A Methylhydrazine Derivative in Hodgkin's Disease and Other Malignant Neoplasms

Abstract

Article1 July 1965A Methylhydrazine Derivative in Hodgkin's Disease and Other Malignant NeoplasmsTherapeutic and Toxic Effects Studied in 51 PatientsKURT W. BRUNNER, M.D., CHARLES W. YOUNG, M.D.KURT W. BRUNNER, M.D., CHARLES W. YOUNG, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-1-69 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMethylhydrazine derivatives form a new class of synthetic cytotoxic compounds. They possess antineoplastic activity in animal tumor systems (1, 2) and in patients with malignant lymphoma (3, 4). The most widely studied of these derivatives is N-isopropyl-alpha-(2-methylhydrazino)-ρ-toluamide hydrochloride, (Ro 4-6467, NSC-77213) (Figure 1).* It is reported to have teratogenic (5), immunosuppressive (6), and carcinogenic properties (7) in addition to antineoplastic activity.The molecular mechanism by which methylhydrazine derivatives produce biological effects is unknown. Observations in noncellular systems have disclosed that methylhydrazine is autoxidized in oxygen-containing aqueous solution with formation of hydrogen peroxide and oxygen-hydrogen radicals. These, in turn, degrade deoxyribonucleic...References1. BOLLAGGRUNBERG WE: Tumour inhibitory effects of a new class of cytotoxic agents: methylhydrazine derivatives. Experientia 19: 130, 1963. CrossrefMedlineGoogle Scholar2. BOLLAG W: The tumor-inhibitory effects of the methylhydrazine derivative RO 4-6467/1 (NSC-77213). Cancer Chemother. Rep. 33: 1, 1963. MedlineGoogle Scholar3. MARTZD'ALESSANDRIKEELBOLLAG GAHJW: Preliminary clinical results with a new antitumor agent RO 4-6467 (NSC-77213). Ibid., p. 5. Google Scholar4. MATHÉSCHWEISGUTHSCHNEIDERAMIELBERUMENBRULECATTANSCHWARZENBERG GOMJLLGAL: Methylhydrazine in the treatment of Hodgkin's disease. Lancet 2: 1077, 1963. CrossrefMedlineGoogle Scholar5. CHAUBEMURPHY SML: The teratogenic effects of 1-methyl-2-para (isopropylcarbamoyl) benzyl-hydrazine. HCl (MHl). Proc. Amer. Ass. Cancer Res. 5: 11, 1964. Google Scholar6. BOLLAG W: Suppression of the immunological reaction by methylhydrazines, a new class of antitumour agents. Experientia 19: 304, 1963. CrossrefMedlineGoogle Scholar7. KELLYO'GARAGADEKAYANCEYOLIVERIO MGRWKSTVT: Carcinogenic activity of a new antitumor agent, N-isopropyl-α-(2-methylhydrazino)-ρ-toluamide hydrochloride (NSC-77213). Cancer Chemother. Rep. 39: 77, 1964. MedlineGoogle Scholar8. BERNEISKOFLERBOLLAGKAISERLANGEMANN KMWAA: The degradation of deoxyribonucleic acid by new tumour inhibiting compounds: the intermediate formation of hydrogen peroxide. Experientia 19: 132, 1963. CrossrefMedlineGoogle Scholar9. WEITZELSCHNEIDERFRETZDORFF GFA: Cytostatischer Wirkungsmechanismus der methylhydrazine. Experientia 20: 38, 1964. CrossrefMedlineGoogle Scholar10. RUTISHAUSERBOLLAG AW: Cytological investigations with a new class of cytotoxic agents: methylhydrazine derivatives. Experientia 19: 131, 1963. CrossrefMedlineGoogle Scholar11. KARNOFSKY DA: Meaningful clinical classification of therapeutic responses to anti-cancer drugs. Clin. Pharmacol. Ther. 2: 709, 1961. CrossrefMedlineGoogle Scholar12. KARNOFSKYBURCHENAL DAJH: The clinical evaluation of chemotherapeutic agents in cancer, in Evaluation of Chemotherapeutic Agents, ed. by MACLEOD, C. M., Columbia University Press, New York, 1949, p. 191. Google Scholar13. PETERS MV: Study of survivals in Hodgkin 's disease treated radiologically. Amer. J. Roentgen. 63: 299, 1950. Google Scholar14. PETERSMIDDLEMISS MVKC: Study of Hodgkin's disease treated by irradiation. Amer. J. Roentgen. 