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Nitrosoureas

Current Status and New Developments

1st Edition - January 1, 1981

Editors: Archie W. Prestayko, Laurence H. Baker, Stanley T. Crooke

eBook ISBN:

9 7 8 - 1 - 4 8 3 2 - 1 9 4 4 - 8

Nitrosoureas: Current Status and New Developments covers the preclinical and clinical status of nitrosoureas. The book presents preclinical studies on the development of the… Read more

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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.

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