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. Conclusions References 20. Chemotherapy of Recurrent Brain Tumors I. Introduction II. Methods III. Results of Treatment IV. Conclusion References 21. Lipid-Soluble Nitrosoureas in the Management of Children with Primary and Recurrent Brain Tumors I. Introduction II. Clinical Results III. Toxicities IV. Conclusion References 22. Adjuvant Therapy of Brain Tumors with Nitrosoureas I. Introduction II. Clinical Trials III. Conclusion References 23. Clinical Use of Nitrosoureas in Gastrointestinal Cancer I. Introduction II. Results III. Future Directions References 24. A Randomized Comparative Trial in Colorectal Cancer I. Introduction II. Patients and Methods III. Results IV. Discussion References 25. Clinical Use of Nitrosoureas in Patients with Malignant Melanoma: A Review I. Introduction II. Results III. Discussion References 26. Nitrosoureas in the Treatment of Multiple Myeloma I. Introduction II. Methods III. Results IV. Discussion References 27. Clinical Trials of Nitrosoureas in Metastatic Sarcomas I. Introduction II. Materials and Method III. Results IV. Discussion References 28. High-Dose Nitrosourea (BCNU) and Autologous Bone Marrow Transplantation: A Phase I Study I. Introduction II. Materials and Methods III. Results IV. Discussion References 29. Amphotericin B: Interactions with Nitrosoureas and Other Antineoplastic Drugs I. Introduction II. Preclinical Studies III. Clinical Studies IV. Conclusions References 30. Activity of Nitrosoureas on Human Tumors In Vitro I. Introduction II. Materials and Methods III. Results IV. Discussion References 31. Streptozotocin I. Introduction II. Results III. Conclusion References 32. Phase I and II Studies of PCNU I. Introduction II. Background III. Phase I Trials of PCNU IV. Clinical Responses V. Pharmacological Information VI. Conclusion References 33. Chlorozotocin: Clinical Trials I. Introduction II. Phase I Trials III. Clinical Pharmacology IV. Phase II Trials V. Conclusion References 34. Current Status of Nitrosoureas under Development in Japan I. Introduction II. ACNU III. GANU IV. MCNU References 35. Design of Clinical Trials with Nitrosourea I. Introduction II. Structure-Activity/Toxicity Relationships III. Clinical Trials: Past, Present, and Future IV. Future Clinical Trials V. Conclusion References