Prestayko / Baker / Crooke Nitrosoureas

Current Status and New Developments
1. Auflage 2013
ISBN: 978-1-4832-1944-8
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 436 Seiten, Web PDF

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.

Autoren/Hrsg.

Prestayko, Archie W.

Baker, Laurence H.

Crooke, Stanley T.

Inhaltsverzeichnis

1;Front Cover;1
2;Nitrosoureas: Current Status and New Developments;4
3;Copyright Page;5
4;Table of Contents;6
5;Contributors;14
6;Preface;20
7;Section I: PRECLINICAL STUDIES;22
7.1;Chapter 1. The Development of the Nitrosoureas: A Study in Congener Synthesis;24
7.1.1;I. N-Nitroso Function;24
7.1.2;II. Chloroethyl Moiety;25
7.1.3;III. Antitumor Activity in Animal Tumors;26
7.1.4;IV. Conclusion;29
7.1.5;References;29
7.2;Chapter 2. Combination Chemotherapy with Nitrosoureas plus Other Anticancer Drugs against Animal Tumors;30
7.2.1;I. Introduction;30
7.2.2;II. Biologic Activity of Nitrosoureas in Combination with Other Anticancer Drugs;31
7.2.3;III. Discussion;45
7.2.4;IV. Summary;45
7.2.5;References;46
7.3;Chapter 3. EORTC Studies with Novel Nitrosoureas;48
7.3.1;I. Introduction;48
7.3.2;II. The Chemotherapeutic Activity of HECNU and Other NU Derivatives;49
7.3.3;III. Selecting among NU Analogs;55
7.3.4;IV. Conclusion;62
7.3.5;ACKNOWLEDGMENT;62
7.3.6;References;62
7.4;Chapter 4. Chemical Decomposition of Chloroethylnitrosoureas;64
7.4.1;I. Introduction;64
7.4.2;II. Decomposition of Nitrosoureas;65
7.4.3;III. Decomposition of Other "Nitroso" Compounds;69
7.4.4;IV. Conclusion;69
7.4.5;References;69
7.5;Chapter 5. Metabolism of Nitrosoureas;72
7.5.1;I. Introduction;72
7.5.2;II. Materials and Methods;80
7.5.3;III. Results;83
7.5.4;IV. Discussion;85
7.5.5;V. Conclusions;86
7.5.6;VI. References;87
7.6;Chapter 6. DNA Crosslinking and the Origin of Sensitivity to Chloroethylnitrosoureas;90
7.6.1;I. Introduction;90
7.6.2;II. Materials and Methods;93
7.6.3;III. Results;94
7.6.4;IV. Discussion;102
7.6.5;References;103
7.7;Chapter 7. Modification of DNA and RNA Bases;106
7.7.1;I. Introduction;106
7.7.2;II. Materials and Methods;107
7.7.3;III. Results;108
7.7.4;IV. Discussion;112
7.7.5;References;115
7.8;Chapter 8. Carbamoylating Activity of Nitrosoureas;116
7.8.1;I. Introduction;116
7.8.2;II. Materials and Methods;119
7.8.3;III. Results;119
7.8.4;IV. Discussion;122
7.8.5;ACKNOWLEDGMENT;122
7.8.6;References;125
7.9;Chapter 9. Chromatin and Associated Nuclear Components as Potential Drug Targets;128
7.9.1;I. Introduction;128
7.9.2;II. Results;129
7.9.3;III. Conclusion and Perspectives;138
7.9.4;References;141
7.10;Chapter 10. ADP-Ribosylation and DNA Repair as Induced by Nitrosoureas;144
7.10.1;I. Introduction;144
7.10.2;II. Results and Discussion;146
7.10.3;III. Conclusion;162
7.10.4;ACKNOWLEDGMENT;162
7.10.5;References;162
8;SECTION II: CLINICAL STUDIES;166
9;Chapter 11. Subacute and Chronic Toxicities Associated with Nitrosourea Therapy;166
9.1;I. Introduction;166
9.2;II. Pulmonary Toxicity;167
9.3;III. Renal Toxicity;170
9.4;IV. Other Adverse Effects;172
9.5;V. Conclusions;174
9.6;ACKNOWLEDGMENT;174
9.7;References;174
10;Chapter 12. The Toxicity of High-Dose BCNU with Autologous Marrow Support;176
10.1;I. Introduction;176
10.2;II. Materials and Methods;177
10.3;III. Results;178
10.4;IV. Discussion;187
10.5;V. Conclusion;189
10.6;References;189
11;Chapter 13. Clinical Pharmacology of the Nitrosoureas;192
11.1;I. Introduction;192
11.2;II. General Methods;193
11.3;III. Pharmacokinetic Data;194
11.4;IV. Discussion;197
11.5;V. Conclusion;200
11.6;References;201
12;Chapter 14. Nitrosoureas in the Therapy of Hodgkin's Disease;202
12.1;I. Introduction;202
12.2;II. Materials and Methods;203
12.3;III. Results;205
12.4;IV. Discussion;215
12.5;References;218
13;Chapter 15. Hodgkin's Disease and Malignant Lymphomas;220
13.1;I. Introduction;220
13.2;II. Materials and Methods;220
13.3;III. Results and Discussion;221
13.4;IV. Conclusion;229
13.5;References;229
14;Chapter 16. CCNU in Combination Chemotherapy Programs for Small-Cell Lung Cancer;230
