Cancer Chemotherapy National Service Center Research Articles

Critical Considerations in Anticancer Drug Development and Dosing Strategies: The Past, Present, and Future.

Critical Considerations in Anticancer Drug Development and Dosing Strategies: The Past, Present, and Future.

Historical aspects of antitumor compounds from plants, including homoharringtonine (Omacetaxine Mepesuccinate, SynriboTM)

Various preparations derived from vascular plants have been used utilized to treat tumors or cancerous conditions for centuries. The available literature was summarized by Jonathan Hartwell in a remarkable series of papers “Plants Used Against Cancer” published in Lloydia from 1967 to 1971. The U.S. National Cancer Institute (NCI) established the Cancer Chemotherapy National Service Center (CCNSC) in 1955. Hartwell transferred to CCNSC in 1957, and under his guidance a major program to discover plant anticancer constituents was developed. Arrangements were made between the NCI and the U.S. Department of Agriculture (USDA) for extensive plant collections in 1960. Many of the collections were from countries that were involved in the Food for Peace Program, Public Law (PL) 480. The Wisconsin Alumni Research Foundation (WARF) was awarded an extraction and screening contract, and research contracts were awarded to Drs. Monroe Wall, Morris Kupchan, Norman Farnsworth, John Cassady and others. When plant seeds were obtained, they were sent to the Northern Regional Research Laboratory (NRRL) in Peoria, Illinois, where they were examined in a program to identify potential new crops. Extracts of many of the seeds were prepared and screened for antitumor activity and the more significant results obtained from the seed extracts will be summarized.

A History of Cancer Chemotherapy

The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

Historical and methodological developments in clinical trials at the national cancer institute

The first randomized clinical trial at the National Cancer Institute (NCI), planned in 1954, commenced in 1955 for the treatment of patients with acute leukaemia. The programme in clinical trials at NCI had strong influence from the clinician and administrator, C. Gordon Zubrod, who introduced the randomized clinical trial at NCI and organized the co-operative clinical trials programme of the Cancer Chemotherapy National Service Center (CCNSC) beginning about 1955. The biostatistician, Marvin Schneiderman, collaborated on the first randomized trials in acute leukaemia and solid tumours and recruited the biostatisticians and statistical centres in the early phase of the co-operative clinical trials programme of the CCNSC. From the beginning, there was acceptance of the principles of the randomization of patients and the statistical analysis of data. The sequence of clinical trials for a new agent included the non-randomized phase I (dosage finding) and phase II (preliminary efficacy) trials as well as the phase III (comparison of treatments) trials. New concepts for the treatment of patients developed from 1955 to the mid-1960s included the combination of therapies with independent activity to increase response rates and the administration of therapy to patients in a disease-free (remission) state to prolong the disease-free state. Methodological developments related to clinical trials up to the mid-1960s included: a plan for phase II trials (Gehan); a generalization of the Wilcoxon test for the comparison of survival distributions with right-censored data (Gehan); a test of proportional hazards for survival distributions, which later became known as the Mantel-Haenszel test (Mantel), and an exponential regression model with an explanatory variable (Feigl and Zelen).

