Phase i study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients

Cancer Chemotherapy and Pharmacology

Volumn 69, Issue 6, 2012, Pages 1507-1518

  Reardon, David A ^a   Conrad, Charles A ^b   Cloughesy, Timothy ^c   Prados, Michael D ^d   Friedman, Henry S ^e   Aldape, Kenneth D ^b   Mischel, Paul ^c   Xia, Jane ^f   DiLea, Clivord ^f   Huang, Jerry ^f   Mietlowski, William ^f   Dugan, Margaret ^f   Chen, Wei ^c   Yung, W K Alfred ^b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e DUKE CANCER INSTITUTE   (United States)

^f NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Epidermal growth factor receptor; Glioblastoma; RAD001; Tyrosine kinase inhibitor; Vascular endothelial growth factor receptor

Indexed keywords

6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ANTICONVULSIVE AGENT; ANTIDIARRHEAL AGENT; ANTINEOPLASTIC AGENT; AQM 674; DRUG METABOLITE; EPIDERMAL GROWTH FACTOR RECEPTOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER RADIOTHERAPY; CONFUSION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG COMPETITION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG ELIMINATION; DRUG ERUPTION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG TUMOR LEVEL; DRUG WITHDRAWAL; FEMALE; GLIOBLASTOMA; HEART ATRIUM FIBRILLATION; HEMIPARESIS; HUMAN; HUMAN TISSUE; INSOMNIA; LIVER DYSFUNCTION; LIVER TOXICITY; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MULTIPLE DRUG DOSE; MUSCLE WEAKNESS; NAUSEA; NEUROSURGERY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEINURIA; RECOMMENDED DRUG DOSE; RECURRENT CANCER; SEIZURE; SIDE EFFECT; SINGLE DRUG DOSE; STEADY STATE; STOMATITIS; THERAPY RESISTANCE; TIME TO MAXIMUM PLASMA CONCENTRATION; URINARY TRACT INFECTION; VOMITING;

ADULT; AGED; BRAIN NEOPLASMS; FEMALE; GLIOBLASTOMA; HUMANS; MALE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; PROTEIN KINASE INHIBITORS; PURINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; TUMOR MARKERS, BIOLOGICAL;

EID: 84863796631     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-012-1854-6     Document Type: Article

References (45)

