Cancer Chemotherapy and Selective Drug Development

I: Advances in Cancer Treatment.- 1. New Approaches to Old Problems.- Clinical drug resistance.- New therapies with old drugs.- Antimetabolite combinations possessing enhanced efficacy.- Mismatched bone marrow transplantation.- Prospects for immunotherapy.- 2. Current Clinical Progress with New Agents.- Platinum analogs.- Mitoxantrone: A promising new agent for the treatment of human cancer.- Current clinical progress - podophyllotoxins.- Pharmacology of nitrosourea anticancer agents.- Current clinical progress with new agents: alkylating agents.- Interferon.- 3. Drug Treatment of Specific Cancers.- Chemotherapy of lung cancer.- Hormone-chemotherapy in treatment of advanced breast cancer.- Chemotherapy of ovarian cancer.- Obstacles to improved end-results in head and neck cancer.- Treatment of disseminated malignant lymphoma.- Malignant disease in childhood.- Chemotherapy of disseminated testicular cancer.- Rational approach to the management of febrile granulocytopenic patients.- II: Control of Pain and Vomiting in Cancer Patients.- Effective use of narcotic analgesics.- A double-blind cross-over study of two oral formulations of morphine.- Non-narcotics and co-analgesics.- Advanced cancer: Oncologist, family doctor or hospice?.- Why do cancer patients vomit?.- Cancer, vomiting and gut motility.- The medical management of malignant bowel obstruction.- Etiology of chemotherapy-induced vomiting.- The management of nausea and vomiting caused by anticancer chemotherapy.- III: Perspective in New Drug Development.- 1. Problems in Achieving Drug Selectivity.- Experimental models and their predictive value in new drug development: A critical appraisals I. Toxicity models.- In vivo antitumour models and drug development.- Assays for clonogenic human tumour cells in experimental and clinical chemotherapy.- Mechanisms of resistance to anticancer agents.- The role of pharmacokinetics in drug design and use.- Novel structures in development.- Hypoxia-mediated drugs for radio- and chemotherapy.- 2. Targetted Chemotherapy.- Induction of cell differentiation as a target for cancer therapy.- Complement lysis of tumour cells induced by univalent antibodies.- Antibody-toxin conjugates as anticancer agents.- 3. Regulatory Molecules in Chemotheraphy.- Biological response modifiers as anticancer agents.- Prostaglandins and cancer - therapeutic potential.- The therapeutic potential of lymphokines in human cancer.- The interleukins.- The role of polyamines in cell differentiation.- Polyamines, immune response and tumour growth control.- Potential use of retinoids in cancer prevention and treatment.- IV: Design and Development of New Drugs.- Inosine 5'-phosphate dehydrogenase as a target for cancer chemotherapy.- Antitumour activity and pharmacology of CCRG 81010.- New pyrimidine nucleosides with potent antiviral activity.- Lipophilic inhibitors of dihydrofolate reductase.- Review of phase I-II clinical trials with vinzolidine (VZL), a new orally active semisynthetic vinblastine derivative.- New developments in anthracyclines.- Nitrosoureas - still a challenge for developmental cancer chemotherapy.- Further objectives in the development of platinum drugs.- V: Chromatin as a Target in Cancer Chemotherapy.- The structure of active genes and HMG proteins in normal and transformed cells.- Pretreatment of human colon tumour cells with DNA methylating agents inhibits their ability to prevent chloroethylnitrosourea-induced DNA interstrand crosslinking.- Structural requirements for DNA intercalation and their relevance to drug design.- Dialkanesulphonates and chromatin.- DNA repair characteristics of Walker rat carcinoma cells sensitive and resistant to cis-diamminedichloroplatinum(II) (cisplatin) and difunctional alkylating agents.- Is alkylating agent "Priming" a DNA repair phenomenon?.- DTIC induces damage in melanoma DNA during semi-conservative DNA synthesis.- The non-random binding of chlorambucil to DNA in chromatin.- Alkylating antitumour agents decrease histone acetylation in Ehrlich ascites tumour cells.- Influence of the nuclear matrix on nuclear structure and response to anticancer drugs.- Cytotoxicity of a steroid-linked mustard (Estramustine) through non-DNA targets.- Potentiation of cytotoxicity by inhibitors of nuclear ADP-ribosyl transferase.- VI: Endocrine Therapy.- Adjuvant tamoxifen treatment in operable breast cancer. Should the treatment continue for many years?.- Adjuvant hormonal therapy of breast cancer.- New approaches to the use of endocrine therapy in breast cancer.- The pharmacology of a new antiestrogen.- In vitro systems for evaluating anti-endocrine agents.- Experience of the LHRH analogue, ICI 118,430, in carcinoma of the prostate.- Complete androgen neutralization is most important in the treatment of prostate cancer.- Aminoglutethimide (OrimetenR): The present and the future.- The development of new anti-endocrine type drugs.- Antiestrogenic action of tamoxifen derivatives in the human mammary carcinoma cell line MCF-7.