Adventures in Organic Sulfur Chemistry

Abstract On several occasions, SULFUR REPORTS has invited persons who have done outstanding work in sulfur chemistry to summarize highlights of their research career in a semiautobiographical review. The present account is from a distinguished chemist who has contributed importantly for nearly 50 years to medicinal and organic aspects of sulfur chemistry. Ernest E. Campaigne (who prefers simply E. Campaigne) was born in Chicago, Illinois, in 1914. He received the B.S. and M.S. degrees in chemistry and the Ph.D. degree in biochemistry at Northwestern University. After a short stretch of teaching at Bowdoin College, he spent a postdoctoral year with the well-known sulfur chemist C.M. Suter in the Department of Chemistry at Northwestern University and a year in research at the M.D. Anderson Hospital for Cancer Research in Texas. In 1943, he joined the faculty of Indiana University, where he rose to the rank of Professor of Chemistry in 1953 and from which he became Professor Emeritus in 1979. Over the years he has spent time at the Oak Ridge National Laboratory, the Universities of California at Los Angeles and San Francisco, University College (London), Cambridge University, and many of the universities in Australia. He has been a consultant for many years to major industrial companies, as well as to the National Institutes of Health, the Office of the Surgeon General of the U.S. Army, and the Cancer Chemotherapy National Service Center. For the American Chemical Society, Professor Campaigne not only has had many important general responsibilities but has served in many ways in the Divisions of Medicinal and Organic Chemistry; he also has played a role in the affairs of IUPAC. He has served on several editorial boards, has his name on four textbooks, and has authored nearly 300 publications in medicinal and organic chemistry, particularly in relevance to sulfur chemistry and heterocycles. The table of contents below shows the breadth of his interests and the areas highlighted in his article. Included are interesting ideas others may wish to carry forward.

Structural modifications of the vinca alkaloids

The vinca alkaloids were discovered independently in two separate laboratories by a combinat ion of serendipity and what we have called rational broad spectrum tumor screening. In the first case, R. L. Noble and his colleagues in the Collip Labora tory at the University of Western Ontar io were examining extracts ofCatharanthus roseus G. Don ( Vinca rosea Linn.) for their effects on blood glucose because of unconfirmed reports in various parts of the world that the plant was being used for the treatment of diabetes. These investigators (4) found by chance observation that the extracts produced profound leukopenia in the rat, and they isolated an alkaloid which demonstrated such activity as a crystalline sulfate, which they named vincaleukoblastine (VLB). They speculated that it might have potential chemotherapeutic properties. This is the drug which is currently marketed as Velban ~'~ (vinblastine sulfate, Lilly). Unknown to the Canadian group, a group of investigators in the Lilly Research Laboratories had observed profound activity in extracts from the same plant against the P-1534 lymphocytic leukemia in DBA/2 mice and had isolated a second alkaloid with antileukemic activity which they named leurosine (3). We were also able to show that after VLB and leurosine were removed from the extracts that there were components remaining with profound ant i tumor activity. These were eventually identified as leurocristine (Oncovin, vincristine sulphate, Lilly) and leurosidine (12). The discovery in the Lilly Research Laboratories resulted from a privately funded ant i tumor screening program mounted in response to a national effort to increase the detection and development of new anticancer drugs through what was then the Cancer Chemotherapy National Service Center (CCNSC). We had long felt that harnessing the major pharmaceutical laboratories to a single set of tests or test systems would have been an error. It had been the experience of most such laboratories that, as new systems, tests, techniques, etc., are devised, a new class of agent was frequently found. The more varied the system in use, the greater the probability of different kinds of materials being detected. In the nationally organized program, the screening philosophy appeared to be based upon the concept of using as few detection systems as possible that would detect the largest number of drugs currently considered as having clinical activity. This was clearly an at tempt at a cost-effective approach. Our concern was that cancer was a heterogenous family of proliferative diseases, and that just as cancer drugs had tumor spectra, experimental neoplasms also had drug spectra. I f this were true, continuous use of a few or even single murine neoplasms for cancer screening might not be expected to detect new or novel drugs, much less predict for activity against a broad spectrum of neoplasms and histological types. While performing well in terms of detecting novel structures, our system did not predict

Tumor-Inhibitory Agent from Hyptis emoryi (Labiatae)

The extract of Hyptis emoryi (Labiatae) has shown tumor-inhibiting properties in the 5WA16 test system of the Cancer Chemotherapy National Service Center. By means of melting point, mixed melting point, IR, mass spectrometry, elemental analysis, and preparation of derivatives, the agent responsible for this action was shown to be betulinic acid.

Transplantation of allogeneic tumors in rats and mice treated with azathioprine, prednisone and antilymphocyte serum.

