CHEMOTHERAPY OF ADRENOCORTICAL CANCER WITH o,p′DDD
Authors: Delbert M. Bergenstal, Roy Hertz, Mortimer B. Lipsett, Richard H. Moy
Journal: Annals of Internal Medicine (1960)

Article1 October 1960CHEMOTHERAPY OF ADRENOCORTICAL CANCER WITH o,p′DDDDELBERT M. BERGENSTAL, M.D., F.A.C.P., ROY HERTZ, M.D., F.A.C.P., MORTIMER B. LIPSETT, M.D., RICHARD H. MOY, M.D.DELBERT M. BERGENSTAL, M.D., F.A.C.P.Search for more papers by this author, ROY HERTZ, M.D., F.A.C.P.Search for more papers by this author, MORTIMER B. LIPSETT, M.D.Search for more papers by this author, RICHARD H. MOY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-53-4-672 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOur approach to the chemotherapy of adrenocortical carcinoma is based upon the original observations of Nelson and Woodard.1 They observed that the oral administration to dogs of the insecticide, DDD, or Rothane, induced a selective necrosis of the zona fasciculata and zona reticularis of the adrenal cortex. Nichols and his associates2, 3 pursued this finding and demonstrated that adrenal cortical function was markedly diminished in dogs so treated. However, early attempts to apply this adrenocorticolytic effect in man were unsuccessful.4, 5, 6Further exploration of the therapeutic potential of this compound was made possible by the observations that a contaminant...Bibliography1. NelsonWoodard AAG: Severe adrenal cortical atrophy (cytotoxic) and hepatic damage produced in dogs by feeding 2,2-bis(parachlorophenyl)-1,1-dichloroethane (DDD or TDE), Arch. Path. 48: 387, 1949. Google Scholar2. NicholsGardner JLI: Production of insulin sensitivity with the adrenocorticolytic drug DDD (2,2-bis(parachlorophenyl)-1, dichloroethane), J. Lab. and Clin. Med. 37: 229, 1951. MedlineGoogle Scholar3. NicholsGreen JHD: Effect of DDD therapy on metabolic response of dogs to ACTH injection, Am. J. Physiol. 176: 374, 1954. CrossrefMedlineGoogle Scholar4. SheehanSummersNichols HLVKJ: DDD therapy in Cushing's syndrome, Lancet 1: 312, 1953. CrossrefMedlineGoogle Scholar5. Tornblom N: Administration of DDD to diabetics with hyaline changes and hyperpolysaccharidemia, Acta med. scandinav. 154: 83, 1956. CrossrefMedlineGoogle Scholar6. ZimmermanBlockWilliamsHitchcockHoelocher BHWWLCRB: The effects of DDD (1,1-dichloro-2,2 bis (p-chlorophenyl) ethane) on the human adrenal: attempts to use an adrenal destructive agent in the treatment of disseminated mammary and prostatic cancer, Cancer 9: 940, 1956. CrossrefMedlineGoogle Scholar7. NicholsHennigar JGR: Studies on DDD, 2,2-bis (parachlorophenyl)-1,1-dichloroethane, Exper. Med. and Surg. 15: 310, 1957. MedlineGoogle Scholar8. CuetoBrown CJH: The chemical fractionation of an adrenocorticolytic drug, Endocrinology 62: 226, 1958. CrossrefGoogle Scholar9. CuetoBrown CJH: Biological studies on an adrenocorticolytic agent and the isolation of the active components, Endocrinology 62: 334, 1958. CrossrefMedlineGoogle Scholar10. BergenstalLipsettMoyHertz DMMBRR: Regression of adrenal cancer and suppression of adrenal function in man by o,p′DDD, Tr. A. Am. Physicians 72: 341, 1959. Google Scholar11. BergenstalLipsettMoyHertz DMMBRHR: Biological activities of steroids in relation to cancer, 1960, Academic Press, New York. Google Scholar12. WerbinOng