Initial clinical trial and pharmacokinetics of Thymitaq(TM) (AG337) by 10-day continuous infusion in patients with advanced solid tumors

Cancer Chemotherapy and Pharmacology

Volumn 41, Issue 2, 1997, Pages 167-170

  Creaven, Patrick J ^a   Pendyala, Lakshmi ^a   Meropol, Neal J ^a   Clendeninn, Neil J ^b   Wu, Ellen Y ^b   Loewen, Gregory M ^a   Proefrock, April ^a   Johnston, Amanda ^b   Dixon, Mary ^b  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

^b AGOURON PHARMACEUTICALS INC   (United States)

Author keywords

10 Day infusion; Pharmacokinetics; Phase I; Thymitaq(TM)

Indexed keywords

FOLIC ACID ANTAGONIST; NOLATREXED;

ADULT; ADVANCED CANCER; AGED; ARTICLE; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL CANCER; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; HEAD AND NECK CARCINOMA; HUMAN; INFUSION PUMP; LUNG NON SMALL CELL CANCER; MAXIMUM ALLOWABLE CONCENTRATION; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; THROMBOSIS;

EID: 0031907650     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s002800050724     Document Type: Article

References (11)

1. Boddy AV, Calvete JA, Rafi I (1995) Non-linear pharmacokinetics in cancer patients of AG337, a rationally-designed thymidylate synthase (TS) inhibitor. Proc Am Assoc Cancer Res 36: 236
2. Clendeninn NJ, Johnston A (1996) Phase II trials of Thymitaq™ (AG337) in six solid tumor diseases. Ann Oncol 7(1): 86
3. Creaven PJ, Rustum YM, Petrelli NJ, Meropol NJ, Raghavan DR, Rodriguez-Bigas M, Levine EG, Frank C, Udvary-Nagy S, Proefrock A (1994) Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen. Cancer Chemother Pharmacol 34: 261
4. Loh KK, Cohn A, Kelly K, Glode LM, Stuart KE, Belani CP, Johnston A, Clendeninn NJ (1996) Phase II trials of Thymitaq™ (AG337) in six solid tumor diseases. Proc Am Soc Clin Oncol 15: 183
5. Rafi I, Taylor GA, Calvete JA, Balmanno K, Boddy AV, Bailey NB, Lind MJ, Newell D, Calvert AH (1995) A phase I clinical study of the novel antifolate AG337 given by a 5 day continuous infusion. Proc Am Assoc Cancer Res 36: 240
6. Rafi I, Taylor GA, Calvete JA, Boddy AV, Balmanno K, Bailey N, Lind M, Calvert AH, Webber S, Jackson RC, Johnston A, Clendeninn N, Newell DR (1995) Clinical pharmacokinetic and pharmacodynamic studies with the nonclassical antifolate thymidylate synthase inhibitor 3,4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazoline-dihydrochloride (AG337) given by 24-hour continuous intravenous infusion. Clin Cancer Res 1: 1275
7. Rafi I, Boddy AV, Taylor GA, Calvete JA, Griffin M, Calvert AH, Lind M, Bailey N, Johnston A, Clendeninn N, Newell DR (1996) Pharmacokinetic (PK) and pharmacodynamic (PD) studies of the non-classical thymidylate synthase (TS) inhibitor AG337 given as a 5 day iv infusion. Proc Am Assoc Cancer Res 37: 177
8. Rocci ML Jr, Jusko WJ (1983) LAGRAN program for area and moments in pharmacokinetic analysis. Comput Programs Biomed 16: 203
9. Soni N, Meropol NJ, Pendyala L, Noel D, Schacter LP, Gunton KE, Creaven PJ (1997) Phase I and pharmacokinetic study of etoposide phosphate by protracted venous infusion. J Clin Oncol 15: 766
10. Stuart KE, Hajdenberg J, Cohn A, Loh KK, Miller W, White C, Clendeninn NJ (1996) A phase II trial of Thymitaq™ (AG337) in patients with hepatocellular carcinoma (HCC). Proc Am Soc Clin Oncol 15: 202
11. Webber S, Bartlett CA, Boritzki TJ, Hilliard JA, Howland EF, Johnston AL, Kosa M, Margosiak SA, Morse CA, Shetty BV (1996) AG337, a novel lipophilic thymidylate synthase inhibitor: in vitro and in vivo preclinical studies. Cancer Chemother Pharmacol 37: 509