A Phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors

Clinical Cancer Research

Volumn 20, Issue 8, 2014, Pages 2192-2204

  Angevin, Eric ^a   Tabernero, Josep ^d   Elez, Elena ^d   Cohen, Steven J ^f   Bahleda, Rastilav ^a   Van Laethem, Jean Luc ⁱ   Ottensmeier, Christian ^l   Lopez Martin, Jose A ^e   Clive, Sally ^m   Joly, Florence ^b   Ray Coquard, Isabelle ^c   Dirix, Luc ^k   Machiels, Jean Pascal ^j   Steven, Neil ⁿ   Reddy, Manjula ^g   Hall, Brett ^o   Puchalski, Thomas A ^g   Bandekar, Rajesh ^g   Van De Velde, Helgi ^g   Tromp, Brenda ^o   Vermeulen, Jessica ^o   Kurzrock, Razelle ^h   more..

^a INSTITUT GUSTAVE ROUSSY   (France)

^b CHU CÔTE DE NACRE   (France)

^c CENTRE LÉON BÉRARD   (France)

^d HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^e HOSPITAL UNIVERSITARIO 12 DE OCTUBRE   (Spain)

^f FOX CHASE CANCER CENTER   (United States)

^g JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^h UNIVERSITY OF TEXAS   (United States)

ⁱ ERASME HOSPITAL   (Belgium)

^j CLINIQUES UNIVERSITAIRES SAINT LUC   (Belgium)

^k SINT AUGUSTINUS HOSPITAL   (Belgium)

^l UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST   (United Kingdom)

^m WESTERN GENERAL HOSPITAL   (United Kingdom)

ⁿ UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST   (United Kingdom)

^o Janssen Research and Development   (Netherlands)

more..

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 6; KRAS PROTEIN, HUMAN; MONOCLONAL ANTIBODY; ONCOPROTEIN; RAS PROTEIN; SILTUXIMAB;

ADULT; AGED; ANIMAL; AREA UNDER THE CURVE; CHEMICALLY INDUCED; CHO CELL LINE; CLINICAL TRIAL; CRICETULUS; DOSE RESPONSE; DRUG EFFECTS; FATIGUE; FEMALE; GENETICS; HAMSTER; HUMAN; IMMUNOLOGY; LIVER; MALE; METABOLIC CLEARANCE RATE; METABOLISM; MIDDLE AGED; MUTATION; NAUSEA; NEOPLASMS; NEUTROPENIA; PATHOPHYSIOLOGY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; TREATMENT OUTCOME;

ADULT; AGED; ANIMALS; ANTIBODIES, MONOCLONAL; AREA UNDER CURVE; CHO CELLS; CRICETINAE; CRICETULUS; DOSE-RESPONSE RELATIONSHIP, DRUG; FATIGUE; FEMALE; HUMANS; INTERLEUKIN-6; LIVER; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; MUTATION; NAUSEA; NEOPLASMS; NEUTROPENIA; PROTO-ONCOGENE PROTEINS; RAS PROTEINS; TREATMENT OUTCOME;

EID: 84898967209     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-2200     Document Type: Article

References (31)