SummaryIn a study of the effects of anti-lymphocytic serum (ALS), azathioprine, and prednisone on the acceptance-rates of three mouse and two rat tumors in allogeneic hosts, marked increases in average tumor acceptance rates, and usually but not always in terminal tumor weights, were observed following treatment with ALS alone, or in combination with either or both or the other two agents. The technique of allogeneic tumor grafts offers a simple semiquantitative procedure to evaluate the effect of drugs, sera, and related agents on the immunocompetence of animal systems, especially in relation to control mechanisms of tumor induction and development.We thank Dr. Arthur E. Bogden, Mason Research Institute, for the prostatic carcinoma 11095 and mammary adenocarcinoma 1/C; Dr. Harry B. Wood, Cancer Chemotherapy National Service Center, National Cancer Institute, for supplying azathioprine and prednisone; and Mr. Charles Kelley and Mr. Donald Dykes for their technical assistance.

Dihydrofolate Reductases: Structural and Mechanistic Aspects

Annals of the New York Academy of SciencesVolume 186, Issue 1 p. 85-99 Dihydrofolate Reductases: Structural and Mechanistic Aspects* F. M. Huennekens Ph.D., F. M. Huennekens Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037Search for more papers by this authorR. B. Dunlap Ph.D., R. B. Dunlap Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 U.S. Public Health Service Research Fellow. Present address: Department of Chemistry, University of South Caroline, Columbia, S. C.Search for more papers by this authorJ. H. Freisheim Ph.D., J. H. Freisheim Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 Postdoctoral Fellow of the American Cancer Society. Present address: Department of Biological Chemistry, University of Cincinnati College of Medicine, Cincinnati, Ohio.Search for more papers by this authorL. E. Gundersen Ph.D., L. E. Gundersen Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037Search for more papers by this authorN. G. L. Harding M.D., Ph.D., N. G. L. Harding M.D., Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 Fellow of the Medical Research Council of England (1969); Dernham Junior Fellow in Oncology (1970). Present address: The Postgraduate Medical School, Hills Road, Cambridge, England.Search for more papers by this authorS. A. Levison Ph.D., S. A. Levison Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 U.S. Public Health Service Special Research Fellow.Search for more papers by this authorG. P. Mell Ph.D., G. P. Mell Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 Department of Chemistry, University of Montana, Missoula, Mont.Search for more papers by this author F. M. Huennekens Ph.D., F. M. Huennekens Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037Search for more papers by this authorR. B. Dunlap Ph.D., R. B. Dunlap Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 U.S. Public Health Service Research Fellow. Present address: Department of Chemistry, University of South Caroline, Columbia, S. C.Search for more papers by this authorJ. H. Freisheim Ph.D., J. H. Freisheim Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 Postdoctoral Fellow of the American Cancer Society. Present address: Department of Biological Chemistry, University of Cincinnati College of Medicine, Cincinnati, Ohio.Search for more papers by this authorL. E. Gundersen Ph.D., L. E. Gundersen Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037Search for more papers by this authorN. G. L. Harding M.D., Ph.D., N. G. L. Harding M.D., Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 Fellow of the Medical Research Council of England (1969); Dernham Junior Fellow in Oncology (1970). Present address: The Postgraduate Medical School, Hills Road, Cambridge, England.Search for more papers by this authorS. A. Levison Ph.D., S. A. Levison Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 U.S. Public Health Service Special Research Fellow.Search for more papers by this authorG. P. Mell Ph.D., G. P. Mell Ph.D. Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, Calif. 92037 Department of Chemistry, University of Montana, Missoula, Mont.Search for more papers by this author First published: November 1971 https://doi.org/10.1111/j.1749-6632.1971.tb46958.xCitations: 53 * This work was supported by grants from the American Cancer Society (P-302) and the National Cancer Institute, National Institutes of Health (CA 6522), and by a contract (PH 43–65–14) with the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume186, Issue1Folate Antagonists as Chemotherapeutic AgentsNovember 1971Pages 85-99 RelatedInformation

