Mass balance, excretion and metabolism of [ 14C] ASA404 in cancer patients in a phase i trial

Cancer Chemotherapy and Pharmacology

Volumn 69, Issue 5, 2012, Pages 1145-1154

  McKeage, M J ^a   Fong, P C ^a   Hong, X ^b   Flarakos, J ^b   Mangold, J ^b   Du, Y ^b   Tanaka, C ^b   Schran, H ^b  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Antivascular; Excretion; Metabolism; Radiolabel study

Indexed keywords

6 METHYLHYDROXYVADIMEZAN; 6 METHYLHYDROXYVADIMEZAN ACYL GLUCURONIDE; CARBON 14; CARBOPLATIN; DIMER; DOCETAXEL; DRUG METABOLITE; GLUCURONIDE; MITOMYCIN C; NITROSOUREA DERIVATIVE; PACLITAXEL; UNCLASSIFIED DRUG; VADIMEZAN; VADIMEZAN ACYL GLUCURONIDE; 5,6 DIMETHYLXANTHENONEACETIC ACID; 5,6-DIMETHYLXANTHENONEACETIC ACID; ANTINEOPLASTIC AGENT; CARBON; XANTHONE DERIVATIVE;

ADULT; ADVANCED CANCER; AGED; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CANCER PATIENT; CLINICAL ARTICLE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG EXCRETION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG URINE LEVEL; FECES ANALYSIS; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN TISSUE; ISOTOPE LABELING; LIQUID SCINTILLATION COUNTING; MALE; MASS BALANCE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; MULTIPLE CYCLE TREATMENT; OPEN STUDY; PHARMACOLOGICAL PARAMETERS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RADIOACTIVITY; SINGLE DRUG DOSE; SOLID TUMOR; TIME TO MAXIMUM PLASMA CONCENTRATION; URINALYSIS; CLINICAL TRIAL; INTRAVENOUS DRUG ADMINISTRATION; METHODOLOGY; MIDDLE AGED; NEOPLASM; PATHOLOGY; PROTEIN BINDING; TIME;

AGED; ANTINEOPLASTIC AGENTS; CARBON RADIOISOTOPES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FEMALE; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MASS SPECTROMETRY; MIDDLE AGED; NEOPLASMS; PROTEIN BINDING; TIME FACTORS; XANTHONES;

EID: 84862303483     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-011-1809-3     Document Type: Article

References (17)

1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74-108 (Pubitemid 40372904)
2. McKeage MJ, Baguley BC (2010) Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer. Cancer 116(8):1859-1871. doi:10.1002/cncr.24975
3. Baguley BC (2003) Antivascular therapy of cancer: DMXAA. Lancet Oncol 4(3):141-148. doi:S1470204503010180 (Pubitemid 36322304)
4. Jameson MB, Thompson PI, Baguley BC, Evans BD, Harvey VJ, Porter DJ, McCrystal MR, Small M, Bellenger K, Gumbrell L, Halbert GW, Kestell P (2003) Clinical aspects of a phase I trial of 5, 6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Br J Cancer 88(12):1844-1850. doi:10.1038/sj.bjc.6600992 (Pubitemid 36829657)
5. Rustin GJ, Bradley C, Galbraith S, Stratford M, Loadman P, Waller S, Bellenger K, Gumbrell L, Folkes L, Halbert G (2003) 5, 6-dimethylxanthenone-4- acetic acid (DMXAA), a novel antivascular agent: phase I clinical and pharmacokinetic study. Br J Cancer 88(8):1160-1167. doi:10.1038/sj.bjc.6600885 (Pubitemid 36606327)
6. McKeage MJ, Fong P, JeVery M, Baguley BC, Kestell P, Ravic M, Jameson MB (2006) 5, 6-Dimethylxanthenone-4-acetic acid in the treatment of refractory tumors: a phase I safety study of a vascular disrupting agent. Clin Cancer Res 12(6):1776-1784. doi:10.1158/1078-0432.CCR-05-1939
7. McKeage MJ, Reck M, Jameson MB, Rosenthal MA, Gibbs D, Mainwaring PN, Freitag L, Sullivan R, Von Pawel J (2009) Phase II study of ASA404 (vadimezan, 5, 6-dimethylxanthenone-4-acetic acid/DMXAA) 1800 mg/m(2) combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Lung Cancer 65:192-197. doi:10.1016/j.lungcan.2009.03.027
8. McKeage MJ, Von Pawel J, Reck M, Jameson MB, Rosenthal MA, Sullivan R, Gibbs D, Mainwaring PN, Serke M, LaWtte JJ, Chouaid C, Freitag L, Quoix E (2008) Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Br J Cancer 99(12):2006-2012. doi:10.1038/sj.bjc.6604808
9. Pili R, Rosenthal MA, Mainwaring PN, Van Hazel G, Srinivas S, Dreicer R, Goel S, Leach J, Wong S, Clingan P (2010) Phase II study on the addition of ASA404 (vadimezan; 5, 6-dimethylxanthenone-4-acetic acid) to docetaxel in CRMPC. Clin Cancer Res 16(10):2906-2914. doi:10.1158/1078-0432.CCR-09-3026
10. Lara PN Jr, Douillard JY, Nakagawa K, von Pawel J, McKeage MJ, Albert I, Losonczy G, Reck M, Heo DS, Fan X, Fandi A, Scagliotti G (2011) Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol 29(22):2965-2971. doi:10.1200/JCO.2011.35.0660
11. Zhou S, Kestell P, Paxton JW (2002) 6-methylhydroxylation of the anti-cancer agent 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) by Xavin-containing monooxygenase 3. Eur J Drug Metab Pharmacokinet 27(3):179-183
12. Zhou SF, Paxton JW, Tingle MD, Kestell P (2000) IdentiWcation of the human liver cytochrome P450 isoenzyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5, 6-dimethylxanthenone-4-acetic acid. Drug Metab Dispos 28(12):1449-1456
13. Miners JO, Valente L, Lillywhite KJ, Mackenzie PI, Burchell B, Baguley BC, Kestell P (1997) Preclinical prediction of factors inXuencing the elimination of 5, 6-dimethylxanthenone-4-acetic acid, a new anticancer drug. Cancer Res 57(2):284-289 (Pubitemid 27036607)
14. Zhou SF, Paxton JW, Tingle MD, Kestell P, Jameson MB, Thompson PI, Baguley BC (2001) IdentiWcation and reactivity of the major metabolite (beta-1-glucuronide) of the anti-tumour agent 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) in humans. Xenobiotica 31(5):277-293. doi:10.1080/00498250110043544 (Pubitemid 32643308)
15. Jameson MB, Baguley BC, Kestell P, Zhao L, Paxton JW, Thompson PI, Waller S (2007) Pharmacokinetics of 5, 6-dimethylxanthenone-4-acetic acid (AS1404), a novel vascular disrupting agent, in phase I clinical trial. Cancer Chemother Pharmacol 59(5):681-687. doi:10.1007/s00280-006-0322-6 (Pubitemid 46295132)
16. Li J, Jameson MB, Baguley BC, Pili R, Baker SD (2008) Population pharmacokinetic-pharmacodynamic model of the vasculardisrupting agent 5, 6-dimethylxanthenone-4-acetic acid in cancer patients. Clin Cancer Res 14(7):2102-2110. doi:10.1158/1078-0432.CCR-07-1475 (Pubitemid 351551122)
17. Zhou SF, Kestell P, Paxton JW (2002) 6-Methylhydroxylation of the anti-cancer agent 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) by Xavin-containing monooxygenase 3. Eur J Drug Metab Pharmacokinet 27(3):179-183