Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma

Cancer

Volumn 115, Issue 10, 2009, Pages 2188-2198

  Reardon, David A ^a   Egorin, Merrill J ^b,c   Desjardins, Annick ^a   Vredenburgh, James J ^a   Beumer, Jan H ^b,c   Lagattuta, Theodore F ^c   Gururangan, Sridharan ^a   Herndon II, James E ^a   Salvado, August J ^d   Friedman, Henry S ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

^d NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Hydroxyurea; Imatinib mesylate; Malignant glioma; Platelet derived growth factor; Vascular endothelial growth factor; Vatalanib

Indexed keywords

2 [2 METHYL 5 [4 (1 PIPERAZINYLMETHYL)BENZAMIDO]ANILINO] 4 (3 PYRIDYL)PYRIMIDINE; CARBAMAZEPINE; HYDROXYUREA; IMATINIB; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; PRIMIDONE; VATALANIB;

ADULT; AGED; AMINOTRANSFERASE BLOOD LEVEL; ANTIANGIOGENIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BLEEDING; BRAIN HEMORRHAGE; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CANCER RECURRENCE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE REGIMEN; DRUG TOLERABILITY; DRUG WITHDRAWAL; EDEMA; ENDOTHELIUM CELL; FATIGUE; FEMALE; GLIOBLASTOMA; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN TISSUE; HYPERTENSION; INFECTION; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MONOTHERAPY; MORNING DOSAGE; MUCOSA INFLAMMATION; NAUSEA; NEUTROPENIA; OUTCOME ASSESSMENT; PERICYTE; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; RECOMMENDED DRUG DOSE; SIDE EFFECT; THERAPY EFFECT; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; VASCULAR ENDOTHELIUM; VOMITING;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BRAIN NEOPLASMS; FEMALE; GLIOBLASTOMA; GLIOMA; HUMANS; HYDROXYUREA; MAGNETIC RESONANCE IMAGING; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PHTHALAZINES; PIPERAZINES; PYRIDINES; PYRIMIDINES; RECURRENCE; TREATMENT OUTCOME;

EID: 65649146868     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.24213     Document Type: Article

References (43)

