En el carcinoma suprarrenal metastásico no existen esquemas de tratamiento aprobados tras la progresión a una primera línea de quimioterapia/mitotane, si bien un alto porcentaje de pacientes son candidatos a recibirlos. En este artículo realizamos una revisión sobre las posibles alternativas terapéuticas tras la progresión a una primera línea de tratamiento en pacientes con carcinoma suprarrenal metastásico. A propósito de la misma, se presenta un caso clínico en el que se consigue una prolongada supervivencia global, mucho mayor de la esperable, probablemente debido al manejo multidisciplinario del caso y a la utilización de la mayor parte del arsenal terapéutico disponible.

Autores: Luis Cabezón-Gutiérrez[1], Parham Khosravi-Shahi[1], Sara Custodio-Cabello[1], David Ricardo Lujan-Rodríguez[2], Jesús Ángel Garijo-Álvarez[3], Claudia María Causso-Lariena[4], Ana Isabel Franco-Moreno[5]

Affiliation:
[1] Departamento de Oncología, Hospital Universitario de Torrejón, Madrid, España
[2] Departamento de Anatomía Patológica, Hospital Universitario de Torrejón, Madrid, España
[3] Departamento de Cirugía General, Hospital Universitario de Torrejón, Madrid, España
[4] Departamento de Endocrinología, Hospital Universitario de Torrejón, Madrid, España
[5] Departamento de Endocrinología, Hospital Universitario de Torrejón, Madrid, España

E-mail: lcabezon@torrejonsalud.com

Author address:
[1] Calle Mateo Inurria sin número
Torrejón de Ardoz
CP 28850
Madrid
España

Citation: Cabezón-Gutiérrez L, Khosravi-Shahi P, Custodio-Cabello S, Lujan-Rodríguez DR, Garijo-Álvarez JA, Causso-Lariena CM, et al. Palliative chemotherapy in metastatic adrenal carcinoma beyond the first line: a case report and literature review. Medwave 2017 Jul;17(6):7007 doi: 10.5867/medwave.2017.06.7007

