Phase I studies with the nonclassical antifolate nolatrexed dihydrochloride (AG337, THYMITAQ) administered orally for 5 days

Clinical Cancer Research

Volumn 5, Issue 1, 1999, Pages 111-118

  Hughes, Andy N ^a,b   Rafi, Imran ^a,b   Griffin, Melanie J ^a   Calvert, A Hilary ^a,b   Newell, David R ^a   Calvete, Joanne A ^a   Johnston, Amanda ^c   Clendeninn, Neil ^c   Boddy, Alan V ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b NEWCASTLE GENERAL HOSPITAL   (United Kingdom)

^c AGOURON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NOLATREXED;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER CHEMOTHERAPY; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL CANCER; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG FORMULATION; FEMALE; FOOD DRUG INTERACTION; GASTROINTESTINAL TOXICITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MALE; MAXIMUM PERMISSIBLE DOSE; NEUTROPENIA; ORAL DRUG ADMINISTRATION; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SOLID TUMOR; THROMBOCYTOPENIA;

ADMINISTRATION, ORAL; ADULT; AGED; ANTIMETABOLITES, ANTINEOPLASTIC; BIOLOGICAL AVAILABILITY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; FOOD-DRUG INTERACTIONS; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; NEOPLASMS; QUINAZOLINES;

EID: 0032902414     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (17)

1. Jackman, A. L., Calvert, A. H. Folate-based thymidylate synthase inhibitors as anti-cancer agents. Ann. Oncol., 6: 871-881, 1995.
2. Touroutoglou, N., and Pazdur, R. Thymidylate synthase inhibitors. Clin. Cancer Res., 2: 227-243, 1996.
3. Rustum, Y. M., Harstrick, A., Cao, S., Vanhoefer, U., Yin, M-B., Wilke, H., and Seeber, S. Thymidylate synthase inhibitors in cancer therapy: direct and indirect inhibitors. J. Clin. Oncol., 15: 389-400, 1997.
4. 10-propargyl-5,8-dideazafblic acid. Eur. J. Cancer & Clin. Oncol., 24: 201-204, 1988.
5. 10-propargyl-5,8-dideazafolic acid (CB3717) in advanced breast cancer. Eur. J. Cancer & Clin. Oncol., 24: 733-736, 1988.
6. Judson, I. R. Tomudex (raltitrexed) development: preclinical, Phase I and II studies. Anticancer Drugs, 8 (Suppl. 2): S5-S9, 1997.
7. Kerr, D. J. Clinical efficacy of tomudex (raltitrexed) in advanced colorectal cancer. Anticancer Drugs, 8 (Suppl. 2): S11-S15, 1997.
8. Webber, S. E., Bleckman, T. M., Attard, J., Deal, J. G., Kathardekar, V., Welsh, K. M., Webber, S., Janson, C. A., Matthews, D. A., Smith, W. W., Freer, S. T., Jordan, S. R., Bacquet, R. J., Howland, E. F., Booth, C. L. J., Ward, R. W., Hermann, S. M., White, J., Morse, C. A., Hilliard, J. A., and Bartlett, C. A. Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones. J. Med. Chem., 36: 733-746, 1993.
9. Rafi, I., Taylor, G. A., Calvete, J. A., Boddy, A. V., Balmanno, K., Bailey, N., Lind, M., Calvert, A. H., Webber, S., Jackson, R. C., Johnston, A., Clendeninn, N., and Newell, D. R. Clinical pharmacokinetic and pharmacodynamic studies with the nonclassical antifolate thymidylate synthase inhibitor 3,4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazolone dihydrochloride (AG337) given by 24-hour continuous intravenous infusion. Clin. Cancer Res., 1: 1275-1284, 1995.
10. Rafi, I., Boddy, A. V., Calvete, J. A., Taylor, G. A., Newell, D. R., Bailey, N. P., Lind, M. J., Green, M., Hines, J., Johnstone, A., Clendeninn, N., and Calvert, A. H. Preclinical, and Phase I clinical studies with the non-classical antifolate thymidylate synthase inhibitor nolatrexed dihydrochloride given by prolonged administration in patients with solid tumors. J. Clin. Oncol., 16: 1131-1141, 1998.
11. Loh, K. K., Cohn, A., Kelly, K., Glode, L. M., Stuart, K. E., Belani, C. P., Johnston, A., and Clendeninn, N. J. Phase II trials of THYMITAQ™ (AG337) in six solid tumour diseases. Proc. Am. Soc. Clin. Oncol., 15: 183, 1996.
12. th NCI-EORTC meeting, March 1996 (abstract 296).
13. Clendeninn, N. J., Collier, M. A., Johnston, A. L., Loh, K. K., Cohn, A., Kelly, K., Glode, L. M., Stuart, K. E., and Belan,i C. P. Thymitaq™ (AG337): a novel thymidylate synthase inhibitor with clinical activity in solid tumours. Proc. Am. Assoc. Cancer Res., 37: 171, 1996.
14. Stuart, K. E., Hajdenberg, J., Cohn, A., Loh, K. K., Miller, W., White, C., and Clendeninn, N. J. A Phase II trial of THYMITAQ™ (AG337) in patients with hepatocellular carcinoma. Proc. Am. Soc. Clin. Oncol., 15: 202, 1996.
15. Belani, C. P., Agarwala, S., Johnson, J., Cohn, A., Bernstein, J., Langer, C., Jones, V., White, C., Lob, K., Whiter, D., Chew, T., Johnston, A., and Clendeninn, N. A Phase II trial with Thymitaq™ (AG337) in patients with squamous cell carcinoma of the head and neck. Proc. Am. Soc. Clin. Oncol., 16: 387a, 1997.
16. Belani, C. P., Lembersky, B., Ramanathan, R., Cohn, A., Loh, K., Miller, W., Green, M., Chew, T., Johnston, A., and Clendeninn, N. A Phase II trial of Thymitaq™ (AG337) in patients with adenocarcinoma of the colon. Proc. Am. Soc. Clin. Oncol., 16: 272a, 1997.
17. Loh, K., Stuart, K., Cohn, A., White, C., Hines, J., Miller, W., Green, M. R., Chew, T., Johnston, A., and Clendeninn, N. A Phase II trial of Thymitaq™ (AG337) in patients with adenocarcinoma of the pancreas. Proc. Am. Soc. Clin. Oncol., 16: 265a, 1997.