Cancer Chemotherapy and Selective Drug Development: Proceedings of the 10th Anniversary Meeting of the Coordinating Committee for Human Tumour Investigations, Brighton, England, October 24–28, 1983

Front Matter....Pages i-xxv
Front Matter....Pages 1-1
Clinical Drug Resistance....Pages 5-11
New Therapies With Old Drugs....Pages 13-17
Antimetabolite Combinations Possessing Enhanced Efficacy....Pages 19-32
Mismatched Bone Marrow Transplantation....Pages 33-41
Prospects for Immunotherapy....Pages 43-45
Platinum Analogs....Pages 49-53
Mitoxantrone: A Promising New Agent for the Treatment of Human Cancer....Pages 55-63
Current Clinical Progress — Podophyllotoxins....Pages 65-69
Pharmacology of Nitrosourea Anticancer Agents....Pages 71-75
Current Clinical Progress with New Agents: Alkylating Agents....Pages 77-82
Interferon....Pages 83-87
Chemotherapy of Lung Cancer....Pages 91-94
Hormone-Chemotherapy in Treatment of Advanced Breast Cancer....Pages 95-104
Chemotherapy of Ovarian Cancer....Pages 105-109
Obstacles to Improved End-Results in Head and Neck Cancer....Pages 111-115
Treatment of Disseminated Malignant Lymphoma....Pages 117-122
Malignant Disease in Childhood....Pages 123-133
Chemotherapy of Disseminated Testicular Cancer....Pages 135-139
Rational Approach to the Management of Febrile Granulocytopenic Patients....Pages 141-144
Front Matter....Pages 145-145
Effective Use of Narcotic Analgesics....Pages 147-151
Front Matter....Pages 145-145
A Double Blind Cross-Over Study of Two Oral Formulations of Morphine....Pages 153-158
Non-Narcotics and Co-Analgesics....Pages 159-163
Advanced Cancer: Oncologist, Family Doctor, or Hospice?....Pages 165-171
Why Do Cancer Patients Vomit?....Pages 173-176
Cancer, Vomiting, and Gut Motility....Pages 177-182
The Medical Management of Malignant Bowel Obstruction....Pages 183-188
Etiology of Chemotherapy-Induced Vomiting....Pages 189-193
The Management of Nausea and Vomiting Caused by Anticancer Chemotherapy....Pages 195-203
Front Matter....Pages 205-205
Experimental Models and their Predictive Value in New Drug Development: A Critical Appraisal: I. Toxicity Models.....Pages 209-214
 In Vivo Antitumor Models and Drug Development....Pages 215-219
Assays for Clonogenic Human Tumour Cells in Experimental and Clinical Chemotherapy....Pages 221-225
Mechanisms of Resistance to Anticancer Agents....Pages 227-230
The Role of Pharmacokinetics in Drug Design and Use....Pages 231-233
Novel Structures in Development....Pages 235-239
Hypoxia-Mediated Drugs for Radio- and Chemotherapy....Pages 241-247
Induction of Cell Differentiation as a Target for Cancer Therapy....Pages 251-255
Complement Lysis of Tumour Cells Induced by Univalent Antibodies....Pages 257-262
Antibody-Toxin Conjugates as Anti-Cancer Agents....Pages 263-267
Biological Response Modifiers as Anticancer Agents....Pages 271-276
Prostaglandins and Cancer — Therapeutic Potential....Pages 277-281
Front Matter....Pages 205-205
The Therapeutic Potential of Lymphokines in Human Cancer....Pages 283-287
The Interleukins....Pages 289-293
The Role of Polyamines in Cell Differentiation....Pages 295-299
Polyamines, Immune Response and Tumour Growth Control....Pages 301-305
Potential Use of Retinoids in Cancer Prevention and Treatment....Pages 307-311
Front Matter....Pages 313-313
Inosine 5’-Phosphate Dehydrogenase as a Target for Cancer Chemotherapy. Results with 3-Deazaguanine, Tiazofurin and 2- β -D-Ribofuranosylselenazole-4-Carboxamide (PD-111232)....Pages 315-320
Antitumour Activity and Pharmacology of CCRG 81010 (NSC 353451, M&B 39565, 8-carbamoyl-3-(1-chloroethyl)imidazo [5,1-d]-1,1,3,5-tetrazin-4(3H)-one)....Pages 321-325
New Pyrimidine Nucleosides with Potent Antiviral Activity....Pages 327-331
Lipophilic Inhibitors of Dihydrofolate Reductase....Pages 333-337
Review of Phase I-II Clinical Trials with Vinzolidine (VZL), A New Orally Active Semisynthetic Vinblastine Derivative....Pages 339-343
New Developments in Anthracyclines....Pages 345-349
Nitrosoureas-Still a Challenge for Developmental Cancer Chemotherapy....Pages 351-356
Further Objectives in the Development of Platinum Drugs....Pages 357-362