Processing plant samples with a compost mill to hasten drying and reduce bulk

Introduction Agricultural Research Service botanists have supplied more than 17,000 plant samples for anti-tumor screening by the Cancer Chemotherapy National Service Center of the National Cancer Institute. Annual procurement has ranged up to 2,200 1to 2-lb samples for initial screening, and up to 200 large samples of biologically active plant materials for chemical fractionation to isolate, characterize, and evaluate anti-tumor constituents. During the early years of this program, field projects were concentrated largely in the United States and Mexico. More recently, procurement increasingly has been concentrated abroad. As procurement turned overseas, the expense of shipping bulky collections has become a much more significant item in project costs. While domestic shipping costs (either via surface or air freight) are based on weight of the material shipped, shipping costs from foreign ports are based on volume and can range up to $2.50 per cu ft. The latter require expensive crating, the cost of which is also based on volume. As our attention turned to overseas procurement, it became evident that equipment to chop bulky plant material would be highly desirable, because chopping would greatly reduce volume and permit more efficient packing. Such equipment should be driven by its own source of power, preferably a gasoline engine. It should be durable, compact, fairly light in weight, and highly portable for day to day use in the field. It should chop most plant materials into small pieces so that the broad range of samples to be collected would occupy a minimum of space. A compost mill2 filled these requirements completely.

Effects of some antitumor agents on growth and glycolytic enzymes of the flagellate Crithidia.

Some antitumor agents known to specifically inhibit certain tumor cell enzymes were examined for activity against glycolytic enzymes and growth of the insect trypanosomatid, Crithidia fasciculata. The cytoplasmic enzymes hexokinase, alpha-glycerophosphate dehydrogenase, malic dehydrogenase, and glucose-6-phosphate dehydrogenase were tested. Agaricic acid (2-hydroxy-1,2,3-nonadecane tricarboxylic acid) was highly inhibitory (50 to 100%) to malic and alpha-glycerophosphate dehydrogenases at approximately 3 x 10(-5)m; 2-(p-hydroxyphenyl)-2-phenylpropane (2 x 10(-4)m), and 5,6-dichloro-2-benzoxazolinone (5 x 10(-4)m) were less effective (50% inhibition) against them. The antiprotozoal agents primaquine (4 x 10(-4)m) and Melarsoprol (8 x 10(-4)m) were 30 to 40% inhibitory. Agaricic acid, 2-(p-hydroxyphenyl)-2-phenylpropane, and 5,6-dichloro-2-benzoxazolinone inhibited growth of Crithidia at less than 10(-4)m. Eight other test compounds from the Cancer Chemotherapy National Service Center (CCNSC) were not toxic to cell growth, although two (4-biphenylcarboxylic acid and 1-[p-chlorobenzyl]-2-ethyl-5-methyl-indole-3-acetic acid) inhibited Crithidia alpha-glycerophosphate dehydrogenase below 1 mm. All of the compounds used specifically inhibited cancer cell alpha-glycerophosphate dehydrogenase. The corresponding enzyme in pathogenic African trypanosomes is important in their terminal respiration. C. fasciculata may be useful in preliminary evaluation of chemotherapeutic agents as potential trypanocides.

Antitumor Agents from Bursera microphylla (Burseraceae) II: Isolation of a New Lignan—Burseran

Bursera microphylla (Burseraceae) A. Gray has yielded a second component which has demonstrated activity in the cell culture test system of the Cancer Chemotherapy National Service Center (CCNSC). On the basis of NMR, mass, and IR spectrometry, the structure of a new lignan, 3-(3,4-methylenedioxybenzyl)-4-(3“,4”,5-trimethoxybenzyl) tetrahydrofuran (named burseran), is proposed.