79: 114, 1958. Google Scholar15. BEUTLERDERNALVING ERJAS: The hemolytic effect of primaquine VI. An in vitro test for sensitivity of erythrocytes to primaquine. J. Lab. Clin. Med. 45: 40, 1955. MedlineGoogle Scholar16. KARNOFSKY DA: Summary of results obtained with nitrogen mustard in the treatment of neoplastic disease. Ann. NY Acad. Sci. 68: 899, 1958. CrossrefMedlineGoogle Scholar17. MILLERDIAMONDCRAVER DGHDLF: The clinical use of chlorambucil. New Eng. J. Med. 261: 525, 1959. CrossrefMedlineGoogle Scholar18. DOANWISEMANBOURONCLE CABKBA: Clinical evaluation of CB 1348 in leukemias and lymphomas. Ann. NY Acad. Sci. 68: 979, 1958. CrossrefMedlineGoogle Scholar19. ARMSTRONGDYKEFOUTSGAHIMER JGRWPJJE: Hodgkin's disease, carcinoma of the breast, and other tumors treated with vinblastine sulfate. Cancer Chemother. Rep. 18: 49, 1962. MedlineGoogle Scholar20. BOHANNONMILLERDIAMOND RADGHD: Vincristine in the treatment of lymphomas and leukemias. Cancer Res. 23: 613, 1963. MedlineGoogle Scholar21. WRIGHTHURLEYKORSTMONTOROHNWILLLOUIS TLJDRRWRJJJJ: Vinblastine in neoplastic disease. Ibid., p. 169. Google Scholar22. FROSTGOLDWEINBRYAN JWMIJA: Clinical experience with vincaleukoblastine in far-advanced Hodgkin's disease and various malignant states. Ann. Intern. Med. 56: 854, 1962. LinkGoogle Scholar23. RUSSELLRUSSELL LBWL: An analysis of the changing radiation response of the developing mouse embryo. J. Cell Comp. Physiol. 43: Supp. 1, 103, 1954. CrossrefGoogle Scholar24. LEWIS EB: Leukemia and ionizing radiation. Science 125: 965, 1957. CrossrefMedlineGoogle Scholar25. MURPHYDEL MOROLACON MLAC: The comparative effects of five polyfunctional alkylating agents on the rat fetus with additional notes on the chick embryo. Ann. NY Acad. Sci. 68: 762, 1958. CrossrefMedlineGoogle Scholar26. WALPOLE AL: Carcinogenic action of alkylating agents. Ibid., p. 750. Google Scholar27. COHLANDANCISKITAY SQJD: Letter to the Editor. Lancet 1: 1390, 1964. CrossrefMedlineGoogle Scholar28. FERM VH: Congenital malformations in hamster embryos after treatment with vinblastine and vincristine. Science 141: 426, 1963. CrossrefMedlineGoogle Scholar29. ARMSTRONGDUKEFOUTSJANSEN JGRWPJCJ: Delivery of a normal infant during the course of oral vinblastine sulfate therapy for Hodgkin's disease. Ann. Intern. Med. 61: 106, 1964. LinkGoogle Scholar30. ROSENZWEIGCREWS AIQE HOPWOOD H. G. : Vinblastine sulfate in Hodgkin's disease in pregnancy. Ibid., p. 108. Google Scholar31. LACHER MJ: Use of vinblastine sulfate to treat Hodgkin's disease during pregnancy. Ibid., p. 113. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New YorkFrom the Medical Oncology Service, Department of Medicine, Memorial Hospital and James Ewing Hospital, and Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N. Y.This research was supported in part by grants CA-03215 and CA-5826 from the National Cancer Institute, U. S. Public Health Service, Bethesda, Md.Requests for reprints should be addressed to Charles W. Young, M.D., Sloan-Kettering Institute, 410 East 68th St., New York, N. Y. 10021 .*At present this is the only methylhydrazine derivative that has been extensively studied in patients; accordingly, we use the term methylhydrazine throughout this report to refer to Ro 4-6467 (NSC-77213). PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNeurologic ComplicationsChemotherapeutic drugs that penetrate the blood–brain barrier affect the development of hyperactive delirium in cancer patientsNeurologic ComplicationsNeurological complications of chemotherapy to the peripheral nervous systemAssessment of the Evolution of Cancer Treatment TherapiesNeurologic ComplicationsReappraisal of the use of procarbazine in the treatment of lymphomas and brain tumorsThe emerging role of reactive oxygen species in cancer therapyCommentary on and reprint of DeVita VT Jr, Serpick AA, Carbone PP, Combination chemotherapy in the treatment of advanced Hodgkin's disease, in Annals of Internal Medicine (1970) 73:881–895Review : Infertility after chemotherapy: A review of the risks and strategies for preventionTesticular germ cell populations in the adult rat after continuous in-vivo testicular infusion of inhibin-A and activin-APeripheral NeuropathyHypersensitivity reactions from antineoplastic agentsSystemische Chemotherapie maligner MelanomeCancer in the ElderlyRegioselective synthesis of unsymmetrical deuterium labelled hydrazines and azoxy compoundsMetabolic activation of procarbazineThe chemosensitivity of a new