1. Stupp R, Mason WP, van den Bent MJ, for the European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987-996
2. Krex D, Klink B, Hartmann C, for the German Glioma Network et al (2007) Long-term survival with glioblastoma multiforme. Brain 130:2596-2606
3. Vredenburgh JJ, Desjardins A, Herndon JE 2nd et al (2007) Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 13:1253-1259
4. Vredenburgh JJ, Desjardins A, Herndon JE 2nd et al (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722-4729
5. Desjardins A, Reardon DA, Herndon JE 2nd et al (2008) Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res 14:7068-7073
6. Friedman HS, Prados MD, Wen PY et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733-4740
7. Kreisl TN, Kim L, Moore K et al (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740-745
8. Batchelor TT, Sorensen AG, di Tomaso E et al (2007) AZD2171, a Pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83-95
9. Avastin [package insert] (2009) Genentech, Inc, South San Francisco, CA
10. Maher EA, Brennan C, Wen PY et al (2006) Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. Cancer Res 66:11502-11513
11. Bredel M, Scholtens DM, Harsh GR et al (2009) A network model of a cooperative genetic landscape in brain tumors. J Amer Med Assoc 302:261-275
12. Parsons DW, Jones D, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807-1812
13. Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061-1068
14. Libermann TA, Nusbaum HR, Razon N et al (1985) Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313:144-147
15. Steck PA, Gallick GE, Maxwell SA et al (1986) Expression of epidermal growth factor receptor and associated glycoprotein on cultured human brain tumor cells. J Cell Biochem 32:1-10
16. Humphrey PA, Wong AJ, Vogelstein B et al (1988) Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts. Cancer Res 48:2231-2238
17. Frederick L, Wang XY, Eley G, James CD (2000) Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 60:1383-1387
18. Nishikawa R, Ji XD, Harmon RC et al (1994) A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci USA 91:7727-7731
19. Nagane M, Coufal F, Lin H, Bögler O, Cavenee WK, Huang HJ (1996) A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res 56:5079-5086
20. van den Bent MJ, Brandes AA, Rampling R et al (2009) Randomized phase II trial oferlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27:1268-1274
21. Franceschi E, Cavallo G, Lonardi S et al (2007) Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Br J Cancer 96:1047-1051
22. Rich JN, Reardon DA, Peery T et al (2004) Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 22:133-142
23. Goudar RK, Shi Q, Hjelmeland MD et al (2005) Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition. Mol Cancer Ther 4:101-112
24. Traxler P, Allegrini PR, Brandt R et al (2004) AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 64:4931-4941
25. Reardon D, Cloughesy T, Conrad C et al (2005) A phase I study of AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, in recurrent GBM patients. J Clin Oncol 23:16s (suppl; abstr 3063)
26. Simon R, Freidlin B, Rubinstein L et al (1997) Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89:1138-1147
27. Martinelli E, Takimoto CH, van Oosterom AT et al (2005) AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases: preliminary phase 1 results. J Clin Oncol 23:201s (suppl; abstr 3039)
28. Xiong HQ, Takimoto C, Rojo F et al (2007) A phase I study of AEE788, a multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, to determine safety, PK and PD in patients (pts) with advanced colorectal cancer (CRC) and liver metastases. J Clin Oncol 25:179s (suppl; abstr 4065)
29. Shuster J (2002) Optimal two-stage designs for single arm phase II cancer trials. J Biopharm Stat 12:39-51
30. Dent S, Zee B, Dancey J et al (2001) Application of a new multinomial phase II stopping rule using response and early progression. J Clin Oncol 19:785-791
31. Simmons ML, Lamborn KR, Takahashi M et al (2001) Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients. Cancer Res 61:1122-1128
32. Macdonald DR, Cascino TL, Schold SC Jr et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277-1280
33. Aldape K, Cloughesy T, Reardon D et al (2005) Analyses of EGF and VEGF signaling pathways in recurrent glioblastoma patients in a Phase I study of single agent AEE788. In: Presented at the proceedings of the AACR-NCI-EORTC international conference on "Molecular Targets and Cancer Therapeutics," November 14-18, 2005, Philadelphia, PA
34. Younes MN, Park YW, Yazici YD et al (2006) Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol Cancer Ther 5:2696-2705
35. Wu W, Onn A, Isobe T et al (2007) Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade. Mol Cancer Ther 6:471-483
36. Ciardiello F, Caputo R, Damiano V et al (2003) Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. Clin Cancer Res 9:1546-1556
37. Yokoi K, Thaker PH, Yazici S et al (2005) Dual inhibition of epidermal growth factor receptor and vascular endothelial growth factor receptor phosphorylation by AEE788 reduces growth and metastasis of human colon carcinoma in an orthotopic nude mouse model. Cancer Res 65:3716-3725
38. Sasaki T, Kitadai Y, Nakamura T et al (2007) Inhibition of epidermal growth factor receptor and vascular endothelial growth factor receptor phosphorylation on tumor-associated endothelial cells leads to treatment of orthotopic human colon cancer in nude mice. Neoplasia 9:1066-1077
39. Petrelli A, Giordano S (2008) From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. Curr Med Chem 15:422-432
40. Prados M, Gilbert M, Kuhn J, Lamborn K, Cloughesy T, Lieberman F, Puduvalli V, Robins HI, Lassman A, Wen PY (2009) Phase I/II study of sorefenib and erlotinib for patients with recurrent glioblastoma (GBM) (NABTC 05-02). J Clin Oncol 27:88s (suppl; abstr 2005)
41. Wen PY, Cloughesy T, Kuhn J, Lamborn K, Abrey LE, Lieberman F, Robins HI, Wright J, Prados MD, Gilbert M (2009) Phase I/II study of sorafenib and temsirolimus for patients with recurrent glioblastoma (GBM) (NABTC 05-02). J Clin Oncol 27:88s (suppl; abstr 2006)
42. Chang SM, Kuhn J, Lamborn K et al (2009) Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04-02). J Clin Oncol 27:88s (suppl; abstr 2004)
43. Schmidinger M, Zielinski CC, Vogl UM et al (2008) Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 26:5204-5212
44. Torino F, Corsello SM, Longo R et al (2009) Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nat Rev Clin Oncol 6:219-228
45. Gutierrez ME, Kummar S, Giaccone G (2009) Next generation oncology drug development: opportunities and challenges. Nat Rev Clin Oncol 6:259-265