Nitrosoureas
Current Status and New Developments
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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.
Table of Contents
Contributors
Preface
Section 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
References
Section 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
Product details
- No. of pages: 436
- Language: English
- Copyright: © Academic Press 1981
- Published: January 1, 1981
- Imprint: Academic Press
- eBook ISBN: 9781483219448