HS: Improved colorimetric determination of urinary 17-ketosteroids, Anal. Chem. 26: 762, 1956. CrossrefGoogle Scholar13. SilberPorter RHCC: The determination of 17,21-dehydroxy-20-ketosteroids in urine and plasma, J. Biol. Chem. 210: 923, 1954. CrossrefMedlineGoogle Scholar14. BursteinLieberman SS: Hydrolysis of ketosteroid hydrogen sulfates by solvolysis procedures, J. Biol. Chem. 233: 331, 1958. CrossrefMedlineGoogle Scholar15. HertzBergenstalLubsJackson RDMHASJ: Observations on adrenal carcinoma with special reference to the effects of amphenone, Cancer 10: 765, 1957. CrossrefMedlineGoogle Scholar16. Moy RH: Unpublished data. Google Scholar17. VilarTullner OWW: Effects of o,p′DDD on histology and 17-hydroxycorticosteroids output of the dog adrenal cortex, Endocrinology 65: 80, 1959. CrossrefMedlineGoogle Scholar18. Tullner WW: Functional and structural recovery of the dog adrenal cortex after DDD treatment, Program of the Forty-second meeting of the Endocrine Society, Miami, 1960, p. 93. Google Scholar19. TullnerHertz WWR: Effect of intravenous o,p′DDD on plasma 17-hydroxycorticoid secretion in the dog, Endocrinology 66: 494, 1960. CrossrefGoogle Scholar20. Von Oettingen WF: The halogenated aliphatic, olefinic, cyclic, aromatic, and aliphaticaromatic hydrocarbons including the halogenated insecticides, their toxicity and potential changes, U. S. Government Printing Office, Washington, D. C., 1955, p. 347. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: DELBERT M. BERGENSTAL, M.D., F.A.C.P.; ROY HERTZ, M.D., F.A.C.P.; MORTIMER B. LIPSETT, M.D.; RICHARD H. MOY, M.D.Affiliations: Bethesda, Maryland*Received for publication June 21, 1960.Presented at the Forty-first Annual Session of The American College of Physicians, San Francisco, California, April 8, 1960.From the U. S. Public Health Service, National Cancer Institute, Endocrinology Branch, Bethesda, Maryland.†Deceased.‡Our material was obtained from the Edcan Chemical Company, Norwalk, Connecticut, and through the Cancer Chemotherapy National Service Center.Requests for reprints should be addressed to Mrs. Olga Collier, Building 10, Room 12-N-202, National Cancer Institute, Bethesda 14, Maryland. 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Epidemiology and treatment with mitotane and a review of the literatureAdrenocorticolytic DDT-metabolites: studies in mink, Mustela vison and otter, Lutra lutraENDOCRINE DISORDERS IN PREGNANCYPartial response after intensive chemotherapy for adrenal cortical carcinoma in a childPlasma level monitoring of mitotane (o,p'-DDD) and its metabolite (o,p'-DDE) during long-term treatment of cushing's disease with low dosesCovalent binding of o,p′-DDD in rabbit lung and isolated rabbit lung cellsClinical Features of Adrenocortical Carcinoma, Prognostic Factors, and the Effect of Mitotane TherapyEffect of o,p'-DDD on the in Vivo Incorporation of 3 H-Thymidine into DNA: Evidence for Induced Cell Proliferation in the Mouse LungChapter 14. Mechanism-Based Discovery of Anticancer AgentsCovalent Binding of Four DDD Isomers in the Mouse Lung: Lack of Structure SpecificityAdrenocortical CarcinomaAdrenocortical Carcinoma in ChildrenIn vitro macromolecular binding of 2-(2-chlorophenyl)-2-(4-chlorophenyl)-1,1-dichloroethane (o,p′-DDD) in the