Studies in cyclocopolymerization. IV. Evidence of charge‐transfer complexes as intermediates in cyclocopolymerization of 1,4‐dienes with alkenes

AbstractCharge‐transfer complexes in solutions of comonomers such as divinyl ether and maleic anhydride have been identified by use of ultraviolet spectroscopy. Equilibrium constants and molar extinction coefficients were determined for several of these complexes. It appears reasonable that the cyclic units formed in these copolymers result from free‐radical initiation of the charge‐transfer complex, which preorients the comonomers into a conformation favorable for formation of copolymer in the observed comonomer ratio of 1:2. Copolymers prepared and studied were those of divinyl ether with N‐substituted maleimides having the following substituents on nitrogen: (a) hydrogen, (b) methyl, (c) ethyl, (d) n‐propyl, (e) isopropyl (f) n‐butyl, (g) isobutyl, (h) benzyl, (i) α‐naphthyl, (j) phenyl, (k) p‐methoxyphenyl. These copolymers were characterized by elemental analyses to establish the comonomer ratios and by viscosity measurements and in certain instances by determination of molecular weights by the vapor‐pressure osmometry method. The copolymer of divinyl ether and maleic anhydride has been found to be an effective antitumor agent by the Cancer Chemotherapy National Service Center, National Institutes of Health. Consequently, these copolymers were also submitted for evaluation in this program, and several have been found to possess favorable inhibiting action on tumor growth.

Inhibition of nucleic acid and protein synthesis in Escherichia coli by a new triazenomidazole.

Methyl S (or 4) - (3,3 - dimethyl −1 - triazeno) imidazole-4 (or 5)-carboxylate(1), designated NSC 87982 by the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, has been reported to be a potent inhibitor of Gram-positive and Gram-negative bacteria, yeasts, filamentous fungi and algae in vitro and to protect mice against an experimental infection of Staphylococcus aureus (2). Microbiological assay of various mouse tissues indicates that not only are significantly high blood levels obtained following oral, intraperitoneal, or intravenous administration of the drug, but also that detectable concentrations of NSC 87982 are found in the brain and other organs of the mice(3). The broad-spectrum antimicrobial activity of NSC 87982 and the knowledge that it is being considered for clinical trial prompted a study of the mechanism of action of this compound.Materials and methods. The inhibitory activity of NSC 87982 against numerous strains of Escherichia coli a...

Phytochemical Investigation of Abies Concolor

Extracts of the bark of Abies concolor have shown antitumor activity against the adenocarcinoma of the duodenum test system of the Cancer Chemotherapy National Service Center. One of the active materials appears to be a complex tannin. The isolation of the active fractions has been reported utilizing solvent extraction, column, paper, and thin-layer chromatography.

A convenient synthesis of 6‐aza‐2′‐deoxycytidine

Journal of Heterocyclic ChemistryVolume 3, Issue 2 p. 226-227 Note A convenient synthesis of 6-aza-2′-deoxycytidine† George L. Tong, George L. Tong Life Sciences Research, Stanford Research Institute, Menlo Park, California 94025Search for more papers by this authorWilliam W. Lee, William W. Lee Life Sciences Research, Stanford Research Institute, Menlo Park, California 94025Search for more papers by this authorLeon Goodman, Leon Goodman Life Sciences Research, Stanford Research Institute, Menlo Park, California 94025Search for more papers by this author George L. Tong, George L. Tong Life Sciences Research, Stanford Research Institute, Menlo Park, California 94025Search for more papers by this authorWilliam W. Lee, William W. Lee Life Sciences Research, Stanford Research Institute, Menlo Park, California 94025Search for more papers by this authorLeon Goodman, Leon Goodman Life Sciences Research, Stanford Research Institute, Menlo Park, California 94025Search for more papers by this author First published: June 1966 https://doi.org/10.1002/jhet.5570030226Citations: 8 † This work is carried out under the auspices of the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, U. S. Public Health Service, Contract No. PH 43-64-500. The opinions expressed are those of the authors and not necessarily those of the Cancer Chemotherapy National Service Center AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume3, Issue2June 1966Pages 226-227 RelatedInformation

