Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA- alkyltransferase: Phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors

Clinical Cancer Research

Volumn 12, Issue 5, 2006, Pages 1577-1584

  Ranson, Malcolm ^a   Middleton, Mark R ^a,f   Bridgewater, John ^c   Lee, Siow Ming ^c   Dawson, Martin ^b   Jowle, Debra ^a   Halbert, Gavin ^d   Waller, Sue ^b   McGrath, Helen ^b   Gumbrell, Lindsey ^b   McElhinney, R Stanley ^e   Donnelly, Dorothy ^e   McMurry, T Brian H ^e   Margison, Geoffrey P ^b  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF STRATHCLYDE   (United Kingdom)

^e TRINITY COLLEGE DUBLIN   (Ireland)

^f CHURCHILL HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

6 O ALKYLGUANINE DNA ALKYLTRANSFERASE INHIBITOR; LOMEGUATRIB; TEMOZOLOMIDE; UNCLASSIFIED DRUG;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BONE MARROW SUPPRESSION; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL CANCER; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG SAFETY; ENZYME ACTIVITY; ENZYME INACTIVATION; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPERGLYCEMIA; HYPOALBUMINEMIA; HYPOCALCEMIA; HYPONATREMIA; INJECTION SITE BURNING; KIDNEY TUMOR; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MALE; MAXIMUM TOLERATED DOSE; MELANOMA; NAUSEA; NEUTROPENIA; OVARY TUMOR; PERIPHERAL BLOOD MONONUCLEAR CELL; PERITONEUM TUMOR; PHARMACODYNAMICS; PHARYNGITIS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEINURIA; SOLID TUMOR; STOMATITIS; THROMBOCYTOPENIA; TUMOR BIOPSY; VOMITING;

ADENOSINE TRIPHOSPHATASES; ADOLESCENT; ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DACARBAZINE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FEMALE; GUANINE; HUMANS; MALE; MIDDLE AGED; NEOPLASM METASTASIS; NEOPLASMS; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE; SAFETY;

EID: 33645085569     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-05-2198     Document Type: Article

References (31)

1. Middleton MR, Margison GP. Improvement of chemotherapy efficiency by inactivation of a DNA-repair pathway. Lancet Oncol 2003;4:37-44.
2. Gerson SL. Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol 2002;20:2388-99.
3. 6-Alkylguanine-DNA alkyltransferase inactivation in cancer chemotherapy. Mini Rev Med Chem 2003;3:471-85.
4. 6-alkylguanine-DNA transferases. Mutat Res 1990;233:165-75.
5. Margison GP, O'Connor PJ. Biological consequences of reactions with DNA: role of specific lesions. In: Cooper CS, Graver PL, editors. Handbook of experimental pharmacology. Berlin: Springer-Verlag: 1990. p. 547-71.
6. 6-Methylguanine-DNA methyltransferase activity in human tumors. Carcinogenesis 1992;13:1503-7.
7. 6-Methylguanine-DNA methyltransferase in human normal and tumor tissue from brain, lung and ovary. Cancer Res 1991;51:4131-4.
8. 6-Alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine. Cancer Res 1991;51:619-23.
9. 6-benzylguanine/temozolomide combination: an evaluation in a human melanoma xenograft model. Cancer Chemother Pharmacol 1997;40:266-72.
10. Micetich K, Futscher B, Koch D, et al. Phase I study of streptozotocin and carmustine sequenced administration in patients with advanced cancer. J Natl Cancer Inst 1992;84:256-60.
11. Lee SM, Margison GP, Woodcock AA, et al. Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma. Br J Cancer 1993;67:1356-60.
12. 6-alkylguanine-DNA alkyltransferase. Clin Cancer Res 1996;2:1129-34.
13. Clemons M, Ranson M, Margison JM, et al. Pharmacokinetic, biochemical and clinical effects of dimethyltriazenoimidazole-4-carboxamide-bischloroethyl nitrosourea combination therapy in patients with advanced breast cancer. Int J Cancer 2003;103:686-92.
14. 6- benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents. Proc Natl Acad Sci U S A 1990;87:5368-72.
15. 6-Benzylguanine-mediated enhancement of chemotherapy. Mol Cancer Ther 2002;1:943-8.
16. 6-(4-bromothenyl)guanine on different temozolomide schedules in a human melanoma xenograft model. Int J Cancer 2002;100:615-7.
17. 6-benzyl- 2′-deoxyguanosine. Clin Cancer Res 2003;9:1-7.
18. 6-Benzylguanine and its role in chemotherapy. Clin Cancer Res 1997;3:837-47.
19. 6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol 2000;18:3522-8.
20. 6-benzylguanine followed by carmustine in patients with advanced cancer. Clin Cancer Res 2000;6:3025-31.
21. 6-benzylguanine in patients with surgically resectable tumors. Clin Cancer Res 2002;8:19-23.
22. 6-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma. J Clin Oncol 2002;20:2277-83.
23. 6-(4-Bromothenyl) guanine improves the therapeutic index of temozolomide against A375M melanoma xenografts. Int J Cancer 2000;85:248-52.
24. NCI. Guidelines for reporting of adverse drug reactions. Bethesda (MD): National Cancer Institute; 1998.
25. World Health Organization. The WHO handbook for reporting results of cancer treatment. WHO publication number 48. Geneva: WHO; 1979.
26. 6-Alkylguanine-DNA alkyltransferase assay. Methods Mol Biol 2000;152:49-61.
27. Danson S, Lorigan P, Arance A, et al. Randomized phase II study of temozolomide given every 8 hours or daily with either interferon α-2b or thalidomide in metastatic malignant melanoma. J Clin Oncol 2003;21:2551-7.
28. van den Bent MJ, Taphoorn MJ, Brandes AA, et al. Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the EORTC Brain Tumor Group Study 26971. J Clin Oncol 2003;21:2525-8.
29. 6-Methylguanine formation, repair protein depletion and clinical outcome with a 4 hr schedule of temozolomide in the treatment of advanced melanoma: results of a phase II trial. Int J Cancer 2000;88:469-73.
30. 6-alkylguanine-DNA-alkyltransferase. Clin Cancer Res 2001;7:2309-17.
31. 6-Benzylguanine: a clinical trial establishing the biochemical modulatory dose in tumor tissue for alkyltransferase-directed DNA repair. Cancer Res 1999;59:2402-10.