mouse lung and liverMetabolic activation and toxicity of a DDT-metabolite, 3-methylsulphonyl-DDE, in the adrenal Zona fasciculata in micePrimary aldosteronism by carcinoma of the adrenal cortexDiagnosis and Treatment of Functioning and Nonfunctioning Adrenocortical Neoplasms Including IncidentalomasRapid micromethod for the analysis of mitotane and its metabolite in plasma by gas chromatography with electron-capture detectionPrimary Hypogonadism Associated with O,P′ DDD (mitotane) Therapyo,p′-DDD in the mouse lung: Selective uptake, covalent binding and effect on drug metabolismComparison of adrenal cortical tumors in children and adultsAdrenal CortexTreatment of Adrenocortical Carcinoma: A Case Report and Review of the LiteratureAdrenal adenocarcinomas: Histologic grading and survivalThe regulation of adrenocortical function by control of growth and structurePrimary aldosteronism due to adrenal carcinomasRECOVERY OF ADRENAL FUNCTION AFTER TREATMENT OF ADRENOCORTICAL CARCINOMA WITH o,p’-DDDComplete response of metastasized adrenal cortical carcinoma with o,p'-ddd.Case report and literature reviewAdrenocortical tumorsAdrenocortical Carcinoma in ChildrenThe effect of o,p′-DDD on the adrenal cortex in sheepStimulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme a reductase activity by o,p′-DDDChemotherapy of Adrenal Cortical CarcinomaAdrenal adenocarcinomas: Diagnosis and managementBIBLIOGRAPHYMitotane (o, p′-DDD)Adrenal neoplasmsTreatment of Cushing's Disease by o,p′DDDo,p'—DDD and adrenal carcinomaChanges in corticosteroid synthesis of the human adrenal cortex in vitro, induced by treatment with o,p'-DDD for cushing's syndrome: evidence for the sites of action of the drugo,p′-DDD (mitotane) therapy of adrenal cortical carcinoma. Observations on drug dosage, toxicity, and steroid replacementDie NebennierenrindeExperience with adrenal cortical carcinomaNonfunctioning Tumors of the Adrenal GlandEstimation of o,p'-DDD in plasma by gas-liquid chromatographySteroid-Induced, Steroid-Producing, and Steroid-Responsive TumorsEffects of Pesticides and Related Compounds on Steroid Metabolism and Functiono,p'DDD Therapy in Invasive Adrenocortical CarcinomaDENIS BECKER, M.D., O. PETER SCHUMACHER, M.D., Ph.D., F.A.C.P.1-(o-Chlorophenyl)-1-(p-Chlorophenyl)-2,2-Dichloroethane (o,p’-DDD), an Adrenocorticolytic AgentThe Design of Organ-Imaging RadiopharmaceuticalsTreatment of an adrenal cortical carcinoma with a combination of o,p′-DDD and aminoglutethimideRegression of an adrenal cortical carcinoma and its neovascular bed following mitotane therapy: A case reportThe clinical and pathologic featurfs of “non-hormonal” adrenocortical tumors.Report of twenty new cases and review of the literatureChromatographic and biological aspects of DDT and its metabolitesCarcinoma of the adrenal gland in childrenEvaluation of Antineoplastic Activity: Requirements of Test SystemsSteroid Hormones and Breast CancerInsecticide Inhibition of 5α-Dihydrotestosterone Binding in the Rat Ventral ProstateEffects of dieldrin on 5α-dihydrotestosterone binding in the cytosol and nucleus of the rat ventral prostateChemotherapeutic management of the hormone-secreting endocrine malignanciesClinical therapeutics of adrenal disordersTreatment of Adrenocortical Carcinoma with