Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors

BMC Cancer

Volumn 17, Issue 1, 2017, Pages

  Négrier, Sylvie ^a   Pérol, David ^b   Bahleda, Rastislav ^c   Hollebecque, Antoine ^c   Chatelut, Etienne ^d   Boyle, Helen ^b   Cassier, Philippe ^b   Metzger, Séverine ^b   Blanc, Ellen ^b   Soria, Jean Charles ^c   Escudier, Bernard ^c  

^a UNIVERSITÉ DE LYON   (France)

^b CENTRE LÉON BÉRARD   (France)

^c INSTITUT GUSTAVE ROUSSY   (France)

^d CANCER RESEARCH CENTER OF TOULOUSE   (France)

Author keywords

Bevacizumab; Combination Angiogenesis; Pazopanib; Phase I trial; Renal carcinoma

Indexed keywords

ASPARTATE AMINOTRANSFERASE; BEVACIZUMAB; MONOCLONAL ANTIBODY KI 67; PAZOPANIB; PROTEIN TYROSINE KINASE INHIBITOR; SUNITINIB; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; ANTINEOPLASTIC AGENT; PYRIMIDINE DERIVATIVE; SULFONAMIDE;

ABDOMINAL PAIN; ADULT; ADVANCED CANCER; ANOREXIA; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASTHENIA; BACKACHE; CANCER COMBINATION CHEMOTHERAPY; CLINICAL ARTICLE; COHORT ANALYSIS; CONFUSION; DIARRHEA; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; DRY SKIN; DYSGEUSIA; DYSPHONIA; DYSPNEA; EPISTAXIS; FATIGUE; FEASIBILITY STUDY; FEMALE; HAND FOOT SYNDROME; HEADACHE; HEMORRHOID; HUMAN; HYPERBILIRUBINEMIA; HYPERNATREMIA; HYPERTENSION; HYPOTHYROIDISM; KIDNEY CARCINOMA; KIDNEY METASTASIS; MALE; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; MUSCLE CONTRACTURE; MUSCULOSKELETAL PAIN; MYALGIA; NAUSEA; NECK PAIN; NEUTROPENIA; PARESTHESIA; PERIANAL ABSCESS; PHASE 1 CLINICAL TRIAL; POSTOPERATIVE HEMORRHAGE; PROTEINURIA; PYELONEPHRITIS; SEIZURE; STOMATITIS; THORACIC MUSCULOSKELETAL PAIN; THORAX PAIN; THORAXIC MUSCULOSKELETAL PAIN; THROMBOCYTOPENIA; THROMBOTIC THROMBOCYTOPENIC PURPURA; URINARY TRACT INFECTION; VEIN THROMBOSIS; VOMITING; AGED; CLINICAL TRIAL; DRUG MONITORING; KIDNEY TUMOR; MIDDLE AGED; MORTALITY; MULTIMODALITY CANCER THERAPY; PATHOLOGY; RENAL CELL CARCINOMA; TREATMENT OUTCOME;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BEVACIZUMAB; CARCINOMA, RENAL CELL; COMBINED MODALITY THERAPY; DRUG MONITORING; FEMALE; HUMANS; KIDNEY NEOPLASMS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PYRIMIDINES; SULFONAMIDES; TREATMENT OUTCOME;

EID: 85027509965     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/s12885-017-3527-7     Document Type: Article

References (46)

1. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427-34.
2. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-42.
3. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542-50.
4. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666-76.
5. 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.
6. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115-24.
7. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103-11.
8. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28:1061-8.
9. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-81.
10. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125-34.
11. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378:1931-9.
12. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:917-27.
13. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16:1473-82.
14. Azad NS, Posadas EM, Kwitkowski VE, Steinberg SM, Jain L, Annunziata CM, et al. Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol. 2008;26:3709-14.
15. Negrier S, Gravis G, Perol D, Chevreau C, Delva R, Bay JO, et al. Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial. Lancet Oncol. 2011;12:673-80.
16. Castellano D, Capdevila J, Sastre J, Alonso V, Llanos M, Garcia-Carbonero R, et al. Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumour: a phase II study of Spanish Neuroendocrine tumour group (GETNE0801). Eur J Cancer. 2013;49:3780-7.
17. Mina LA, Yu M, Johnson C, Burkhardt C, Miller KD, Zon R. A phase II study of combined VEGF inhibitor (bevacizumab+sorafenib) in patients with metastatic breast cancer: Hoosier oncology group study BRE06-109. Investig New Drugs. 2013;31:1307-10.
18. Mahalingam D, Malik L, Beeram M, Rodon J, Sankhala K, Mita A, et al. Phase II study evaluating the efficacy, safety, and pharmacodynamic correlative study of dual antiangiogenic inhibition using bevacizumab in combination with sorafenib in patients with advanced malignant melanoma. Cancer Chemother Pharmacol. 2014;74:77-84.
19. Galanis E, Anderson SK, Lafky JM, Uhm JH, Giannini C, Kumar SK, et al. Phase II study of bevacizumab in combination with sorafenib in recurrent glioblastoma (N0776): a north central cancer treatment group trial. Clin Cancer Res. 2013;19:4816-23.
20. Buti S, Bersanelli M. Combination therapy in kidney cancer: the next revolution? Lancet Oncol. 2015;16:1441-2.
21. Hegde PS, Jubb AM, Chen D, Li NF, Meng YG, Bernaards C, et al. Predictive impact of circulating vascular endothelial growth factor in four phase III trials evaluating bevacizumab. Clin Cancer Res. 2013;19:929-37.
22. Ljungberg B, Jacobsen J, Haggstrom-Rudolfssson S, Rasmuson T, Lindh G, Grankvist K. Tumour vascular endothelial growth factor (VEGF) mRNA in relation to serum VEGF protein levels and tumour progression in human renal cell carcinoma. Urol Res. 2003;31:335-40.
23. Negrier S, Perol D, Menetrier-Caux C, Escudier B, Pallardy M, Ravaud A, et al. Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6--from the Groupe Francais d'Immunotherapie. J Clin Oncol. 2004;22:2371-8.
24. Choueiri TK, Motzer RJ. Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med. 2017;376:354-66.
25. Feldman DR, Baum MS, Ginsberg MS, Hassoun H, Flombaum CD, Velasco S, et al. Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:1432-9.
26. Rini BI, Garcia JA, Cooney MM, Elson P, Tyler A, Beatty K, et al. A phase I study of sunitinib plus bevacizumab in advanced solid tumors. Clin Cancer Res. 2009;15:6277-83.
27. Moreno G. V, Basu B, Molife LR, Kaye SB: combining antiangiogenics to overcome resistance: rationale and clinical experience. Clin Cancer Res. 2012;18:3750-61.
28. Mittal K, Koon H, Elson P, Triozzi P, Dowlati A, Chen H, et al. Dual VEGF/VEGFR inhibition in advanced solid malignancies: clinical effects and pharmacodynamic biomarkers. Cancer Biol Ther. 2014;15:975-81.
29. Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010;28:475-80.
30. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26:5422-8.
31. Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, et al. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007;25:4536-41.
32. Flaherty KT, Manola JB, Pins M, McDermott DF, Atkins MB, Dutcher JJ, et al. BEST: a randomized phase II study of vascular endothelial growth factor, RAF Kinase, and mammalian target of Rapamycin combination targeted therapy with Bevacizumab, Sorafenib, and Temsirolimus in advanced renal cell carcinoma--a trial of the ECOG-ACRIN cancer research group (E2804). J Clin Oncol. 2015;33:2384-91.
33. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004;22:2184-91.
34. Socinski MA, Scappaticci FA, Samant M, Kolb MM, Kozloff MF. Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer. J Thorac Oncol. 2010;5:354-60.
35. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-47.
36. Imbs DC, Negrier S, Cassier P, Hollebecque A, Varga A, Blanc E, et al. Pharmacokinetics of pazopanib administered in combination with bevacizumab. Cancer Chemother Pharmacol. 2014;73:1189-96.
37. Hurwitz HI, Dowlati A, Saini S, Savage S, Suttle AB, Gibson DM, et al. Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res. 2009;15:4220-7.
38. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369:722-31.
39. Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES study. J Clin Oncol. 2014;32:1412-8.
40. van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379:1879-86.
41. Kapadia S, Hapani S, Choueiri TK, Wu S. Risk of liver toxicity with the angiogenesis inhibitor pazopanib in cancer patients. Acta Oncol. 2013;52:1202-12.
42. Frangie C, Lefaucheur C, Medioni J, Jacquot C, Hill GS, Nochy D. Renal thrombotic microangiopathy caused by anti-VEGF-antibody treatment for metastatic renal-cell carcinoma. Lancet Oncol. 2007;8:177-8.
43. Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358:1129-36.
44. Kapiteijn E, Brand A, Kroep J, Gelderblom H. Sunitinib induced hypertension, thrombotic microangiopathy and reversible posterior leukencephalopathy syndrome. Ann Oncol. 2007;18:1745-7.
45. Bruce JY, Kolesar JM, Hammers H, Stein MN, Carmichael L, Eickhoff J, et al. A phase I pharmacodynamic trial of sequential sunitinib with bevacizumab in patients with renal cell carcinoma and other advanced solid malignancies. Cancer Chemother Pharmacol. 2014;73:485-93.
46. Tewari KS, Sill MW, Long HJ III, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370:734-43.