HP, Meistrich ML, Lowe XR, et al. NOVP chemotherapy for Hodgkin’s disease transiently induces sperm aneuploidies associated with the major clinical aneuploidy syndromes involving chromosomes X, Y, 18, and 21. Cancer Res 2003;63:44-51.




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