Anti-tumour and anti-vascular effects of cediranib (AZD2171) alone and in combination with other anti-tumour therapies

Cancer Chemotherapy and Pharmacology

Volumn 71, Issue 4, 2013, Pages 1021-1032

  Kendrew, Jane ^a   Odedra, Rajesh ^a   Logié, Armelle ^a   Taylor, Paula J ^a   Pearsall, Sharon ^a   Ogilvie, Donald J ^a,b   Wedge, Stephen R ^a,c   Jürgensmeier, Juliane M ^a  

^a ASTRAZENECA   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Angiogenesis; AZD2171; Cancer; Cediranib; Combination drug therapy; Tumour

Indexed keywords

BEVACIZUMAB; CEDIRANIB; CISPLATIN; DOCETAXEL; FLUOROURACIL; GEFITINIB; GEMCITABINE; IMATINIB; IRINOTECAN; N ACETYLCOLCHINOL PHOSPHATE; OXALIPLATIN; PEMETREXED; SARACATINIB; SELUMETINIB; ANTINEOPLASTIC AGENT; QUINAZOLINE DERIVATIVE; VASCULOTROPIN RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CANCER REGRESSION; COLORECTAL CANCER; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG TOLERABILITY; FEMALE; LUNG CANCER; MONOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR VOLUME; TUMOR XENOGRAFT; VULVA CANCER; ANIMAL; DRUG ANTAGONISM; DRUG SCREENING; HUMAN; NEOVASCULARIZATION (PATHOLOGY);

ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; HUMANS; MICE; NEOVASCULARIZATION, PATHOLOGIC; QUINAZOLINES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

MLCS; MLOWN;

EID: 84878854334     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-013-2097-x     Document Type: Article

References (51)

1. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, Chester R, Jackson JA, Boffey SJ, Kilburn LL, Barnett S, Richmond GH, Wadsworth PF, Walker M, Bigley AL, Taylor ST, Cooper L, Beck S, Jürgensmeier JM, Ogilvie DJ (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 65:4389-4400 (Pubitemid 40775678)
2. Heckman CA, Holopainen T, Wirzenius M, Keskitalo S, Jeltsch M, Yla-Herttuala S, Wedge SR, Jürgensmeier JM, Alitalo K (2008) The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis. Cancer Res 68:4754-4762
3. Maris JM, Courtright J, Houghton PJ, Morton CL, Gorlick R, Kolb EA, Lock R, Tajbakhsh M, Reynolds CP, Keir ST, Wu J, Smith MA (2008) Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program. Pediatr Blood Cancer 50:581-587 (Pubitemid 351155829)
4. Goodlad RA, Ryan AJ, Wedge SR, Pyrah IT, Alferez D, Poulsom R, Smith NR, Mandir N, Watkins AJ, Wilkinson RW (2006) Inhibiting vascular endothelial growth factor receptor-2 signaling reduces tumor burden in the ApcMin/+ mouse model of early intestinal cancer. Carcinogenesis 27:2133-2139 (Pubitemid 44530588)
5. Miller KD, Miller M, Mehrotra S, Agarwal B, Mock BH, Zheng QH, Badve S, Hutchins GD, Sledge GW Jr (2006) A physiologic imaging pilot study of breast cancer treated with AZD2171. Clin Cancer Res 12:281-288 (Pubitemid 43166205)
6. Drevs J, Siegert P, Medinger M, Mross K, Strecker R, Zirrgiebel U, Harder J, Blum H, Robertson J, Jürgensmeier JM, Puchalski TA, Young H, Saunders O, Unger C (2007) Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 25:3045-3054 (Pubitemid 47218051)
7. Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83-95 (Pubitemid 46075199)
8. Fiedler W, Mesters R, Heuser M, Ehninger G, Berdel WE, Zirrgiebel U, Robertson JD, Puchalski TA, Collins B, Jurgensmeier JM, Serve H (2010) An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid leukemia. Leuk Res 34:196-202
9. Matulonis UA, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C, Berkenblit A, Campos S, Horowitz N, Cannistra SA, Lee H, Lee J, Roche M, Hill M, Whalen C, Sullivan L, Tran C, Humphreys BD, Penson RT (2009) Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 27:5601-5606
10. Mulders P, Hawkins R, Nathan P, de Jong I, Osanto S, Porfiri E, Protheroe A, van Herpen CM, Mookerjee B, Pike L, Jürgensmeier JM, Gore ME (2012) Cediranib monotherapy in patients with advanced renal cell carcinoma: results of a randomised Phase II study. Eur J Cancer 48:527-537
11. van Cruijsen H, Voest EE, Punt CJ, Hoekman K, Witteveen PO, Meijerink MR, Puchalski TA, Robertson J, Saunders O, Jürgensmeier JM, van Herpen CM, Giaccone G (2010) Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours. Eur J Cancer 46:901-911
12. Trarbach T, Schultheis B, Gauler TC, Schneider V, Strumberg D, Eberhardt WE, Le Scouiller S, Marotti M, Brown KH, Drevs J (2012) Phase I open-label study of cediranib, an oral inhibitor of VEGF signalling, in combination with the oral Src inhibitor saracatinib in patients with advanced solid tumours. Invest New Drugs 30:1962-1971
13. LoRusso P, Shields AF, Gadgeel S, Vaishampayan U, Guthrie T, Puchalski T, Xu J, Liu Q (2011) Cediranib in combination with various anticancer regimens: results of a Phase I multi-cohort study. Invest New Drugs 29:1395-1405
14. Laurie SA, Gauthier I, Arnold A, Shepherd FA, Ellis PM, Chen E, Goss G, Powers J, Walsh W, Tu D, Robertson J, Puchalski TA, Seymour L (2008) Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. J Clin Oncol 26:1871-1878
15. Chen E, Jonker D, Gauthier I, Maclean M, Wells J, Powers J, Seymour L (2009) Phase I study of cediranib in combination with oxaliplatin and infusional 5-fluorouracil in patients with advanced colorectal cancer. Clin Cancer Res 15:1481-1486
16. Goss G, Shepherd FA, Laurie S, Gauthier I, Leighl N, Chen E, Feld R, Powers J, Seymour L (2009) A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. Eur J Cancer 45:782-788
17. Jonker D, Cripps C, Gauthier I, Maroun J, Moore M, Matthews S, Seymour L (2006) Phase I study of AZD2171 in combination with capecitabine (CAPE) in patients with advanced colorectal cancer (CRC). Ann Oncol 17(Suppl 9):ix122 (abst 355P)
18. Satoh T, Yamaguchi K, Boku N, Okamoto W, Shimamura T, Yamazaki K, Shi X, Mishima H (2012) Phase I results from a two-part Phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer. Invest New Drugs 30:1511-1518
19. Hoff PM, Hochhaus A, Pestalozzi BC, Tebbutt NC, Li J, Kim TW, Koynov KD, Kurteva G, Pintér T, Cheng Y, van Eyll B, Pike L, Fielding A, Robertson JD, Saunders MP, On behalf of the HORIZON II study group (2012) Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, Phase III study (HORIZON II). J Clin Oncol 30:3596-3603
20. Schmoll H-J, Cunningham D, Sobrero A, Karapetis CS, Rougier P, Koski SL, Kocakova I, Bondarenko I, Bodoky G, Mainwaring P, Salazar R, Barker P, Mookerjee B, Robertson J, Van Cutsem E, On behalf of the HORIZON III study group (2012) Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized Phase III study (HORIZON III). J Clin Oncol 30:3588-3595
21. Batchelor TT, Duda DG, di Tomaso E, Ancukiewicz M, Plotkin SR, Gerstner E, Eichler AF, Drappatz J, Hochberg FH, Benner T, Louis DN, Cohen KS, Chea H, Exarhopoulos A, Loeffler JS, Moses MA, Ivy P, Sorensen AG, Wen PY, Jain RK (2010) Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 28:2817-2823
22. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427-434 (Pubitemid 36910021)
23. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115-124 (Pubitemid 46089672)
24. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125-134 (Pubitemid 46089673)
25. Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte O, Motzer RJ, Bycott P, Liau KF, Freddo J, Trask PC, Kim S, Rini BI (2007) Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol 8:975-984 (Pubitemid 47629888)
26. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarba JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061-1068
27. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542-2550 (Pubitemid 44917502)
28. 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 350:2335-2342 (Pubitemid 38702844)
29. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB III (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539-1544 (Pubitemid 46733080)
30. Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, Boffey SJ, Valentine PJ, Curwen JO, Musgrove HL, Graham GA, Hughes GD, Thomas AP, Stokes ES, Curry B, Richmond GH, Wadsworth PF, Bigley AL, Hennequin LF (2002) ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 62:4645-4655
31. Merlino GT, Xu YH, Ishii S, Clark AJ, Semba K, Toyoshima K, Yamamoto T, Pastan I (1984) Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. Science 224:417-419 (Pubitemid 14134005)
32. Strawn LM, Mann E, Elliger SS, Chu LM, Germain LL, Niederfellner G, Ullrich A, Shawver LK (1994) Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor. J Biol Chem 269:21215-21222 (Pubitemid 24266496)
33. Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 8:579-591
34. Azad NS, Posadas EM, Kwitkowski VE, Steinberg SM, Jain L, Annunziata CM, Minasian L, Sarosy G, Kotz HL, Premkumar A, Cao L, McNally D, Chow C, Chen HX, Wright JJ, Figg WD, Kohn EC (2008) Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol 26:3709-3714
35. Goss GD, Arnold A, Shepherd FA, Dediu M, Ciuleanu TE, Fenton D, Zukin M, Walde D, Laberge F, Vincent MD, Ellis PM, Laurie SA, Ding K, Frymire E, Gauthier I, Leighl NB, Ho C, Noble J, Lee CW, Seymour L (2010) Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J Clin Oncol 28:49-55
36. Hong DS, Davis D, Naing A, Fu S, Falchook G, Ricks LW, Bekele N, Mittleman D, Liu W, Ivy P, Herbst R, Kurzrock R (2009) Phase I clinical trial evaluating the safety, pharmacokinetics and biological effect of intravenous bevacizumab (avastin) in combination with escalating doses of AZD2171 (cediranib) administered orally for 21 consecutive days to patients with advanced malignancies (NCI protocol #7534). Mol Cancer Ther 8(12 Suppl 1):abst A4
37. Sharma S, Abhyankar V, Burgess RE, Infante J, Trowbridge RC, Tarazi J, Kim S, Tortorici M, Chen Y, Robles RL (2010) A phase I study of axitinib (AG-013736) in combination with bevacizumab plus chemotherapy or chemotherapy alone in patients with metastatic colorectal cancer and other solid tumors. Ann Oncol 21:297-304
38. Feldman DR, Baum MS, Ginsberg MS, Hassoun H, Flombaum CD, Velasco S, Fischer P, Ronnen E, Ishill N, Patil S, Motzer RJ (2009) Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 27:1432-1439
39. Garrido-Laguna I, Kurzrock R, Wheler J, Falchook GS, Piha-Paul SA, Naing FA, Hinojosa C, Mistry R, Scamardo A, Culotta KS, Ekmekcioglu S, Wen S, Camacho LH, Ivy SP, Hong DS (2011) Dual inhibition of VEGF pathway: phase I trial of bevacizumab and cediranib in advanced solid tumors. J Clin Oncol 29(15S):abst 3065
40. Siemann DW, Shi W (2004) Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors. Int J Radiat Oncol Biol Phys 60:1233-1240 (Pubitemid 39440810)
41. Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, Blumenschein G Jr, Lee JJ, Liu DD, Truong MT, Hong WK, Tran H, Tsao A, Xie D, Ramies DA, Mass R, Seshagiri S, Eberhard DA, Kelley SK, Sandler A (2005) Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol 23:2544-2555
42. Tabernero J (2007) The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res 5:203-220 (Pubitemid 46569773)
43. Wakeling AE, Guy SP, Woodburn JR, Ashton SE, Curry BJ, Barker AJ, Gibson KH (2002) ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 62:5749-5754 (Pubitemid 35204731)
44. Bozec A, Formento P, Lassalle S, Lippens C, Hofman P, Milano G (2007) Dual inhibition of EGFR and VEGFR pathways in combination with irradiation: antitumour supra-additive effects on human head and neck cancer xenografts. Br J Cancer 97:65-72 (Pubitemid 47012080)
45. Naumov GN, Nilsson MB, Cascone T, Briggs A, Straume O, Akslen LA, Lifshits E, Byers LA, Xu L, Wu HK, Janne P, Kobayashi S, Halmos B, Tenen D, Tang XM, Engelman J, Yeap B, Folkman J, Johnson BE, Heymach JV (2009) Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res 15:3484-3494
46. Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J (2011) Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet 377:1846-1854
47. Takahashi O, Komaki R, Smith PD, Jürgensmeier JM, Ryan A, Bekele BN, Wistuba II, Jacoby JJ, Korshunova MV, Biernacka A, Erez B, Hosho K, Herbst RS, O'Reilly MS (2012) Combined MEK and VEGFR inhibition in orthotopic human lung cancer models results in enhanced inhibition of tumor angiogenesis, growth, and metastasis. Clin Cancer Res 18:1641-1654
48. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58-62 (Pubitemid 40093472)
49. van der Veldt AA, Lubberink M, Bahce I, Walraven M, de Boer MP, Greuter HN, Hendrikse NH, Eriksson J, Windhorst AD, Postmus PE, Verheul HM, Serne EH, Lammertsma AA, Smit EF (2012) Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs. Cancer Cell 21:82-91
50. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013-2019
51. Morton CL, Maris JM, Keir ST, Gorlick R, Kolb EA, Billups CA, Wu J, Smith MA, Houghton PJ (2012) Combination testing of cediranib (AZD2171) against childhood cancer models by the pediatric preclinical testing program. Pediatr Blood Cancer 58:566-571