- Nuclear estrogen receptors in human tumours of breast and uterus.- Activation and translocation of estradiol receptors in nitrosomethylurea-induced mammary carcinomas of rats.- Hormone receptors in gynecological tumours and their relevance for therapeutic management.- Abstracts of Proffered Papers and Posters.- 1. New Agents: Experimental Studies.- Pretherapeutic in vitro prediction of human tumour drug response.- Continuous cell lines as an experimental model for bladder cancer chemotherapy.- 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.- Lycurim in combination chemotherapy with 3,4,5-trihydroxybenzo hydroxamic acid in vitro.- Phenotypic and genotypic changes induced by thioproline in cancer cells in tissue culture.- Use of MESNA in reducing bladder toxicity.- Normal tissue protection during high-dose chemo/radiotherapy by a "priming dose" of cyclophosphamide.- 5-Acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole (D 16726): Preclinical evaluation of a new mammary tumour inhibiting drug.- Rolin enhancing effect upon in vitro PHA-proliferation of normal human peripheral blood lymphocytes.- DTIC: Towards an appropriate alternative.- Drug resistance of human glioma cell lines in culture - the role of membrane transport.- 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.- A novel HPLC procedure for measurement of 6-mercaptopurine in plasma.- Potentiation of the cytotoxicity of antibody-Toxin A chain conjugates.- The effect of inhibitors of poly(ADP-ribose)polymerase activity on the cytotoxic action of bifunctional alkylating agents and radiation.- Characterisation of a murine renal cell carcinoma model potentially useful in selecting new chemotherapeutic agents.- Perturbation of S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) levels following 2?-deoxycoformycin (dCf) and 2'-deoxyadenosine (AdR) administration.- The development of resistance to methotrexate in human leukaemia (AML) growing in nude mice.- Inhibitors of thymidine (TdR) salvage.- Studies on the mechanism of CB 3717 induced hepatotoxicity.- Studies relating to the reversal of the cytotoxicity of the thymidylate synthetase inhibitor CB 3717.- Studies with mutant L1210 cell lines that have acquired resistance to CB 3717.- 2. New Agents/Combinations: Clinical Studies.- PAC polychemotherapy of stage III + IV ovarian carcinoma.- Weekly low dose 4 epi-adriamycin-effective single agent chemotherapy for advanced breast cancer with low toxicity.- Combination treatment of malignant gliomas with dibromodulcitol.- Initial clinical studies with iproplatin (CHIP, JM9).- Tamoxifen induced fluorescence: Spectrofluorimetric study and clinical applications of the ion-pair eosin tamoxifen.- EB-virus antibody titers in two sisters with nasopharyngeal carcinoma and in several members of their family.- Loco-regional chemotherapy with adriamycin - intravesical, intrapleural and intrahepatic administration.- Etoposide (VP 16-213) as a fourth drug in combination with BVP for treating metastatic germ cell tumours.- Investigations on leucovorin rescue after methotrexate treatment of human osteosarcoma cells in vitro.- Early clinical studies with CB 3717 at the Royal Marsden Hospital.- 3. New Agents: Cytotoxic Mechanisms.- DNA repair enzymes and crosslinks: Prevention of BCNU inter-strand crosslinking in vitro by 06-methyltransferase.- Cis-diamminedichloroplatinum toxicity and DNA crosslinking in human melanoma and lymphoblast cells.- Experimental trial of new alkylating hexitols.- Sites and extents of alkylation in tumour cell DNA and their relation to antitumour effects of dibromodulcitol and dianhydrogalactitol.- Hexamethylmelamine: Metabolic activation and cytotoxicity.- Melanogenesis in human malignant melanoma xenografts.- DNA cross-linking and cytotoxicity in normal and transformed human cells treated in vitro with M&B 39565.- 4. New Agents: Metabolism and Pharmacokinetics.- In vivo pharmacokinetics of daunorubicin in bone marrow in adult acute nonlymphocytic leukaemia.- Pharmacologic characterisation of teroxirone (Henkel compound) in animals and humans.- Pharmacokinetics and toxicity of VP16 (etoposide) in patients with gestational choriocarcinoma and malignant teratoma.- Tissue distribution and myelotoxicity of daunomycin in normal and leukaemic rats: Rapid bolus injection versus continuous infusion.- Metabolism of 4-hydroxyandrostene-3,17-dione by rat liver.- Enzyme inhibition studies with derivatives of aminoglutethimide.- The species dependent pharmacokinetics of DTIC.- Preliminary studies on the metabolism and pharmacokinetics of the dialkylphenyltriazenes.- The role of glutathione and glutathione S-transferases in acquired drug resistance.- Disposition of tricyclic nucleoside 5?-phosphate (TCN-P, NSC 280594) in man and rat.- Circadian variation in the pharmacokinetics of some cytotoxic drugs and synthetic steroids.- Antitumour and pharmacokinetics studies with platinum coordination complexes following oral administration.- Author Index.