Phase I, pharmacokinetic and pharmacodynamic evaluation of CYT997, an orally-bioavailable cytotoxic and vascular-disrupting agent

Investigational New Drugs

Volumn 31, Issue 1, 2013, Pages 126-135

  Burge, Matthew ^a   Francesconi, Alessandra B ^a   Kotasek, Dusan ^b   Fida, Rosa ^c   Smith, Gregg ^c   Wilks, Andrew ^c   Vasey, Paul A ^d   Lickliter, Jason D ^e  

^a ROYAL BRISBANE AND WOMEN'S HOSPITAL   (Australia)

^b Adelaide Cancer Centre   (Australia)

^c Cytopia Ltd   (Australia)

^d WESLEY HOSPITAL   (Australia)

^e MONASH MEDICAL CENTRE   (Australia)

Author keywords

Dynamic contrast enhanced magnetic resonance imaging; Oral CYT997; Pharmacokinetics; Phase I clinical trial; Vascular disrupting agent

Indexed keywords

GADOLINIUM PENTETATE MEGLUMINE; LEXIBULIN; VASCULAR TARGETING AGENT; VON WILLEBRAND FACTOR;

ABDOMINAL DISTENSION; ADRENAL CORTEX CARCINOMA; ADULT; ADVANCED CANCER; AGED; ANEMIA; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; ASCITES; BREAST CANCER; CHEMOTHERAPY INDUCED EMESIS; CLINICAL ARTICLE; COLORECTAL CANCER; CONSTIPATION; CONTRAST ENHANCEMENT; DEHYDRATION; DRUG BIOAVAILABILITY; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG INTERMITTENT THERAPY; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; HUMAN; HYPERTENSION; HYPOXIA; INFECTION; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NUCLEAR MAGNETIC RESONANCE IMAGING; PANCREAS ADENOCARCINOMA; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PORTAL VEIN THROMBOSIS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; QT PROLONGATION; SIDE EFFECT; SINUS TACHYCARDIA; SOLID TUMOR; SWEATING; THYMOMA; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; AGED; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; CYTOTOXINS; FEMALE; HUMANS; MALE; MIDDLE AGED; NEOPLASMS; PYRIDINES; PYRIMIDINES; TUBULIN MODULATORS;

EID: 84873093943     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-012-9813-y     Document Type: Article

References (19)

1. Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29(6 Suppl 16):15-18
2. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335-2342
3. Lindsay CR, MacPherson IR, Cassidy J (2009) Current status of cediranib: the rapid development of a novel anti-angiogenic therapy. Future Oncol 5(4):421-432
4. Stevenson JP, Rosen M, Sun W, Gallagher M, Haller DG, Vaughn D, Giantonio B, Zimmer R, Petros WP, Stratford M, Chaplin D, Young SL, Schnall M, O'Dwyer PJ (2003) Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow. J Clin Oncol 21(23):4428-4438
5. Hinnen P, Eskens FA (2007) Vascular disrupting agents in clinical development. Br J Cancer 96(8):1159-1165
6. Mooney CJ, Nagaiah G, Fu P, Wasman JK, Cooney MM, Savvides PS, Bokar JA, Dowlati A, Wang D, Agarwala SS, Flick SM, Hartman PH, Ortiz JD, Lavertu PN, Remick SC (2009) A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid 19(3):233-240
7. Traynor AM, Gordon MS, Alberti D, Mendelson DS, Munsey MS, Wilding G, Gammans RE, Read WL (2010) A dose escalation, safety, and tolerability study of MN-029 in patients with advanced solid tumors. Invest New Drugs 28(4):509-515
8. Burns CJ, Fantino E, Phillips ID, Su S, Harte MF, Bukczynska PE, Frazzetto M, Joffe M, Kruszelnicki I, Wang B, Wang Y, Wilson N, Dilley RJ, Wan SS, Charman SA, Shackleford DM, Fida R, Malcontenti-Wilson C, Wilks AF (2009) CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo. Mol Cancer Ther 8(11):3036-3045
9. Burns CJ, Fantino E, Powell AK, Shnyder SD, Cooper PA, Nelson S, Christophi C, Malcontenti-Wilson C, Dubljevic V, Harte MF, Joffe M, Phillips ID, Segal D, Wilks AF, Smith GD (2011) The microtubule depolymerizing agent CYT997 causes extensive ablation of tumor vasculature in vivo. J Pharmacol Exp Ther 339(3):799-806
10. Lickliter JD, Francesconi AB, Smith G, Burge M, Coulthard A, Rose S, Griffin M, Milne R, McCarron J, Yeadon T, Wilks A, Cubitt A, Wyld DK, Vasey PA (2010) Phase I trial of CYT997, a novel cytotoxic and vascular-disrupting agent. Br J Cancer 103(5):597-606
11. Lee KW, Lip GY, Tayebjee M, Foster W, Blann AD (2005) Circulating endothelial cells, von Willebrand factor, interleukin-6, and prognosis in patients with acute coronary syndromes. Blood 105(2):526-532
12. Cytopia (2009) CYT997 investigator's brochure, 7th edn. Richmond, Victoria
13. Powell AK, Shnyder SD, Cooper PA, Nelson S, Burns CJ, Fida R, Smith GD (2009) Antitumor activity of CYT997: a phase II vascular disrupting agent administered orally in combination with cisplatin in a colon adenocarcinoma xenograft model. Mol Cancer Ther 8(12 Suppl):A16
14. Simon R, Freidlin B, Rubinstein L, Arbuck SG, Collins J, Christian MC (1997) Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89(15):1138-1147
15. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205-216
16. Ceelen W, Smeets P, Backes W, Van Damme N, Boterberg T, Demetter P, Bouckenooghe I, De Visschere M, Peeters M, Pattyn P (2006) Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model. Int J Radiat Oncol Biol Phys 64(4):1188-1196
17. Rischin D, Bibby DC, Chong G, Kremmidiotis G, Leske AF, Matthews CA, Wong SS, Rosen MA, Desai J (2011) Clinical, pharmacodynamic, and pharmacokinetic evaluation of BNC105P: a phase I trial of a novel vascular disrupting agent and inhibitor of cancer cell proliferation. Clin Cancer Res 17(15):5152-5160
18. McKeage MJ, Fong P, Jeffery 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
19. LoRusso PM, Gadgeel SM, Wozniak A, Barge AJ, Jones HK, DelProposto ZS, DeLuca PA, Evelhoch JL, Boerner SA, Wheeler C (2008) Phase I clinical evaluation of ZD6126, a novel vascular-targeting agent, in patients with solid tumors. Invest New Drugs 26(2):159-167