Present Status of Surgical Adjuvant Lung-Cancer Chemotherapy

ABSTRACT The concept, methods, materials, and present findings of the Veteran's Administration Surgical Adjuvant Lung-Cancer Chemotherapy Study Group are summarized. There is no indication that mechlorethamine (Mustargen) hydrochloride as used by the group has a beneficial effect on survival. The effect of cyclophosphamide (Cytoxan) therapy has been observed only briefly. Curative pulmonary resection offers hope of cure to 30% of patients surviving operation.Surgical resection of cancer apparently limited to the lung has long offered the main chance of cure, but this has been true for only about 30% of carefully selected cases. Experimental evidence that small tumor implants could be prevented by chemotherapy created hope of a beneficial effect in patients.17The Cancer Chemotherapy National Service Center of the National Cancer Institute18 in 1957 started a program of research to develop and screen tumoricidal compounds for use on patients. Mechlorethamine was being used clinically and was selected by

Isolation of a Potential Antitumor Fraction from Rumex hymenosepalus

Extracts of <i>Rumex hymenosepalus</i> have shown antitumor activity against the Sarcoma 180 and Walker 256 test systems of the Cancer Chemotherapy National Service Center, Bethesda, Md. The extracts have been fractionated by means of solvent extraction and paper chromatography into two distinct fractions. The partial characterization of these fractions is described, including the characterization of leucocyanidin as one of the constituents and the identification of benzoic acid as a hydrolysis product of a polyphenolic ester.

Biochemical studies on the antiviral activities of the isatin-beta-thiosemicarbazones.

Annals of the New York Academy of SciencesVolume 130, Issue 1 p. 80-91 BIOCHEMICAL STUDIES ON THE ANTIVIRAL ACTIVITIES OF THE ISATIN-β-THIOSEMICARBAZONES* W. E. Magee, W. E. Magee Virology and Biochemistry Research, The Upjohn Company, Kalamazoo. Mich.Search for more papers by this authorM. K. Bach, M. K. Bach Virology and Biochemistry Research, The Upjohn Company, Kalamazoo. Mich.Search for more papers by this author W. E. Magee, W. E. Magee Virology and Biochemistry Research, The Upjohn Company, Kalamazoo. Mich.Search for more papers by this authorM. K. Bach, M. K. Bach Virology and Biochemistry Research, The Upjohn Company, Kalamazoo. Mich.Search for more papers by this author First published: July 1965 https://doi.org/10.1111/j.1749-6632.1965.tb12542.xCitations: 15 * This work was supported, in part, by contract No. PH43-63-556, of the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume130, Issue1Antiviral SubstancesJuly 1965Pages 80-91 RelatedInformation

THERAPEUTIC CASTRATION IN THE TREATMENT OF ADVANCED BREAST CANCER.

