Adrenocortical carcinoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Mohammed Abdelwahed M.D[3]

Overview

Chemotherapy and hormonal therapy may be required in the treatment of adrenocortical carcinoma. Mitotane is the only approved drug in the USA until now. Mitotane causes a destruction of the inner zones of the adrenal cortex, the zona fasciculata, and zona reticularis. Other drugs such as ketoconazole, metyrapone, aminoglutethimide, Etomidate, and Mifepristone can be used also. Target therapy such as sunitinib is IGF-1R antagonists that may be effective also.

Medical Therapy

Chemotherapy and hormonal therapy

Regimens typically include the drug mitotane, an inhibitor of steroid synthesis and toxic to cells of the adrenal cortex,[1] as well as standard cytotoxic drugs. One widely used regimen consists of cisplatin, doxorubicin, etoposide, and mitotane. The endocrine cell toxin streptozotocin has also been included in some treatment protocols. Chemotherapy may be given to patients with non-resectable disease, to shrink the tumor prior to surgery (neoadjuvant chemotherapy), or in an attempt to eliminate microscopic residual disease after surgery(adjuvant chemotherapy).

Steroid synthesis inhibitors such as aminoglutethimide may be used in a palliative manner to reduce the symptoms of hormonal syndromes. The overall response to chemotherapeutic regimens is 30% and 50%.

Mitotane

Indications
Side effects
Side effect Frequency Treatment
Nausea, vomiting, and diarrhea Very common Supportive therapy
Drug-induced hepatitis Rare Stop mitotane
Adrenal insufficiency Very common Start hydrocortisone with

mitotane and may use fludrocortisone

Hypogonadism Common Initiate testosterone replacement
Hypothyroidism Common Initiate thyroid hormone replacement
Increased SHBG, low TSH, low free

T4

Very common None

Target therapy

References

  1. Laurence L. Brunton, editor-in-chief; John S. Lazo and Keith L. Parker, Associate Editors (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th Edition. United States of America: The McGraw-Hill Companies, Inc. ISBN 0-07-142280-3.  line feed character in |author= at position 38 (help)
  2. Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobkin M; et al. (2005). "Management of patients with adrenal cancer: recommendations of an international consensus conference.". Endocr Relat Cancer. 12 (3): 667–80. PMID 16172199. doi:10.1677/erc.1.01029. 
  3. Schteingart DE, Sinsheimer JE, Counsell RE, Abrams GD, McClellan N, Djanegara T; et al. (1993). "Comparison of the adrenalytic activity of mitotane and a methylated homolog on normal adrenal cortex and adrenal cortical carcinoma.". Cancer Chemother Pharmacol. 31 (6): 459–66. PMID 8453685. 
  4. Cai W, Counsell RE, Schteingart DE, Sinsheimer JE, Vaz AD, Wotring LL (1997). "Adrenal proteins bound by a reactive intermediate of mitotane.". Cancer Chemother Pharmacol. 39 (6): 537–40. PMID 9118466. doi:10.1007/s002800050610. 
  5. Cai W, Counsell RE, Schteingart DE, Sinsheimer JE, Vaz AD, Wotring LL (1997). "Adrenal proteins bound by a reactive intermediate of mitotane.". Cancer Chemother Pharmacol. 39 (6): 537–40. PMID 9118466. doi:10.1007/s002800050610. 
  6. Volante M, Terzolo M, Fassnacht M, Rapa I, Germano A, Sbiera S; et al. (2012). "Ribonucleotide reductase large subunit (RRM1) gene expression may predict efficacy of adjuvant mitotane in adrenocortical cancer.". Clin Cancer Res. 18 (12): 3452–61. PMID 22547773. doi:10.1158/1078-0432.CCR-11-2692. 
  7. Hartzband PI, Van Herle AJ, Sorger L, Cope D (1988). "Assessment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction: comparison of ACTH stimulation, insulin-hypoglycemia and metyrapone.". J Endocrinol Invest. 11 (11): 769–76. PMID 2852194. doi:10.1007/BF03350221. 
  8. Santen RJ, Wells SA, Runić S, Gupta C, Kendall J, Rudy EB; et al. (1977). "Adrenal suppression with aminoglutethimide. I. Differential e-fects of aminoglutethimide on glucocorticoid metabolism as a rationale for use of hydrocortisone.". J Clin Endocrinol Metab. 45 (3): 469–79. PMID 198423. doi:10.1210/jcem-45-3-469. 
  9. Drake WM, Perry LA, Hinds CJ, Lowe DG, Reznek RH, Besser GM (1998). "Emergency and prolonged use of intravenous etomidate to control hypercortisolemia in a patient with Cushing's syndrome and peritonitis.". J Clin Endocrinol Metab. 83 (10): 3542–4. PMID 9768661. doi:10.1210/jcem.83.10.5156. 
  10. Flack MR, Pyle RG, Mullen NM, Lorenzo B, Wu YW, Knazek RA; et al. (1993). "Oral gossypol in the treatment of metastatic adrenal cancer.". J Clin Endocrinol Metab. 76 (4): 1019–24. PMID 8473376. doi:10.1210/jcem.76.4.8473376. 
  11. Kroiss M, Quinkler M, Johanssen S, van Erp NP, Lankheet N, Pöllinger A; et al. (2012). "Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial.". J Clin Endocrinol Metab. 97 (10): 3495–503. PMID 22837187. doi:10.1210/jc.2012-1419. 
  12. Zhang Q, Pan J, Lubet RA, Wang Y, You M (2015). "Targeting the insulin-like growth factor-1 receptor by picropodophyllin for lung cancer chemoprevention.". Mol Carcinog. 54 Suppl 1: E129–37. PMID 25163779. doi:10.1002/mc.22206. 
  13. Naing A, LoRusso P, Fu S, Hong DS, Anderson P, Benjamin RS; et al. (2012). "Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors.". Clin Cancer Res. 18 (9): 2625–31. PMC 3875297Freely accessible. PMID 22465830. doi:10.1158/1078-0432.CCR-12-0061. 

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