o,p'-DDDMorphology of Chemical ImmunosuppressionDiagnostic and Therapeutic Problems in Spontaneous Cushing's Syndrome: A Review with Five Case ReportsResults of Treatment in 108 Patients with Cushing's SyndromeEffect of 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane on adrenocorticotropic hormone-induced steroidogenesis in various preparations in vitro of dog adrenal cortexVer�nderungen der Abbaugeschwindigkeit von Arzneimitteln und ihre Bedeutung f�r die PharmakotherapieThe Effects of Chlorinated Hydrocarbons on the Hepatic Monooxygenase SystemEndokrinologie in der KinderheilkundeREFERENCESAdrenalNeue ArzneimittelCushing’s Disease: Medical ManagementInhibitors of adrenal cortical functionTreatment of Cushing's DiseaseINFLUENCE OF CHLORINATED HYDROCARBONS AND ORGANOPHOSPHATE INSECTICIDES ON METABOLISM OF STEROIDSEFFECTS OF ORGANOCHLORINE INSECTICIDES ON BODY DEFENSE SYSTEMSCancer chemotherapyCUSHING'S SYNDROME IN A THREE MONTH OLD GIRLAdrenal Gland Adenocarcinoma: Report of Two CasesEffect of 2,2-bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane (o,p′-DDD) on cellular respiration in adrenal carcinomaGARDNER'S SYNDROME WITH ADRENAL CARCINOMASuppression of tumorous adrenal hyperfunction by aminoglutethimideCHEMICAL CONTROL OF HORMONE ACTION AND FERTILITYThe interaction of pesticides with other factorsEffects of some pesticides and related compounds on steroid function and metabolismEffects of Drugs on Neuroendocrine ProcessesSynthesis of 14C-Labeled Isomers of Dichlorodiphenyldichloroethanes(DDD)Adrenal cortical carcinomaAdrenal cortical carcinomaInhibitors of adrenal cortical functionAdrenocortical carcinomaDie Behandlung des Cushing-Syndroms mit o,p-DDD (2,2-bis (2-chlorophenyl-4-chlorophenyl)-1,1-dichloräthan)MODIFIERS OF ADRENOCORTICAL FUNCTION–SOME CLINICAL ASPECTSAdministration of Orto,para′‐DDD to Diabetics with Vascular Changes 1o,p′DDD in the treatment of advanced mammary carcinomaO-p′DDD therapy in Cushing's syndrome and in obesity with Cushingoid changesTumors and HormonesClinical and pathophysiologic aspects of adrenocortical carcinomaTreatment of Adrenocortical Cancer with O,P′-DDDANTONIO DA SILVA COELHO NETTO, M.D., BERNARDO LÉO WAJCHENBERG, M.D., CASSIO RAVAGLIA, M.D., VIRGILIO GONÇALVES PEREIRA, M.D., JOSÉ SHNAIDER, M.D., ARMANDO AGUIAR PUPO, M.D., ANTONIO BARROS DE ULHOA CINTRA, M.D., PH.D.Clinical and therapeutic observations in adrenal cancer: A report on 7 patients treated with o,p'-dddÜber den Einfluß von o,p-DDD [2,2-bis (2-chlorophenyl-4-chlorophenyl)-1,1-Dichloräthan] auf die Symptomatik und Steroidausscheidung bei Patienten mit abnormer adrenaler Steroidsekretion�ber den Einflu� von o,p-DDD [2,2-bis(2-chlorphenyl-4-chlorphenyl)-1,1-Dichlor�than] auf die Steroidausscheidung im Harn bei Nebennieren-Gesunden und bei einigen F�llen typischer adrenocorticaler Funktionsst�rungOUR NEW STERILISERSCHEMICAL ADRENALECTOMYMineralocorticoid action of adrenocortical hormonesCushing's Syndrome Due to Adrenocortical HyperplasiaEndocrine Pharmacology 1 October 1960Volume 53, Issue 4Page: 672-682KeywordsAdrenal cortexCancer chemotherapyChemotherapyDefined daily doseEndocrinologyInsecticideMedical servicesNauseaNecrosisOral administration ePublished: 1 December 2008 Issue Published: 1 October 1960 PDF downloadLoading ...