Submission date: 8/5/2017

Acceptance date: 15/7/2017

Publication date: 31/7/2017

Origin: not requested

Type of review: reviewed by five external peer reviewers, double-blind

PubMed record

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1. Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World J Surg. 2006 May;30(5):872-8. | PubMed |
2. Bilimoria KY, Shen WT, Elaraj D, Bentrem DJ, Winchester DJ, Kebebew E, et al. Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer. 2008 Dec 1;113(11):3130-6. | CrossRef | PubMed |
3. Kerkhofs TM, Verhoeven RH, Van der Zwan JM, Dieleman J, Kerstens MN, Links TP, et al. Adrenocortical carcinoma: a population-based study on incidence and survival in the Netherlands since 1993. Eur J Cancer. 2013 Jul;49(11):2579-86. | CrossRef | PubMed |
4. Burotto M, Tageja N, Rosenberg A, Mahalingam S, Quezado M, Velarde M, et al. Brain metastasis in patients with adrenocortical carcinoma: a clinical series. J Clin Endocrinol Metab. 2015 Feb;100(2):331-6. | CrossRef | PubMed |
5. Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, et al. Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res. 2009 Jan 15;15(2):668-76. | CrossRef | PubMed |
6. Assié G, Letouzé E, Fassnacht M, Jouinot A, Luscap W, Barreau O, et al. Integrated genomic characterization of adrenocortical carcinoma. Nat Genet. 2014 Jun;46(6):607-12. | CrossRef | PubMed |
7. Dackiw AP, Lee JE, Gagel RF, Evans DB. Adrenal cortical carcinoma. World J Surg. 2001 Jul;25(7):914-26. | PubMed |
8. Bertagna C, Orth DN. Clinical and laboratory findings and results of therapy in 58 patients with adrenocortical tumors admitted to a single medical center (1951 to 1978). Am J Med. 1981 Nov;71(5):855-75. | PubMed |
9. Luton JP, Cerdas S, Billaud L, Thomas G, Guilhaume B, Bertagna X, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med. 1990 Apr 26;322(17):1195-201. | PubMed |
10. Gröndal S, Cedermark B, Eriksson B, Grimelius L, Harach R, Kristoffersson A, et al. A retrospective study of a rare tumor with a poor prognosis. Eur J Surg Oncol. 1990 Dec;16(6):500-6. | PubMed |
11. Hogan TF, Gilchrist KW, Westring DW, Citrin DL. A clinical and pathological study of adrenocortical carcinoma: therapeutic implications. Cancer. 1980 Jun 1;45(11):2880-3. | PubMed |
12. Wajchenberg BL, Albergaria Pereira MA, Medonca BB, Latronico AC, Campos Carneiro P, Alves VA, et al. Adrenocortical carcinoma: clinical and laboratory observations. Cancer. 2000 Feb 15;88(4):711-36. | PubMed |
13. Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobkin M, et al. Management of patients with adrenal cancer: recommendations of an international consensus conference. Endocr Relat Cancer. 2005 Sep;12(3):667-80. | PubMed |
14. Stojadinovic A, Brennan MF, Hoos A, Omeroglu A, Leung DH, Dudas ME, et al. Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis. Mod Pathol. 2003 Aug;16(8):742-51. | PubMed |
15. Malandrino P, Al Ghuzlan A, Castaing M, Young J, Caillou B, Travagli JP, et al. Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma. Endocr Relat Cancer. 2010 Aug 16;17(3):797-807. | CrossRef | PubMed |
16. Haak HR, Hermans J, van de Velde CJ, Lentjes EG, Goslings BM, Fleuren GJ, et al. Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients. Br J Cancer. 1994 May;69(5):947-51. | PubMed |
17. Heilmann P, Wagner P, Nawroth PP, Ziegler R. [Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels]. Med Klin (Munich). 2001 Jul 15;96(7):371-7. | PubMed |
18. Pommier RF, Brennan MF. An eleven-year experience with adrenocortical carcinoma. Surgery. 1992 Dec;112(6):963-70; discussion 970-1. | PubMed |
19. Williamson SK, Lew D, Miller GJ, Balcerzak SP, Baker LH, Crawford ED. Phase II evaluation of cisplatin and etoposide followed by mitotane at disease progression in patients with locally advanced or metastatic adrenocortical carcinoma: a Southwest Oncology Group Study. Cancer. 2000 Mar 1;88(5):1159-65. | PubMed |
20. Berruti A, Terzolo M, Sperone P, Pia A, Della Casa S, Gross DJ, et al. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005 Sep;12(3):657-66. | PubMed |
21. Khan TS, Imam H, Juhlin C, Skogseid B, Gröndal S, Tibblin S, et al. Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use. Ann Oncol. 2000 Oct;11(10):1281-7. | PubMed |
22. Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. | CrossRef | PubMed |
23. Sperone P, Ferrero A, Daffara F, Priola A, Zaggia B, Volante M, et al. Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study. Endocr Relat Cancer. 2010 Apr 21;17(2):445-53. | CrossRef | PubMed |
24. Kroiss M, Quinkler M, Johanssen S, van Erp NP, Lankheet N, Pöllinger A, et al. Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol Metab. 2012 Oct;97(10):3495-503. | CrossRef | PubMed |
25. Quinkler M, Hahner S, Wortmann S, Johanssen S, Adam P, Ritter C, et al. Treatment of advanced adrenocortical carcinoma with erlotinib plus gemcitabine. J Clin Endocrinol Metab. 2008 Jun;93(6):2057-62. | CrossRef | PubMed |
26. Haluska P, Worden F, Olmos D, Yin D, Schteingart D, Batzel GN, et al. Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma. Cancer Chemother Pharmacol. 2010 Mar;65(4):765-73. | CrossRef | PubMed |
27. Carden E. Kim S, Jones RL, Alam SM, Johnson FM, Stephens AW, Poondru S, et al. Phase I study of intermittent dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growthfactor-1 receptor (IGF-1R) and insulin receptor (IR) in patients with advanced solid tumors. J Clin Oncol 2010;28(Suppl.):15s [abstr 2530]. | CrossRef |
28. Fraenkel M, Gueorguiev M, Barak D, Salmon A, Grossman AB, Gross DJ. Everolimus therapy for progressive adrenocortical cancer. Endocrine. 2013 Aug;44(1):187-92. | CrossRef | PubMed |
29. Fassnacht M, Berruti A, Baudin E, Demeure MJ, Gilbert J, Haak H, et al. Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study. Lancet Oncol. 2015 Apr;16(4):426-35. | CrossRef | PubMed |
30. Wahab NA, Zainudin S, AbAziz A, Mustafa N, Sukor N, Kamaruddin NA. Multi-Target Approach to Metastatic Adrenal Cell Carcinoma. Arch Iran Med. 2016 Sep;19(9):671-3. | CrossRef | PubMed |

Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World J Surg. 2006 May;30(5):872-8. | PubMed |

Bilimoria KY, Shen WT, Elaraj D, Bentrem DJ, Winchester DJ, Kebebew E, et al. Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer. 2008 Dec 1;113(11):3130-6. | CrossRef | PubMed |

Kerkhofs TM, Verhoeven RH, Van der Zwan JM, Dieleman J, Kerstens MN, Links TP, et al. Adrenocortical carcinoma: a population-based study on incidence and survival in the Netherlands since 1993. Eur J Cancer. 2013 Jul;49(11):2579-86. | CrossRef | PubMed |

Burotto M, Tageja N, Rosenberg A, Mahalingam S, Quezado M, Velarde M, et al. Brain metastasis in patients with adrenocortical carcinoma: a clinical series. J Clin Endocrinol Metab. 2015 Feb;100(2):331-6. | CrossRef | PubMed |

Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, et al. Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res. 2009 Jan 15;15(2):668-76. | CrossRef | PubMed |

Assié G, Letouzé E, Fassnacht M, Jouinot A, Luscap W, Barreau O, et al. Integrated genomic characterization of adrenocortical carcinoma. Nat Genet. 2014 Jun;46(6):607-12. | CrossRef | PubMed |

Dackiw AP, Lee JE, Gagel RF, Evans DB. Adrenal cortical carcinoma. World J Surg. 2001 Jul;25(7):914-26. | PubMed |

Bertagna C, Orth DN. Clinical and laboratory findings and results of therapy in 58 patients with adrenocortical tumors admitted to a single medical center (1951 to 1978). Am J Med. 1981 Nov;71(5):855-75. | PubMed |

Luton JP, Cerdas S, Billaud L, Thomas G, Guilhaume B, Bertagna X, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med. 1990 Apr 26;322(17):1195-201. | PubMed |

Gröndal S, Cedermark B, Eriksson B, Grimelius L, Harach R, Kristoffersson A, et al. A retrospective study of a rare tumor with a poor prognosis. Eur J Surg Oncol. 1990 Dec;16(6):500-6. | PubMed |

Hogan TF, Gilchrist KW, Westring DW, Citrin DL. A clinical and pathological study of adrenocortical carcinoma: therapeutic implications. Cancer. 1980 Jun 1;45(11):2880-3. | PubMed |

Wajchenberg BL, Albergaria Pereira MA, Medonca BB, Latronico AC, Campos Carneiro P, Alves VA, et al. Adrenocortical carcinoma: clinical and laboratory observations. Cancer. 2000 Feb 15;88(4):711-36. | PubMed |

Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobkin M, et al. Management of patients with adrenal cancer: recommendations of an international consensus conference. Endocr Relat Cancer. 2005 Sep;12(3):667-80. | PubMed |

Stojadinovic A, Brennan MF, Hoos A, Omeroglu A, Leung DH, Dudas ME, et al. Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis. Mod Pathol. 2003 Aug;16(8):742-51. | PubMed |

Malandrino P, Al Ghuzlan A, Castaing M, Young J, Caillou B, Travagli JP, et al. Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma. Endocr Relat Cancer. 2010 Aug 16;17(3):797-807. | CrossRef | PubMed |

Haak HR, Hermans J, van de Velde CJ, Lentjes EG, Goslings BM, Fleuren GJ, et al. Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients. Br J Cancer. 1994 May;69(5):947-51. | PubMed |

Heilmann P, Wagner P, Nawroth PP, Ziegler R. [Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels]. Med Klin (Munich). 2001 Jul 15;96(7):371-7. | PubMed |

Pommier RF, Brennan MF. An eleven-year experience with adrenocortical carcinoma. Surgery. 1992 Dec;112(6):963-70; discussion 970-1. | PubMed |

Williamson SK, Lew D, Miller GJ, Balcerzak SP, Baker LH, Crawford ED. Phase II evaluation of cisplatin and etoposide followed by mitotane at disease progression in patients with locally advanced or metastatic adrenocortical carcinoma: a Southwest Oncology Group Study. Cancer. 2000 Mar 1;88(5):1159-65. | PubMed |

Berruti A, Terzolo M, Sperone P, Pia A, Della Casa S, Gross DJ, et al. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005 Sep;12(3):657-66. | PubMed |

Khan TS, Imam H, Juhlin C, Skogseid B, Gröndal S, Tibblin S, et al. Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use. Ann Oncol. 2000 Oct;11(10):1281-7. | PubMed |

Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. | CrossRef | PubMed |

Sperone P, Ferrero A, Daffara F, Priola A, Zaggia B, Volante M, et al. Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study. Endocr Relat Cancer. 2010 Apr 21;17(2):445-53. | CrossRef | PubMed |

Kroiss M, Quinkler M, Johanssen S, van Erp NP, Lankheet N, Pöllinger A, et al. Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol Metab. 2012 Oct;97(10):3495-503. | CrossRef | PubMed |

Quinkler M, Hahner S, Wortmann S, Johanssen S, Adam P, Ritter C, et al. Treatment of advanced adrenocortical carcinoma with erlotinib plus gemcitabine. J Clin Endocrinol Metab. 2008 Jun;93(6):2057-62. | CrossRef | PubMed |

Haluska P, Worden F, Olmos D, Yin D, Schteingart D, Batzel GN, et al. Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma. Cancer Chemother Pharmacol. 2010 Mar;65(4):765-73. | CrossRef | PubMed |

Carden E. Kim S, Jones RL, Alam SM, Johnson FM, Stephens AW, Poondru S, et al. Phase I study of intermittent dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growthfactor-1 receptor (IGF-1R) and insulin receptor (IR) in patients with advanced solid tumors. J Clin Oncol 2010;28(Suppl.):15s [abstr 2530]. | CrossRef |

Fraenkel M, Gueorguiev M, Barak D, Salmon A, Grossman AB, Gross DJ. Everolimus therapy for progressive adrenocortical cancer. Endocrine. 2013 Aug;44(1):187-92. | CrossRef | PubMed |

Fassnacht M, Berruti A, Baudin E, Demeure MJ, Gilbert J, Haak H, et al. Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study. Lancet Oncol. 2015 Apr;16(4):426-35. | CrossRef | PubMed |

Wahab NA, Zainudin S, AbAziz A, Mustafa N, Sukor N, Kamaruddin NA. Multi-Target Approach to Metastatic Adrenal Cell Carcinoma. Arch Iran Med. 2016 Sep;19(9):671-3. | CrossRef | PubMed |