Anthracycline Antibiotics in Cancer Therapy : Proceedings of the International Symposium on Anthracycline Antibiotics in Cancer Therapy, New York, New York, 16–18 September 1981

F. M. MUGGIA When faced with the inadequacies of current cancer treatment, we prefer to look at what the future may hold. Quite often, we take for granted the past, preferring research into totally new areas. However, the persistent development of fertile soil may yield surprising rewards for those who choose to build on the knowledge of the past--hence, this symposium on anthracycline antibiotics. Although the anthracycline antibiotics represent much of the present and future of cancer treatment, their actual use c stretches back barely two decades to the pioneering efforts of Aurelio Di Marco, who characterized the antitumor properties of daunomycin and adriamycin. \* The clinical application of these two compounds heralded a decade of excitement among oncologists dealing with pediatric tumors, breast cancer, leukemias, and lymphomas, and opened new hope for patients afflicted with sar­ comas and a variety of other tumors that had been deemed - sistant to chemotherapy. These successes were tempered with the realization that the antitumor effect of anthracyclines could be achieved at times only at the very high price of risking cardiac decompensation and, almost invariably, with the occurrence of alopecia and other acute toxicities. This record of past achievements and problems has slowly given way to a present increasingly illuminated by our ability to modify the distressing toxicities of these agents. Detailed clinical studies supplemented by ingenious laboratory models have gradually elucidated mechanisms and risk factors im­ plicated in the cardiomyopathy. Front Matter....Pages i-xx Front Matter....Pages 1-1 Introduction....Pages 3-12 Antitumor Activity of Anthracyclines: Experimental Studies....Pages 13-29 Anthracycline Antitumor Antibiotics: Their Carcinogenicity and their Mutagenicity....Pages 30-49 The Immunological Activity of Anthracyclines....Pages 50-68 Front Matter....Pages 69-69 Introduction....Pages 71-73 Doxorubicin and Related Compounds. I. Physicochemical Characterization of the DNA Complex....Pages 74-85 Consequences of DNA Intercalation: Protein-Associated DNA Strand Breaks....Pages 86-96 Free Radical Damage....Pages 97-102 Intracellular, Intranuclear, and Subchromosomal Localization of Anthracycline Antibiotics....Pages 103-116 Effects of Anthracyclines on Macromolecules and their Syntheses....Pages 117-124 Biotransformations of Anthracyclines in the Smooth Endoplasmic Reticulum of Rat Liver....Pages 125-131 Transport and Storage of Anthracyclines in Experimental Systems and Human Leukemia....Pages 132-146 Calcium Flux and Metabolism in the Pigeon Heart Following Doxorubicin Treatment: A Study of Acute Changes....Pages 147-158 The Role of Acute Lipid Peroxidation in Doxorubicin Cardiotoxicity....Pages 159-164 The Physicochemical Properties and Transmembraneous Transport of Doxorubicin....Pages 165-172 Front Matter....Pages 173-173 Introduction....Pages 175-178 Doxorubicin and Related Compounds. II. Structure-Activity Considerations....Pages 179-189 Second-Generation Anthracyclines....Pages 190-204 Factors in Selection of New Anthracyclines....Pages 205-219 Implications of Free Radical Activation for Improved Anthracycline Therapy....Pages 220-239 Front Matter....Pages 173-173 Screening for Second-Generation Anthracyclines in a Human Tumor Cloning System....Pages 240-246 Activity of Anthracyclines on Human Tumors In Vitro ....Pages 247-253 Pharmacologic and Therapeutic Characteristics of Anthracycline Liposome Preparation....Pages 254-273 N -L-Leucyl Derivatives of Anthracyclines: Toxic and Chemotherapeutic Properties....Pages 274-281 Alternative Methods of Drug Delivery....Pages 282-291 Front Matter....Pages 293-293 Introduction....Pages 295-296 The Role of Free Radical Damage in the Genesis of Doxorubicin Cardiac Toxicity....Pages 297-305 Screening for Cardiotoxic Properties....Pages 306-316 Role of Oxygen Radical Formation in Anthracycline Cardiac Toxicity....Pages 317-330 Morphologic Assessment of Cardiac Lesions Caused by Anthracyclines....Pages 331-347 Cardiac Monitoring of Patients Receiving Anthracyclines....Pages 348-351 Reduction of Adriamycin Cardiac Toxicity by Schedule Manipulation....Pages 352-357 Rationale and Design of a Trial to Evaluate the Cardiotoxocity of Weekly Schedules of Adriamycin, with Endomyocardial Biopsy used as an End Point....Pages 358-362 Anthracyclines in Cancer Chemotherapy....Pages 363-378 Front Matter....Pages 379-379 Introduction....Pages 381-383 Doxorubicin in the 1980s: Is There Still Room for Clinical Investigation?....Pages 384-397 A Phase I/II Study of 6-Hour and 24-Hour Intravenous Infusions of Doxorubicin....Pages 398-410 Intravesical Chemotherapy in the Treatment and Prophylaxis of Bladder Tumors, with Special Reference to Doxorubicin....Pages 411-421 Intraperitoneal Adriamycin in Ovarian Cancer....Pages 422-431 Role of Adriamycin in Breast Cancer and Sarcomas....Pages 432-444 Front Matter....Pages 379-379 Prospects for Doxorubicin in Adjuvant Breast Cancer Trials....Pages 445-454 Clinical Evaluation of 4′-Epi Doxorubicin and 4-Demethoxy Daunorubicin....Pages 455-465 Front Matter....Pages 467-467 Introduction....Pages 469-470 The Anthracyclines--A Historical Perspective....Pages 471-494 Phase-I Trial with 4-Demethoxydaunorubicin....Pages 495-503 Clinical Studies of New Anthracycline Analogs....Pages 504-514 A Clinical Overview of Aclacinomycin A in Japan....Pages 515-526 The Clinical Pharmacology of Aclacinomycin-A....Pages 527-540 Phase II Evaluation of N-Trifluoroacetyladriamycin-14-Valerate (AD 32)....Pages 541-548 Preliminary Experience with Marcellomycin: Preclinical and Clinical Aspects....Pages 549-561 Preliminary Phase II Experience with 4′Epidoxorubicin....Pages 562-567