Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: A phase II study

Clinical Cancer Research

Volumn 19, Issue 6, 2013, Pages 1557-1566

  Zhu, Andrew X ^a,c   Ancukiewicz, Marek ^a,c   Supko, Jeffrey G ^a,c   Sahani, Dushyant V ^a,c   Blaszkowsky, Lawrence S ^a,c   Meyerhardt, Jeffrey A ^b,c   Abrams, Thomas A ^b,c   McCleary, Nadine Jackson ^b,c   Bhargava, Pankaj ^b,c   Muzikansky, Alona ^a   Sheehan, Susan ^a   Regan, Eileen ^b   Vasudev, Eamala ^a   Knowles, Michelle ^a   Fuchs, Charles S ^b,c   Ryan, David P ^a,c   Jain, Rakesh K ^a,c   Duda, Dan G ^a,c,d  

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPOIETIN 2; CARBON ANHYDRASE 9; CARBONATE DEHYDRATASE; CD133 ANTIGEN; CD34 ANTIGEN; CD45 ANTIGEN; CEDIRANIB; FIBROBLAST GROWTH FACTOR 2; GAMMA INTERFERON; GROWTH FACTOR; INTERLEUKIN 6; INTERLEUKIN 8; PLACENTAL GROWTH FACTOR; SCATTER FACTOR; SOMATOMEDIN C; STROMAL CELL DERIVED GROWTH 1ALPHA; TRANSFORMING GROWTH FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BONE MARROW SUPPRESSION; CANCER PATIENT; CANCER STEM CELL; CLINICAL ARTICLE; CONFUSION; COUGHING; DEHYDRATION; DESQUAMATION; DIARRHEA; DISEASE MARKER; DRUG EFFICACY; DRUG ERUPTION; DRUG RESPONSE; DRUG SAFETY; DYSPHONIA; EPISTAXIS; FATIGUE; FEMALE; FEVER; HAND FOOT SYNDROME; HEADACHE; HEART MUSCLE ISCHEMIA; HEMATEMESIS; HUMAN; HYPERBILIRUBINEMIA; HYPERCALCEMIA; HYPERKALEMIA; HYPERTENSION; HYPOCALCEMIA; HYPOGLYCEMIA; HYPOKALEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; HYPOTHYROIDISM; LEUKOPENIA; LIVER CELL CARCINOMA; LIVER FUNCTION; LUNG EMBOLISM; LYMPHOCYTOPENIA; MALE; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN BLOOD LEVEL; PROTEINURIA; SIDE EFFECT; STOMATITIS; TASTE DISORDER; THROMBOCYTOPENIA; VOMITING; WEIGHT REDUCTION;

AGED; CARCINOMA, HEPATOCELLULAR; DISEASE-FREE SURVIVAL; DRUG TOXICITY; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LIVER NEOPLASMS; MALE; MIDDLE AGED; NEOPLASM PROTEINS; NEOPLASM STAGING; PROTEIN KINASE INHIBITORS; QUINAZOLINES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1;

EID: 84875181434     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-12-3041     Document Type: Article

References (29)

1. Zhu AX, Duda DG, Sahani DV, Jain RK. HCC and angiogenesis: possible targets and future directions. Nat Rev Clin Oncol 2011;8: 292-301.
2. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90.
3. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2008;10:25-34.
4. de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 2006; 6:24-37.
5. Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 2008;8: 618-31.
6. De Palma M, Venneri MA, Roca C, Naldini L. Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med 2003;9:789-95.
7. Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 2007;25:911-20.
8. Suzuki K, Hayashi N, Miyamoto Y, Yamamoto M, Ohkawa K, Ito Y, et al. Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res 1996;56: 3004-9.
9. Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM, et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst 2006;98:326-34.
10. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64: 7099-109.
11. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 2005;65: 4389-400.
12. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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 2000;92: 205-16.
13. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52-60.
14. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008;100:698-711.
15. Batchelor TT, Duda DG, di Tomaso E, Ancukiewicz M, Plotkin SR, Gerstner E, et al. Phase II study of cediranib, an oral pan-VEGF receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 2010;28:2817-23.
16. Genovese T, Mazzon E, Crisafulli C, Di Paola R, Muia C, Bramanti P, et al. False discovery control with p-value weighting. Biometrika 2006:509-24.
17. Drevs J, Siegert P, Medinger M, Mross K, Strecker R, Zirrgiebel U, et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 2007;25:3045-54.
18. Alberts SR, Fitch TR, Kim GP, Morlan BW, Dakhil SR, Gross HM, et al. Cediranib (AZD2171) in patients with advanced hepatocellular carcinoma: a phase II north central cancer treatment group clinical trial. Am J Clin Oncol 2012;35: 329-33.
19. Ramalingam SS, Belani CP, Mack PC, Vokes EE, Longmate J, Govindan R, et al. Phase II study of Cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). J Thorac Oncol 2010;5:1279-84.
20. Faivre S, Raymond E, Boucher E, Douillard J, Lim HY, Kim JS, et al. Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study. Lancet Oncol 2009;10:794-800.
21. Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 2009;27:3027-35.
22. Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009;6:327-38.
23. Duda DG, Willett CG, Ancukiewicz M, di Tomaso E, Shah M, Czito BG, et al. Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer. Oncologist 2010;15: 577-83.
24. Gerstner ER, Emblem KE, Chi AS, Eichler AF, Hochberg F, Drappatz J, et al. Effects of cediranib, a VEGF signaling inhibitor, in combination with chemoradiation on tumor blood flow and survival in newly diagnosed glioblastoma. J Clin Oncol 2012;30:(suppl; abstr 2009).
25. Meyerhardt JA, Ancukiewicz M, Abrams TA, Schrag D, Enzinger PC, Chan JA, et al. Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474) as therapy for patients with previously treated metastastic colorectal cancer. PLoS One 2012;7:e38231.
26. Tolaney SM, Duda DG, Boucher Y, Goel S, Martin J, Ancukiewicz M, et al. A phase II study of preoperative (preop) bevacizumab (bev) followed by dose-dense (dd) doxorubicin (A)/cyclophosphamide (C)/ paclitaxel (T) in combination with bev in HER2-negative operable breast cancer (BC). J Clin Oncol 2012;30:(suppl; abstr 1026).
27. Zhu AX, Duda DG, Ancukiewicz M, di Tomaso E, Clark JW, Miksad R, et al. Exploratory analysis of early toxicity of sunitinib in advanced hepatocellular carcinoma patients: kinetics and potential biomarker value. Clin Cancer Res 2011;17:918-27.
28. Rolny C, Mazzone M, Tugues S, Laoui D, Johansson I, Coulon C, et al. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell 2011;19:31-44.
29. Tam BY, Wei K, Rudge JS, Hoffman J, Holash J, Park SK, et al. VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis. Nat Med 2006;12:793-800.