A phase I and pharmacokinetic study of LY231514, the multitargeted antifolate

Clinical Cancer Research

Volumn 4, Issue 3, 1998, Pages 605-610

  McDonald, Alexander C ^a,d   Vasey, Paul A ^a   Adams, Lynne ^a   Walling, Jacqueline ^b   Woodworth, James R ^b   Abrahams, Trent ^b   McCarthy, Sean ^b   Bailey, Nigel P ^c   Siddiqui, Neelam ^c   Lind, Michael J ^c   Calvert, A Hilary ^c   Twelves, Christopher J ^a   Cassidy, James ^a   Kaye, Stanley B ^a  

^a BEATSON WEST OF SCOTLAND CANCER CENTRE   (United Kingdom)

^b ELI LILLY AND COMPANY   (United States)

^c NEWCASTLE GENERAL HOSPITAL   (United Kingdom)

^d CLATTERBRIDGE CENTRE FOR ONCOLOGY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FOLIC ACID ANTAGONIST; PEMETREXED;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; DIARRHEA; DRUG BLOOD LEVEL; DRUG CLEARANCE; FATIGUE; FEMALE; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; LIVER TOXICITY; MALE; MUCOSA INFLAMMATION; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RASH; SOLID TUMOR;

ADULT; AGED; ANTINEOPLASTIC AGENTS; CREATININE; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GLUTAMATES; GUANINE; HUMANS; LEUKOCYTE COUNT; LIVER FUNCTION TESTS; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; NEOPLASMS; NEUTROPENIA; PLATELET COUNT; REGRESSION ANALYSIS;

EID: 15644372742     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (12)

1. Taylor, E. C., and Kuhnt, D. A dideazotetrahydrofolate analogue lacking a chiral centre at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrollo[2,3-d]pyrimidin-5-yl)ethyl]- benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase. J. Med. Chem., 35: 4450-4454, 1992.
2. Shih, C., Chen, V. J., Gossett, L. S., Gates, S., MacKellar, W., Habeck, L. L., Shackelford, K. A., Mendelsohn, L., Soose, D., Patel, V. F., Andis, S., Bewley, J. R., Rayl, E. A., Moroson, B. A., Beardsley, G. P., Kohler, W., Ratnam, M., and Schultz, R. LY231514, a pyrollo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res., 57: 1116-1123, 1997.
3. Rinaldi, D. A., Burris, H. A., Dorr, F. A., Woodworth, J. R., Kuhn, J. G., Eckardt, J. R., Rodriguez, G., Corso, S. W., Fields, S. M., Langley, C., Clark, G., Faries, D., Lu, P., and von Hoff, D. D. Initial Phase I evaluation of the novel thymidylate synthase inhibitor LY231514, using the modified continual reassessment method for dose escalation. J. Clin. Oncol., 13: 2842-2850, 1995.
4. Lokich, J. J., Ahlgren, J. D., Gullo, J. J., Philips, J. A., and Fryer, J. G. A prospective randomised comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program study. J. Clin. Oncol., 7: 425-432, 1989.
5. Rinaldi, D. A., Burris, H. A., Dorr, F. A., Rodriguez, G., Eckardt, J. R., Fields, S. M., Woodworth, J. R., Kuhn, J. G., Langley, C., Clark, G., Lu, P., and von Hoff, D. D. A Phase I evaluation of LY231514, a novel multi-targeted antifolate administered every 21 days. Proc. Am. Soc. Clin. Oncol. Annu. Meet., 15: 1559, 1996.
6. Jackman, A. L., and Calvert, A. H. Folate-based thymidylate synthase inhibitors as anti-cancer drugs. Ann. Oncol., 6: 871-881, 1995.
7. Shargel, L., and Yu, A. Applied Biopharmaceutics and Pharmacokinetics, p. 441. Norwalk, CT: Appleton & Lange, 1993.
8. Machover, D., Goldschmidt, E., Chollet, P., Metzger, G., Zittoun, J., Marquet, J., Vandenbulcke, J. M., Misset, J. L., Schwarzenberg, L., Fourtillan, J. B., Gaget, H., and Mathe, G. Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high dose folinic acid. J. Clin. Oncol., 4: 685-696, 1986.
9. Peters, G. J., van der Wilt, C. L., van Triest, B., Codacci-Pisanelli, G., Johnston, P. G., van Groeningen, C. J., and Pinedo, H. Thymidylate synthase and drug resistance. Eur. J. Cancer, 31A: 1299-1305, 1995.
10. Swain, S. M., Lipmann, M. E., Egan, E. F., Drake, J. C., Steinberg, S. M., and Allegra, C. J. Fluorouracil and high dose leucovorin in previously treated patients with metastatic breast cancer. J. Clin. Oncol., 7: 890-899, 1989.
11. Johnston, P. G., Fisher, E. R., Rockette, H. E., Fisher, B., Wolmark, N., Drake, J. C., Chabner, B. A., and Allegra, C. J. The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer. J. Clin. Oncol., 12: 2640-2647, 1994.
12. Touroutoglou, N., and Pazdur, R. Thymidylate synthase inhibitors. Clin. Cancer Res., 2: 227-243, 1996.