14.1;I. Introduction and Background;230
14.2;II. Materials and Methods;231
14.3;III. Therapeutic Results;235
14.4;IV. Toxicity;239
14.5;V. Conclusion;241
14.6;References;241
15;Chapter 17. POCC versus POCC/VAM Therapy for Small-Cell Anaplastic (Oat Cell) Lung Cancer;242
15.1;I.Introduction;242
15.2;II.Methods;243
15.3;III.Results;245
15.4;IV.Discussion;249
15.5;References;251
16;Chapter 18. Nitrosourea-Containing Combinations in Small-Cell Lung Cancer;254
16.1;I. Introduction;254
16.2;II. Results;255
16.3;III. Conclusions;263
16.4;References;264
17;Chapter 19. Nitrosourea-Containing Chemotherapy Regimens in the Treatment of Non-Small-Cell Lung Cancer;266
17.1;I. Introduction;266
17.2;II. Materials and Methods;266
17.3;III. Results;267
17.4;IV. Conclusions;277
17.5;References;277
18;Chapter 20. Chemotherapy of Recurrent Brain Tumors;280
18.1;I. Introduction;280
18.2;II. Methods;281
18.3;III. Results of Treatment;283
18.4;IV. Conclusion;288
18.5;ACKNOWLEDGMENT;288
18.6;References;288
19;Chapter 21. Lipid-Soluble Nitrosoureas in the Management of Children with Primary and Recurrent Brain Tumors;290
19.1;I. Introduction;290
19.2;II. Clinical Results;293
19.3;III. Toxicities;296
19.4;IV. Conclusion;296
19.5;ACKNOWLEDGMENT;296
19.6;References;297
20;Chapter 22. Adjuvant Therapy of Brain Tumors with Nitrosoureas;298
20.1;I. Introduction;298
20.2;II. Clinical Trials;299
20.3;III. Conclusion;304
20.4;References;304
21;Chapter 23. Clinical Use of Nitrosoureas in Gastrointestinal Cancer;306
21.1;I. Introduction;306
21.2;II. Results;307
21.3;III. Future Directions;311
21.4;References;312
22;Chapter 24. A Randomized Comparative Trial in Colorectal Cancer;314
22.1;I. Introduction;314
22.2;II. Patients and Methods;315
22.3;III. Results;316
22.4;IV. Discussion;319
22.5;References;320
23;Chapter 25. Clinical Use of Nitrosoureas in Patients with Malignant Melanoma: A Review;322
23.1;I. Introduction;322
23.2;II. Results;324
23.3;III. Discussion;330
23.4;References;332
24;Chapter 26. Nitrosoureas in the Treatment of Multiple Myeloma;334
24.1;I. Introduction;334
24.2;II. Methods;335
24.3;III. Results;335
24.4;IV. Discussion;343
24.5;References;344
25;Chapter 27. Clinical Trials of Nitrosoureas in Metastatic Sarcomas;346
25.1;I. Introduction;346
25.2;II. Materials and Method;347
25.3;III. Results;349
25.4;IV. Discussion;352
25.5;References;356
26;Chapter 28. High-Dose Nitrosourea (BCNU) and Autologous Bone Marrow Transplantation: A Phase I Study;358
26.1;I. Introduction;358
26.2;II. Materials and Methods;359
26.3;III. Results;359
26.4;IV. Discussion;361
26.5;References;362
27;Chapter 29. Amphotericin B: Interactions with Nitrosoureas and Other Antineoplastic Drugs;364
27.1;I. Introduction;364
27.2;II. Preclinical Studies;365
27.3;III. Clinical Studies;373
27.4;IV. Conclusions;379
27.5;References;380
28;Chapter 30. Activity of Nitrosoureas on Human Tumors In Vitro;382
28.1;I. Introduction;382
28.2;II. Materials and Methods;383
28.3;III. Results;384
28.4;IV. Discussion;385
28.5;References;386
29;Chapter 31. Streptozotocin;388
29.1;I. Introduction;388
29.2;II. Results;389
29.3;III. Conclusion;397
29.4;References;397
30;Chapter 32. Phase I and II Studies of PCNU;400
30.1;I. Introduction;400
30.2;II. Background;401
30.3;III. Phase I Trials of PCNU;402
30.4;IV. Clinical Responses;405
30.5;V. Pharmacological Information;405
30.6;VI. Conclusion;405
30.7;References;406
31;33. Chlorozotocin: Clinical Trials;408
31.1;I. Introduction;408
31.2;II. Phase I Trials;409
31.3;III. Clinical Pharmacology;409
31.4;IV. Phase II Trials;410
31.5;V. Conclusion;418
31.6;References;418
32;Chapter 34. Current Status of Nitrosoureas under Development in Japan;420
32.1;I. Introduction;420
32.2;II. ACNU;421
32.3;III. GANU;425
32.4;IV. MCNU;427
32.5;References;429
33;Chapter 35. Design of Clinical Trials with Nitrosourea;432
33.1;I. Introduction;432
33.2;II. Structure-Activity/Toxicity Relationships;433
33.3;III. Clinical Trials: Past, Present, and Future;433
33.4;IV. Future Clinical Trials;435
33.5;V. Conclusion;437
33.6;References;437