Mitotane

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Mitotane
Mitotane.svg
Clinical data
Trade names Lysodren
AHFS/Drugs.com Monograph
MedlinePlus a608050
License data
Pregnancy
category
  • C
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 40%
Protein binding 6%
Biological half-life 18 to 159 days
Identifiers
Synonyms 1,1-(Dichlorodiphenyl)-2,2-dichloroethane; o,p'-DDD
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard 100.000.152
Chemical and physical data
Formula C14H10Cl4
Molar mass 320.04 g/mol
3D model (Jmol)
Chirality Racemic mixture
  (verify)

Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome.[1][2][3][4] It is a derivative of p,p'-DDT and an isomer of p,p'-DDD, and is also known as 1,1-(dichlorodiphenyl)-2,2-dichloroethane (o,p'-DDD).[5]

Medical uses[edit]

Mitotane has been produced by Bristol Myers Squibb SpA but it is marketed as an orphan drug for adrenocortical carcinoma due to the small number of patients in need of it. Its main use is in those patients who have persistent disease despite surgical resection, those who are not surgical candidates, or those who have metastatic disease. A 2007 study of 177 patients shows a significant increase in the recurrence-free interval after radical surgery followed by mitotane when compared to surgery alone.[6] The drug is also sometimes used in the treatment of Cushing's syndrome.[3]

Side effects[edit]

The use of mitotane is unfortunately limited by side effects,[7] which, as reported by Schteinberg et al., include anorexia and nausea (88%), diarrhea (38%), vomiting (23%), decreased memory and ability to concentrate (50%), rash (23%), gynecomastia (50%), arthralgia (19%), and leukopenia (7%).[8]

Pharmacology[edit]

Mitotane is an inhibitor of the adrenal cortex. It acts as an inhibitor of cholesterol side-chain cleavage enzyme (P450scc, CYP11A1), and also of 11β-hydroxylase (CYP11B1), 18-hydroxylase (aldosterone synthase, CYP11B2), and 3β-hydroxysteroid dehydrogenase (3β-HSD) to a lesser extent.[1][7] In addition, mitotane has direct and selective cytotoxic effects on the adrenal cortex, via an unknown mechanism, and thereby induces permanent adrenal atrophy similarly to DDD.[9][10]

History[edit]

Mitotane was introduced in 1960 for the treatment of adrenocortical carcinoma.[3]

Society and culture[edit]

Mitotane is the INN, USAN, BAN, and JAN of mitotane.[4][11]

Veterinary use[edit]

Mitotane is also used to treat Cushing's disease (pituitary-dependent Cushing's syndrome) in dogs. The medication is used in the controlled destruction of adrenal tissue, leading to a decrease in cortisol production.[12]

See also[edit]

References[edit]

  1. ^ a b J. Larry Jameson; Leslie J. De Groot (18 May 2010). Endocrinology - E-Book: Adult and Pediatric. Elsevier Health Sciences. pp. 1888–. ISBN 1-4557-1126-8. 
  2. ^ Hahner S, Fassnacht M (April 2005). "Mitotane for adrenocortical carcinoma treatment". Current opinion in investigational drugs (London, England : 2000). 6 (4): 386–94. PMID 15898346. 
  3. ^ a b c Marcello D. Bronstein (1 October 2010). Cushing's Syndrome: Pathophysiology, Diagnosis and Treatment. Springer Science & Business Media. pp. 156–. ISBN 978-1-60327-449-4. 
  4. ^ a b J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 382–. ISBN 978-1-4757-2085-3. 
  5. ^ Information from PubChem
  6. ^ Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A (2007). "Adjuvant mitotane treatment for adrenocortical carcinoma". N Engl J Med. 356 (23): 2372–2380. PMID 17554118. doi:10.1056/NEJMoa063360. 
  7. ^ a b Philip E. Harris; Pierre-Marc G. Bouloux (24 March 2014). Endocrinology in Clinical Practice, Second Edition. CRC Press. pp. 216–. ISBN 978-1-84184-951-5. 
  8. ^ Schteinberg DE, Motazedi A, NoonanRA, Thompson NW (1982). "Treatment of Adrenal Carcinomas". Arch.Surg. 117: 1142–1149. 
  9. ^ Eudocia Quant Lee, MD, MPH; David Schiff, MD; Patrick Y. Wen, MD (28 September 2011). Neurologic Complications of Cancer Therapy. Demos Medical Publishing. pp. 179–. ISBN 978-1-61705-019-0. 
  10. ^ C.R. Kannan (6 December 2012). The Adrenal Gland. Springer Science & Business Media. pp. 160–. ISBN 978-1-4613-1001-3. 
  11. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 697–. ISBN 978-3-88763-075-1. 
  12. ^ Canine Cushing’s Syndrome: Diagnosis and Treatment

External links[edit]