experimental model—the M5076 reticulum cell sarcomaThe Chemotherapy of Human Malignant MelanomaImmediate and Delayed Neurotoxicity After Mechlorethamine Preparation for Bone Marrow TransplantationKEITH M. SULLIVAN, M.D., RAINER STORB, M.D., HOWARD M. SHULMAN, M.D., CHENG-MEI SHAW, M.D., ALEXANDER SPENCE, M.D., CASSANDRA BECKHAM, B.S., REGINALD A. CLIFT, F.I.M.L.S., C. DEAN BUCKNER, M.D., PATRICIA STEWART, M.D., E. DONNALL THOMAS, M.D.Klinik der malignen LymphomeTeratogenicity induced in cultured rat embryos by the serum of procarbazine treated ratsThe Effects of Antineoplastic Therapy on Growth and Development in ChildrenHypersensitivity Reactions to Cancer Chemotherapeutic AgentsRAYMOND B. WEISS, M.D., SALVADOR BRUNO, M.D.Procarbazine-Induced Skin Reactions in Hodgkin's Disease and Other Malignant LymphomasNeuropsychiatric effects of chemotherapeutic agents for cancerThe chemotherapy of Hodgkin's disease.Past experiences and future directionsMucocutaneous side effects of cancer chemotherapyMetabolic activation of procarbazineMutagenicity, carcinogenicity and teratogenicity of procarbazineHydrazines and TriazenesToxicity of Chemotherapeutic AgentsChemotherapy of the Non-Hodgkin's LymphomasFrom wild fowl to stalking horses: Alchemy in chemotherapy.Fifth annual David A. Karnofsky memorial lectureProcarbazineDrugs Five Years Later ProcarbazineSAMUEL D. SPIVACK, M.D.Integration of chemotherapy into combined modality therapy of solid tumorsChemotherapy of non-Hodgkin's lymphomasNeurotoxicity of Commonly Used Antineoplastic AgentsDie LymphogranulomatoseSingle Agent Sequential Chemotherapy in Non-Hodgkin's LymphomasChemotherapy of malignant melanomaHodgkin's disease and non-Hodgkin's lymphoma—The surgeon's role in therapyPotential environmental chemical hazards part I: DrugsThe Present Status of Chemotherapy in DermatologyCombination sequential chemotherapy in advanced reticulum cell sarcomaHypersensitivity to procarbazine (Matulane®) manifested by fever and pleuropulmonary reactionThe immunosuppressive activity of procarbazine hydrochloride in canine renal allografts by donor pretreatmentThe Present Status of Cancer ChemotherapyCyclic chemotherapy in lymphomaChemotherapy of the LymphomasPresent Position of Radical and Palliative Treatment of Malignant LymphomasCombination Chemotherapy in the Treatment of Advanced Hodgkin's DiseaseVINCENT T. DEVITA JR., M.D., F.A.C.P., ARTHUR A. SERPICK, M.D., F.A.C.P., PAUL P. CARBONE, M.D.clinical experience with procarbazine in Hodgkin's disease, reticulum cell sarcoma, and lymphosarcomaLangzeitbehandlung der fortgeschrittenen vinblastinresistenten Lymphogranulomatose mit Ibenzmethyzin (NatulansR)Combination chemotherapy with nitrogen mustard, vincristine, procarbazine, and prednisone in lymphosarcoma and reticulum cell sarcomaTolerance to Chemotherapy After Prior Irradiation for Hodgkin's DiseaseROBERT E. CURRAN, M.D., RALPH E. JOHNSON, M.D.ProcarbazineProcarbazine hydrochloride in childhood cancerComparative effects of vinblastine and procarbazine in advanced Hodgkin's diseaseFetal malformations produced in rats byN-isopropyl-α-(2-methylhydrazino)-p-toluamide hydrochloride (procarbazine)Clinical Management of Hodgkin's DiseaseTreatment of some chronic hemoblastoses with a derivative of Methylhydrazine (Natulan)Clinical trials with N-isopropyl-α-(2-methylhydrazino)-p-toluamide hydrochloride in malignant lymphoma and other disseminated neoplasiaRecent Advances in the Treatment of Malignant HemopathiesPHARMACOLOGY OF CANCER CHEMOTHERAPYMISCELLANEOUS AGENTS AND TECHNIQUESChemical Suppression of Adaptive ImmunityThe Treatment of Hodgkin's DiseaseHodgkin's DiseaseSelection of Anticancer Drugs for Inclusion in Memorial Hospital FormularyChemotherapy of Hodgkin's diseaseClinical Staging and Treatment of Lymphosarcoma and Reticulum Cell Sarcoma. 1 July 1965Volume 63, Issue 1Page: 69-86KeywordsCancer chemotherapyHematology and oncologyHospital medicineImmunosuppressivesLymphomaMedical servicesNauseaOral administrationPatientsSarcoma Issue Published: 1 July 1965 PDF DownloadLoading ...