The addition of chemotherapy as an effective means to treat cancer has had a major impact on selected human malignancies. Due to a general inability to dif ferentiate between normal and neoplastic cells, little selectivity exists in currently used oncolytic drugs. Consequently, significant toxicity to the patient is expected when systemic cancer chemotherapy is chosen as an appropriate therapeutic in tervention. Much of this toxicity, such as damage to the bone marrow, gastroin testinal tract, or hair follicles, is predictable based upon the fact that anticancer drugs kill actively dividing cells. These types of toxicities, while serious, are usually manageable and reversible and are, therefore, not often considered to be dose limiting. Unfortunately, several of the most important anticancer drugs also damage tissues in which the growth fraction is relatively small. Such toxicities can not be predicted based on the chemical structure of the drugs, are often not detected in preclinical studies, and are encountered frequently for the first time in clinical studies. Further, unlike most of the proliferative-dependent toxicities, the unpre dicted toxicities are usually irreversible or only partially reversible upon cessation of drug administration. Because of this, the unpredicted toxicities are referred to as dose limiting. They represent a significant barrier to the ultimate efficacy of several of our most important anticancer drugs.
Table of ContentsKeynote Address.- The Irrelevant Toxicities of Anticancer Drugs.- Section I: Anthracycline Induced Cardiotoxicity.- Overview.- Role of Iron in Anthracycline Action.- Role of Reactive Oxygen Production in Doxorubicin Cardiac Toxicity.- Adriamycin Cardiac Toxicity An Assessment of Approaches to Cardiac Monitoring and Cardioprotection.- Pretreatment with ICRF-187 Protects Against the Chronic Cardiac Toxicity Produced by Very Large Cumulative Doses of Doxorubicin in Beagle Dogs.- A Trial of ICRF-187 to Selectively Protect Against Chronic Adriamycin Cardiac Toxicity: Rationale and Preliminary Results of a Clinical Trial.- Section II: Bleomycin Induced Pulmonary Toxicity.- Overview.- Base Propenals and the Toxicity of Bleomycin.- Bleomycin Induced Lung Injury.- Immunoregulation of Growth Factor Release in Bleomycin Induced Lung Disease.- Pulmonary Toxicity of Anticancer Drugs: Alterations in Endothelial Cell Function.- Pulmonary Metabolic Inactivation of Bleomycin and Protection from Drug Induced Lung Injury.- Biochemical and Molecular Bases of Bleomycin Induced Pulmonary Fibrosis: Glucocorticoid Intervention.- Section III: Platinum Induced Nephrotoxicity.- Overview.- Factors Influencing the Formation and Persistence of Platinum-DNA Adducts in Tissues of Rats Treated with Cisplatin.- Cisplatin Nephrotoxicity: New Insights into Mechanism.- Experimental Approaches to Reducing Platinum Induced Kidney Toxicity.- High Dose Cisplatin with Hypertonic Saline: Toxicity and Therapeutic Results.- Section IV: Poster Presentations.- Titles and Authors.- Abstracts.- Author Index.