1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987-996. (Pubitemid 40349501)
2. See SJ, Gilbert MR. Anaplastic astrocytoma: diagnosis, prognosis, and management. Semin Oncol. 2004;31:618-634.
3. Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a Pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007;11:83-95.
4. Vredenburgh JJ, Desjardins A, Herndon JE Jr, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007;25:4722-4729. (Pubitemid 350086473)
5. Vredenburgh JJ, Desjardins A, Herndon JE Jr, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13:1253-1259. (Pubitemid 46424067)
6. Cloughesy TF, Prados MD, Mikkelsen T, et al. A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM). Paper presented at: Proceedings of the American Society of Clinical Oncology, 2008; Chicago, Ill.
7. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 2000;60:2178-2189.
8. Carroll M, Ohno-Jones S, Tamura S, et al. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood. 1997;90:4947-4952.
9. Goldbrunner RH, Bendszus M, Wood J, et al. PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization. Neurosurgery. 2004;55:426-432; discussion 432.
10. Conrad C, Friedman HS, Reardon DA, et al. A Phase I/II trial of single-agent PTK 787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Paper presented at: Proceedings of the American Society of Clinical Oncology, 2004; New Orleans, La.
11. Reardon DA, Friedman HS, Yung WKA, et al. A phase I/II trial of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in combination with either temozolomide or lomustine for patients with recurrent glioblastoma multiforme (GBM). Paper presented at: Proceedings of the American Society of Clinical Oncology, 2004; New Orleans, La.
12. Thomas AL, Morgan B, Horsfield MA, et al. Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol. 2005;23:4162-4171.
13. Jones RL, Judson IR. The development and application of imatinib. Expert Opin Drug Saf. 2005;4:183-191.
14. Fleming TP, Saxena A, Clark WC, et al. Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res. 1992;52:4550-4553.
15. Hermanson M, Funa K, Hartman M, et al. Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res. 1992;52:3213-3219.
16. Lokker NA, Sullivan CM, Hollenbach SJ, Israel MA, Giese NA. Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Res. 2002;62:3729-3735.
17. Kilic T, Alberta JA, Zdunek PR, et al. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res. 2000;60:5143-5150. (Pubitemid 30336635)
18. Van Den Bent MJ, Brandes AA, van Oosterom A, et al. Multicentre phase II study of imatinib mesylate (Gleevec) in patients with recurrent glioblastoma: an EORTC NDDG/BTG intergroup study. Paper presented at: The 9th Annual Meeting of the Society for Neuro-Oncology; October 2004; Toronto, Canada.
19. Wen PY, Yung WK, Lamborn KR, et al. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res. 2006;12:4899-4907.
20. Desjardins A, Quinn JA, Vredenburgh JJ, et al. Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas. J Neurooncol. 2007;83:53-60. (Pubitemid 46647165)
21. Dresemann G. Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series. Ann Oncol. 2005;16:1702-1708. (Pubitemid 41510147)
22. Reardon DA, Egorin MJ, Quinn JA, et al. Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme. J Clin Oncol. 2005;23:9359-9368. (Pubitemid 46260195)
23. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003;111:1287-1295.
24. Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423.
25. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol. 1990;8:1277-1280.
26. Parise RA, Ramanathan RK, Hayes MJ, Egorin MJ. Liquid chromatographic-mass spectrometric assay for quantitation of imatinib and its main metabolite (CGP 74588) in plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;791:39-44.
27. Yeh KC, Kwan KC. A comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximation. J Pharmacokinet Biopharm. 1978;6:79-98.
28. Rocci ML Jr, Jusko WJ. LAGRAN program for area and moments in pharmacokinetic analysis. Comput Programs Biomed. 1983;16:203-216.
29. Yung WK, Prados MD, Yaya-Tur R, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999;17:2762-2771.
30. Yung WK, Albright RE, Olson J, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000;83:588-593. (Pubitemid 30636298)
31. Pope WB, Lai A, Nghiemphu P, Mischel P, Cloughesy TF. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology. 2006;66:1258-1260.
32. Chen W, Delaloye S, Silverman DH, et al. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol. 2007;25:4714-4721.
33. Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol. 2006;3:24-40.
34. Guo P, Hu B, Gu W, et al. Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment. Am J Pathol. 2003;162:1083-1093. (Pubitemid 36350654)
35. Abramsson A, Lindblom P, Betsholtz C. Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. J Clin Invest. 2003;112:1142-1151.
36. Yokoi K, Sasaki T, Bucana CD, et al. Simultaneous inhibition of EGFR, VEGFR, and platelet-derived growth factor receptor signaling combined with gemcitabine produces therapy of human pancreatic carcinoma and prolongs survival in an orthotopic nude mouse model. Cancer Res. 2005;65:10371-10380.
37. Griffin RJ, Williams BW, Wild R, et al. Simultaneous inhibition of the receptor kinase activity of vascular endothelial, fibroblast, and platelet-derived growth factors suppresses tumor growth and enhances tumor radiation response. Cancer Res. 2002;62:1702-1706.
38. Erber R, Thurnher A, Katsen AD, et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 2004;18:338-340.
39. Sonpavde G, Hutson TE, Sternberg CN. Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opin Investig Drugs. 2008;17:253-261.
40. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115-124. (Pubitemid 46089672)
41. Roboz GJ, Giles FJ, List AF, et al. Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. Leukemia. 2006;20:952-957.
42. Jost LM, Gschwind HP, Jalava T, et al. Metabolism and disposition of vatalanib (PTK787/ZK-222584) in cancer patients. Drug Metab Dispos. 2006;34:1817-1828.
43. Morgan B, Thomas AL, Drevs J, et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from 2 phase I studies. J Clin Oncol. 2003;21:3955-3964.