CancerVolume 17, Issue 9 p. 1197-1202 ArticleFree Access Therapeutic castration in the treatment of advanced breast cancer B. J. Kennedy M.D., B. J. Kennedy M.D. Department of Internat Medicine, University of Minnesota Medical Center, Minneapolis, Minn. 55455Search for more papers by this authorIgnacio E. Fortuny M.D., Ignacio E. Fortuny M.D. Department of Internat Medicine, University of Minnesota Medical Center, Minneapolis, Minn. 55455Search for more papers by this author B. J. Kennedy M.D., B. J. Kennedy M.D. Department of Internat Medicine, University of Minnesota Medical Center, Minneapolis, Minn. 55455Search for more papers by this authorIgnacio E. Fortuny M.D., Ignacio E. Fortuny M.D. Department of Internat Medicine, University of Minnesota Medical Center, Minneapolis, Minn. 55455Search for more papers by this author First published: September 1964 https://doi.org/10.1002/1097-0142(196409)17:9<1197::AID-CNCR2820170916>3.0.CO;2-TCitations: 36AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Beatson, G. T.: On treatment of inoperable cases of carcinoma of mamma; suggestions for new method of treatment with illustrative cases. Lancet 2: 104– 107, 1896. 2 Block, G. E.; Lampe, I.; Vial, A. B., and Coller, F. A.: Therapeutic castration for advanced mammary cancer. Surgery 47: 877– 884, 1960. 3 Boyd, S.: On oöphorectomy in cancer of breast. Brit. M. J. 2: 1161– 1167, 1900. 4 De Courmelles, F.: La radiothérapie combinée du sein et des ovaires contre les tumeurs du sein. Compt. rend. Acad. sc. 174: 503, 1922. 5 Daniel, O.: Control of disseminated breast cancer. Proc. Roy. Soc. Med. 54: 555– 557, 1961. 6 Douglas, M.: Treatment of advanced breast cancer by hormone therapy. Brit. J. Cancer 6: 32– 45, 1952. 7 Dresser, R.: Effect of ovarian irradiation on bone metastases of cancer of breast. Am. J. Roentgenol. 35: 384– 391, 1936. 8 Gordon, D. L., and Segaloff, A.: Castration as palliative therapy for advanced breast cancer. In A. Segaloff, Ed.: Breast Cancer; The Second Biennial Louisiana Cancer Conference. St. Louis, Mo. The C. V. Mosby Company. 1958; pp. 187– 198. 9 Halberstaedter, L., and Hochman, A.: Artificial menopause and cancer of breast. J. A. M. A. 131: 810– 816, 1946. 10 Hall, T. C.; Dederick, M. M.; Nevinny, H. B., and Muench, H.: Prognostic value of response of patients with breast cancer to therapeutic castration. In Cancer Chemotherapy Reports, No. 31. Bethesda, Md. Cancer Chemotherapy National Service Center. 1963; pp. 47– 48. 11 Jacobson, J. E.: Wilcoxon two-sample statistic; tables and bibliography. J. Am. Statist. A. 58: 1086– 1103, 1963. 12 Kennedy, B. J.: Present status of hormone therapy in advanced breast cancer. Radiology 69: 330– 340, 1957. 13 Kennedy, B. J.; Mielke, P. W., Jr., and Fortuny, I. E.: Therapeutic castration versus prophylactic castration in breast cancer. Surg. Gynec. & Obst. 118: 524– 540, 1964. 14 Lett, H.: In Analysis of 99 cases of inoperable carcinoma of breast treated by oöphorectomy. In Royal Medical and Chirurgical Society. Lancet 1: 227– 228, 1905. 15 Lewison, E. F.: Prophylactic versus therapeutic castration in total treatment of breast cancer; collective review. Obst. & Gynec. Surv. 17: 769– 802, 1962. 16 Macdonald, I.: Endocrine ablation in disseminated mammary carcinoma. Surg. Gynec. & Obst. 115: 215– 222, 1962. 17 Mininni, D., and Sbaragli, F.: L'ovariectomia nel cancro della mamella. Osped. d'ital. chir. 4: 450– 469, 1961. Cited by Lewison, E. F.15 18 Pearson, O. H.; West, C. D.; Li, M. C.; Maclean, J. P., and Treves, N.: Endocrine therapy of metastatic breast cancer. A. M. A. Arch. Int. Med. 95: 357– 364, 1955. 19 Schinzinger: Über Carcinoma mammae. [Abstr.] Zentralbl. Chir. 16 (29): 55– 56, 1889. 20 Schinzinger: Das Karzinom der Mamma. München. med. Wchnschr. 52: 1724– 1725, 1905. 21 Taylor, G. W.: Evaluation of ovarian sterilization for breast cancer. Surg. Gynec. & Obst. 68: 452– 456, 1939. 22 Taylor, S. G., III: Endocrine ablation of disseminated mammary carcinoma. Surg. Gynec. & Obst. 115: 443– 448, 1962. 23 Thayssen, V. E.: Influence of castration by roentgen on carcinoma of breast. Acta radiol. 29: 189– 204, 1948. 24 Thomson, A.: Analysis of cases in which oophorectomy was performed for inoperable carcinoma of breast. Brit. M. J. 2: 1538– 1541, 1902. 25 Treves, N., and Finkbeiner, J. A.: Evaluation of therapeutic surgical castration in treatment of metastatic, recurrent, and primary inoperable mammary carcinoma in women; analysis of 191 patients. Cancer 11: 421– 438, 1958. Citing Literature Volume17, Issue9September 1964Pages 1197-1202 ReferencesRelatedInformation