Front Matter....Pages 363-363
The Structure of Active Genes and HMG Proteins in Normal and Transformed Cells....Pages 365-369
Pretreatment of Human Colon Tumor Cells with DNA Methylating Agents Inhibits their Ability to Prevent Chloroethylnitrosourea-Induced DNA Interstrand Crosslinking....Pages 371-375
Structural Requirements for DNA Intercalation and their Relevance to Drug Design....Pages 377-381
Dialkanesulphonates and Chromatin....Pages 383-387
DNA Repair Characteristics of Walker Rat Carcinoma Cells Sensitive and Resistant to Cis -Diamminedichloroplatinum(II) (Cisplatin) and Difunctional Alkylating Agents....Pages 389-394
Is Alkylating Agent “Priming” a DNA Repair Phenomenon?....Pages 395-400
DTIC Induces Damage in Melanoma DNA During Semi-Conservative DNA Synthesis....Pages 401-405
Front Matter....Pages 363-363
The Non-Random Binding of Chlorambucil to DNA in Chromatin....Pages 407-411
Alkylating Antitumour Agents Decrease Histone Acetylation in Ehrlich-Ascites Tumour Cells....Pages 413-417
Influence of the Nuclear Matrix on Nuclear Structure and Response to Anticancer Drugs....Pages 419-424
Cytotoxicity of a Steroid-Linked Mustard (Estramustine) through Non-DNA Targets....Pages 425-429
Potentiation of Cytotoxicity by Inhibitors of Nuclear ADP-Ribosyl Transferase....Pages 431-435
Front Matter....Pages 437-437
Adjuvant Tamoxifen Treatment in Operable Breast Cancer. Should the Treatment Continue for Many Years?....Pages 439-444
Adjuvant Hormonal Therapy of Breast Cancer....Pages 445-449
New Approaches to the Use of Endocrine Therapy in Breast Cancer....Pages 451-455
The Pharmacology of a New Antiestrogen....Pages 457-461
In Vitro Systems for Evaluating Anti-Endocrine Agents....Pages 463-468
Experience of the LHRH Analogue, ICI 118,430, in Carcinoma of the Prostate....Pages 469-473
Complete Androgen Neutralization is Most Important in the Treatment of Prostate Cancer....Pages 475-479
Aminoglutethimide (Orimeten R ): The Present and the Future....Pages 481-483
The Development of New Anti-Endocrine Type Drugs....Pages 485-489
Antiestrogenic Action of Tamoxifen Derivatives in the Human Mammary Carcinoma Cell Line MCF-7....Pages 491-496
Nuclear Estrogen Receptors in Human Tumours of Breast and Uterus....Pages 497-501
Activation and Translocation of Estradiol Receptors in Nitrosomethylurea-Induced Mammary Carcinomas of Rats....Pages 503-507
Hormone Receptors in Gynecological Tumours and their Relevance for Therapeutic Management....Pages 509-511
Front Matter....Pages 513-513
Pretherapeutic in Vitro Prediction of Human Tumour Drug Response....Pages 517-517
Continuous Cell Lines as an Experimental Model for Bladder Cancer Chemotherapy....Pages 517-517
Front Matter....Pages 513-513
Chemical and Biological Properties and Mode of Action of 8-Carbamoyl-3-(2-Chloroethyl)Imidazo [5,1-d]-1,2,3,5-Tetrazin-4(3H)-One, A Novel Broad Spectrum Antitumour Agent....Pages 518-518
Lycurim in Combination Chemotherapy with 3,4,5-Trihydroxybenzo Hydroxamic Acid in Vitro....Pages 518-518
Phenotypic and Genotypic Changes Induced by Thioproline in Cancer Cells in Tissue Culture. Guidelines for Clinical Studies of the Drug....Pages 519-519
Use of Mesna in Reducing Bladder Toxicity....Pages 519-519
Normal Tissue Protection during High-Dose Chemo/Radiotherapy by a “Priming Dose” of Cyclophosphamide....Pages 520-520
5-Acetoxy-2-(4-Acetoxyphenyl)-1-Ethyl-3-Methylindole (D 16726): Preclinical Evaluation of a New Mammary Tumour Inhibiting Drug....Pages 520-520
Rolin Enhancing Effect Upon in Vitro PHA-Proliferation Of Normal Human Peripheral Blood Lymphocytes....Pages 521-521
DTIC: Towards an Appropriate Alternative....Pages 521-521
Drug Resistance of Human Glioma Cell Lines in Culture — The Role of Membrane Transport....Pages 522-522
Lethal and Kinetic Effects of AMSA in a Range of Human Tumour Cell Lines and its Value in Overcoming Induced Drug Resistance in a Series of Murine L5178Y Lymphoma Sublines in Vitro ....Pages 522-522
A Novel HPLC Procedure for Measurement of 6-Mercaptopurine in Plasma....Pages 523-523
Potentiation of the Cytotoxicity of Antibody-Toxin a Chain Conjugates....Pages 523-523
