Nitrosoureas

Nitrosoureas: Current Status and New Developments covers the preclinical and clinical status of nitrosoureas. The book presents preclinical studies on the development of the nitrosoureas; combination chemotherapy with nitrosoureas plus other anticancer drugs against animal tumors; EORTC studies with novel nitrosoureas; and chemical decomposition of chloroethylnitrosoureas. The text also includes preclinical studies on the metabolism of nitrosoureas; DNA crosslinking and the origin of sensitivity to chloroethylnitrosoureas; modification of DNA and RNA bases; and carbamoylating activity of nitrosoureas. Clinical studies on subacute and chronic toxicities associated with nitrosourea therapy; the toxicity of high-dose BCNU with autologous marrow support; and the clinical pharmacology of the nitrosoureas are also considered. The book further tackles clinical studies on nitrosoureas in the therapy of Hodgkin's disease; nitrosourea-containing combinations in small-cell lung cancer; adjuvant therapy of brain tumors with nitrosoureas; and clinical use of nitrosoureas in gastrointestinal cancer. Oncologists, toxicologists, biochemists, pharmacologists, and other scientists working in drug development will find the text invaluable.

ContributorsPrefaceSection I: Preclinical Studies 1. The Development of the Nitrosoureas: A Study in Congener Synthesis I. N-Nitroso Function II. Chloroethyl Moiety III. Antitumor Activity in Animal Tumors IV. Conclusion References 2. Combination Chemotherapy with Nitrosoureas plus Other Anticancer Drugs against Animal Tumors I. Introduction II. Biologic Activity of Nitrosoureas in Combination with Other Anticancer Drugs III. Discussion IV. Summary References 3. EORTC Studies with Novel Nitrosoureas I. Introduction II. The Chemotherapeutic Activity of HECNU and Other NU Derivatives III. Selecting among NU Analogs IV. Conclusion References 4. Chemical Decomposition of Chloroethylnitrosoureas I. Introduction II. Decomposition of Nitrosoureas III. Decomposition of Other "Nitroso" Compounds IV. Conclusion References 5. Metabolism of Nitrosoureas I. Introduction II. Materials and Methods III. Results IV. Discussion V. Conclusions VI. References 6. DNA Crosslinking and the Origin of Sensitivity to Chloroethylnitrosoureas I. Introduction II. Materials and Methods III. Results IV. Discussion References 7. Modification of DNA and RNA Bases I. Introduction II. Materials and Methods III. Results IV. Discussion References 8. Carbamoylating Activity of Nitrosoureas I. Introduction II. Materials and Methods III. Results IV. Discussion References 9. Chromatin and Associated Nuclear Components as Potential Drug Targets I. Introduction II. Results III. Conclusion and Perspectives References 10. ADP-Ribosylation and DNA Repair as Induced by Nitrosoureas I. Introduction II. Results and Discussion III. Conclusion ReferencesSection II: Clinical Studies 11. Subacute and Chronic Toxicities Associated with Nitrosourea Therapy I. Introduction II. Pulmonary Toxicity III. Renal Toxicity IV. Other Adverse Effects V. Conclusions References 12. The Toxicity of High-Dose BCNU with Autologous Marrow Support I. Introduction II. Materials and Methods III. Results IV. Discussion V. Conclusion References 13.Clinical Pharmacology of the Nitrosoureas I. Introduction II. General Methods III. Pharmacokinetic Data IV. Discussion V. Conclusion References 14. Nitrosoureas in the Therapy of Hodgkin's Disease I. Introduction II. Materials and Methods III. Results IV. Discussion References 15. Hodgkin's Disease and Malignant Lymphomas I. Introduction II. Materials and Methods III. Results and Discussion IV. Conclusion References 16. CCNU in Combination Chemotherapy Programs for Small-Cell Lung Cancer I. Introduction and Background II. Materials and Methods III. Therapeutic Results IV. Toxicity V. Conclusion References 17. POCC versus POCC/VAM Therapy for Small-Cell Anaplastic (Oat Cell) Lung Cancer I.Introduction II.Methods III.Results IV.Discussion References 18. Nitrosourea-Containing Combinations in Small-Cell Lung Cancer I. Introduction II. Results III. Conclusions References 19. Nitrosourea-Containing Chemotherapy Regimens in the Treatment of Non-Small-Cell Lung Cancer I. Introduction II. Materials and Methods III. Results IV.