1. Trikha M, Corringham R, Klein B, Rossi JF. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 2003;9:4653-65.
2. van Zaanen HCT, Lokhorst HM, Aarden LA, Rensink HJ, Warnaar SO, van der Lelie J, et al. Chimaeric anti-interleukin 6 monoclonal antibodies in the treatment of advanced multiple myeloma: a phase I doseescalating study. Br J Haematol 1998;102:783-90.
3. Van Zaanen HCT, Lokhorst HM, Aarden LA, Rensink HJ, Warnaar SO, Van Oers MH. Blocking interleukin-6 activity with chimeric anti-IL6 monoclonal antibodies in multiple myeloma: effects on soluble IL6 receptor and soluble gp130. Leuk Lymphoma 1998;31:551-8.
4. Blay JY, Negrier S, Combaret V, Attali S, Goillot E, Merrouche Y, et al. Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. Cancer Res 1992;52:3317-22.
5. Michalaki V, Syrigos K, Charles P, Waxman J. Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer 2004;90: 2312-6.
6. Benoy I, Salgado R, Colpaert C, Weytjens R, Vermeulen PB, Dirix LY. Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. Clin Breast Cancer 2002;2:311-5.
7. Kurebayashi J. Regulation of interleukin-6 secretion from breast cancer cells and its clinical implications. Breast Cancer 2000;7:124-9.
8. Ebrahimi B, Tucker SL, Li D, Abbruzzese JL, Kurzrock R. Cytokines in pancreatic carcinoma: correlation with phenotypic characteristics and prognosis. Cancer 2004;101:2727-36.
9. Scambia G, Testa U, Benedetti Panici P, Foti E, Martucci R, Gadducci A, et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer 1995;71:354-6.
10. Syed V, Ulinski G, Mok SC, Ho SM. Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells. J Natl Cancer Inst 2002;94:617-29.
11. Fang X, Yu S, Bast RC, Liu S, Xu HJ, Hu SX, et al. Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J Biol Chem 2004;279:9653-61.
12. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-Kras genes. Cell 1988;53:549-54.
13. Bos JL. ras oncogenes in human cancer: a review. Cancer Res 1989; 49:4682-9.
14. Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008;26:374-9.
15. Raponi M, Winkler H, Dracopoli NC. KRAS mutations predict response to EGFR inhibitors. Curr Opin Pharmacol 2008;8:413-8.
16. Ancrile B, Lim KH, Counter CM. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 2007;21:1714-9.
17. Young B, Zaritsky J. Hepcidin for clinicians. Clin J Am Soc Nephrol 2009;4:1384-7.
18. Schipperus M, Rijnbeek B, Reddy M, Qin X, Cornfeld MJ. CNTO328 (anti-IL-6mAb) treatment is associated with an increase in hemoglobin and decrease in hepcidin levels in renal cell carcinoma (RCC) [abstract]. Blood 2009;114. Abstract nr 4045.
19. van Rhee F, Fayad L, Voorhees P, Furman R, Lonial S, Borghaei H, et al. Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. J Clin Oncol 2010;28:3701-8.
20. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J 1990;265:621-36.
21. Puchalski T, Prabhakar U, Jiao Q, Berns B, Davis HM. Pharmacokinetic and pharmacodynamic modeling of an anti-interleukin-6 chimeric monoclonal antibody (siltuximab) in patients with metastatic renal cell carcinoma. Clin Cancer Res 2010;16:1652-61.
22. Kurzrock R, Voorhees PM, Casper C, Furman RR, Fayad L, Lonial S, et al. A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res 2013;19:3659-70.
23. Chenillot O, Henny J, Steinmetz J, Herbeth B, Wagner C, Siest G. High sensitivity C-reactive protein: biological variations and reference limits. Clin Chem Lab Med 2000;38:1003-11.
24. Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M. Immunoassay for human serum hepcidin. Blood 2008;112:4292-7.
25. Rossi JF, Negrier S, James ND, Kocak I, Hawkins R, Davis H, et al. A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer. Br J Cancer 2010;103: 1154-62.
26. Xie L, Li LY, Kurzrock R, van Rhee F, Qin X, Reddy M, et al. Population pharmacokinetic and pharmacodynamic modeling of an anti-interleukin- 6 chimeric monoclonal antibody, siltuximab (CNTO 328), in patients with B-cell non-Hodgkin's lymphoma, multiple myeloma, or Castleman's disease. Blood 2012;120:1365.
27. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:1626-34.
28. Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non- small-cell lung cancer. Clin Cancer Res 2007;13:2890-6.
29. Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 2005;41:2502-12.
30. Coward J, Kulbe H, Chakravarty P, Leader D, Vassileva V, Leinster DA, et al. Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res 2011;17:6083-96.
31. Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman's disease. Blood 1989;74:1360-7.