The Effect of Inhibitors of Poly(ADP-Ribose)Polymerase Activity on the Cytotoxic Action of Bifunctional Alkylating Agents and Radiation....Pages 524-524
Characterisation of a Murine Renal Cell Carcinoma Model Potentially Useful in Selecting New Chemotherapeutic Agents....Pages 524-524
Perturbation of S-Adenosylhomocysteine (SAH) and S-Adenosylmethionine (SAM) Levels Following 2’-Deoxycoformycin (dCf) and 2’-Deoxyadenosine (AdR) Administration....Pages 525-525
The Development of Resistance to Methotrexate in a Human Leukaemia (AML) Growing in Nude Mice....Pages 525-525
Inhibitors of Thymidine (TdR) Salvage....Pages 526-526
Studies on the Mechanism of CB 3717 Induced Hepatotoxicity....Pages 526-526
Studies Relating to the Reversal of the Cytotoxicity of the Thymidylate Synthetase Inhibitor CB 3717....Pages 527-527
Studies with Mutant L1210 Cell Lines that have Acquired Resistance to CB 3717....Pages 527-527
Front Matter....Pages 513-513
PAC Polychemotherapy of Stage III + IV Ovarian Carcinoma....Pages 531-531
Weekly Low Dose 4 Epi-Adriamycin-Effective Single Agent Chemotherapy for Advanced Breast Cancer with Low Toxicity....Pages 531-531
Combination Treatment of Malignant Gliomas with Dibromodulcitol (DBD)....Pages 532-532
Initial Clinical Sudies with Iproplatin (CHIP, JM9)....Pages 532-532
Tamoxifen Induced Fluorescence: Spectrofluorimetric Study and Clinical Applications of the Ion-Pair Eosin Tamoxifen....Pages 533-533
EB-Virus Antibody Titers in Two Sisters with Nasopharyngeal Carcinoma and in Several Members of their Family....Pages 533-533
Loco-Regional Chemotherapy with Adriamycin — Intravesical, Intrapleural, and Intrahepatic Administration....Pages 534-534
Etoposide (VP 16–213) as a Fourth Drug in Combination with BVP for Treating Metastatic Germ Cell Tumours....Pages 534-534
Investigations on Leucovorin Rescue after Methotrexate Treatment of Human Osteosarcoma Cells in vitro ....Pages 535-535
Early Clinical Studies with CB 3717 (N-(4-(N-((2-Amino-4-Hydroxy-6-Quinazolinyl)Methyl)Prop-2-Ynylamino)Benzoyl)-L-Glutamic Acid) at the Royal Marsden Hospital....Pages 535-535
DNA Repair Enzymes and Crosslinks: Prevention of BCNU Inter-Strand Crosslinking in vitro by 06-Methyltransferase....Pages 539-539
CIS-Diamminedichloroplatinum Toxicity and DNA Crosslinking in Human Melanoma and Lymphoblast Cells....Pages 539-539
Experimental Trial of New Alkylating Hexitols....Pages 540-540
Sites and Extents of Alkylation in Tumour Cell DNA and their Relation to Antitumour Effects of Dibromodulcitol and Dianhydrogalactitol....Pages 540-540
Hexamethylmelamine: Metabolic Activation and Cytotoxicity....Pages 541-541
Melanogenesis in Human Malignant Melanoma Xenografts....Pages 541-541
DNA Cross-Linking and Cytotoxicity in Normal and Transformed Human Cells Treated in vitro with M&B 39565....Pages 542-542
 In Vivo Pharmacokinetics of Daunorubicin in Bone Marrow in Adult Acute Nonlymphocytic Leukaemia....Pages 545-545
Pharmacologic Characterization of Teroxirone (Henkel Compound) in Animals and Humans....Pages 545-545
Pharmacokinetics and Toxicity of VP 16 (Etoposide) in Patients with Gestational Choriocarcinoma and Malignant Teratoma....Pages 546-546
Front Matter....Pages 513-513
Tissue Distribution and Myelotoxicity of Daunomycin in Normal and Leukemic Rats: Rapid Bolus Injection versus Continuous Infusion....Pages 546-546
Metabolism of 4-Hydroxyandrostene-3, 17-Dione by Rat Liver....Pages 547-547
Enzyme Inhibition Studies with Derivatives of Aminoglutethimide....Pages 547-547
The Species Dependent Pharmacokinetics of DTIC....Pages 548-548
Preliminary Studies on the Metabolism and Pharmacokinetics of the Dialkylphenyltriazenes....Pages 548-548
The Role of Glutathione and Glutathione S-Transferases in Acquired Drug Resistance....Pages 549-549
Disposition of Tricyclic Nucleoside 5’-Phosphate (TCN-P, NSC 280594) in Man and Rat....Pages 549-549
Circadian Variation in the Pharmacokinetics of Some Cytotoxic Drugs and Synthetic Steroids....Pages 550-550
Antitumour and Pharmacokinetic Studies with Platinum Coordination Complexes Following Oral Administration....Pages 550-550
Back Matter....Pages 551-585