Phase i clinical trial of the anti-EGFR monoclonal antibody nimotuzumab with concurrent external thoracic radiotherapy in Canadian patients diagnosed with stage IIb, III or IV non-small cell lung cancer unsuitable for radical therapy

Cancer Chemotherapy and Pharmacology

Volumn 67, Issue 4, 2011, Pages 837-845

  Bebb, Gwyn ^a   Smith, Colum ^b   Rorke, Stewart ^c   Boland, William ^d   Nicacio, Leonardo ^e   Sukhoo, Ryan ^e   Brade, Anthony ^f  

^a UNIVERSITY OF CALGARY   (Canada)

^b SASKATCHEWAN CANCER AGENCY   (Canada)

^c Dr H Bliss Murphy Cancer Centre   (Canada)

^d MCGILL UNIVERSITY   (Canada)

^e YM BioSciences Inc   (Canada)

^f UNIVERSITY OF TORONTO   (Canada)

Author keywords

Clinical trial; Monoclonal antibody; Nimotuzumab; Non small cell lung cancer; Toxicity

Indexed keywords

NIMOTUZUMAB;

AGED; ALKALINE PHOSPHATASE BLOOD LEVEL; ANOREXIA; APHASIA; ARTICLE; CANADA; CANCER CONTROL; CANCER RADIOTHERAPY; CANCER STAGING; CHILL; CLINICAL ARTICLE; CONSTIPATION; DRUG DOSE ESCALATION; DRUG ERUPTION; DRUG HYPERSENSITIVITY; DRUG MEGADOSE; DRUG SAFETY; DYSPNEA; ESOPHAGUS DISEASE; FATIGUE; FEMALE; HUMAN; HYPERGLYCEMIA; HYPOMAGNESEMIA; HYPOPHOSPHATEMIA; HYPOXIA; LUNG NON SMALL CELL CANCER; MALE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; PAIN; PALLIATIVE THERAPY; PHASE 1 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; RADIATION FIELD; RADIATION PNEUMONIA; SIDE EFFECT; SKIN TOXICITY; TREATMENT RESPONSE; WALKING DIFFICULTY; WEIGHT REDUCTION;

AGED; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CANADA; CARCINOMA, NON-SMALL-CELL LUNG; COMBINED MODALITY THERAPY; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; LUNG NEOPLASMS; MALE; NEOPLASM STAGING; PALLIATIVE CARE; RADIATION DOSAGE; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 79954442316     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00280-010-1379-9     Document Type: Article

References (41)

1. A Jemal R Siegel E Ward T Murray J Xu MJ Thun 2007 Cancer statistics, 2007 CA Cancer J Clin 57 1 43 66 17237035 10.3322/canjclin.57.1.43 (Pubitemid 46148091)
2. A Fairchild K Harris E Barnes R Wong S Lutz A Bezjak, et al. 2008 Palliative thoracic radiotherapy for lung cancer: a systematic review J Clin Oncol 26 24 4001 4011 18711191 10.1200/JCO.2007.15.3312
3. AM Quddus GR Kerr A Price A Gregor 2001 Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy Clin Oncol (R Coll Radiol) 13 2 95 98 1:STN:280:DC%2BD3M3ptFaitA%3D%3D
4. A Bezjak P Dixon M Brundage D Tu MJ Palmer P Blood, et al. 2002 Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15) Int J Radiat Oncol Biol Phys 54 3 719 728 12377323 10.1016/S0360-3016(02)02989-9
5. M Fukuoka S Yano G Giaccone T Tamura K Nakagawa JY Douillard, et al. 2003 Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer J Clin Oncol 21 12 2237 2246 12748244 10.1200/JCO.2003.10.038 1:CAS:528:DC%2BD2cXpsVGqu7w%3D (Pubitemid 46621858)
6. JR Grandis JC Sok 2004 Signaling through the epidermal growth factor receptor during the development of malignancy Pharmacol Ther 102 1 37 46 15056497 10.1016/j.pharmthera.2004.01.002 1:CAS:528:DC%2BD2cXisl2ktL8%3D (Pubitemid 38429984)
7. ES Kim V Hirsh T Mok MA Socinski R Gervais YL Wu, et al. 2008 Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial Lancet 372 9652 1809 1818 19027483 10.1016/S0140-6736(08)61758-4 1:CAS:528:DC%2BD1cXhsVWhtbjM
8. TS Mok YL Wu S Thongprasert CH Yang DT Chu N Saijo, et al. 2009 Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma N Engl J Med 361 10 947 957 19692680 10.1056/NEJMoa0810699 1:CAS:528:DC%2BD1MXhtVygsbfK
9. FA Shepherd J Rodrigues Pereira T Ciuleanu EH Tan V Hirsh S Thongprasert, et al. 2005 Erlotinib in previously treated non-small-cell lung cancer N Engl J Med 353 2 123 132 16014882 10.1056/NEJMoa050753 1:CAS:528:DC%2BD2MXmtFaksbo%3D (Pubitemid 41058344)
10. CA Butts D Bodkin EL Middleman CW Englund D Ellison Y Alam, et al. 2007 Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer J Clin Oncol 25 36 5777 5784 18089875 10.1200/JCO.2007.13.0856 1:CAS:528:DC%2BD1cXnsFOgsg%3D%3D
11. R Pirker M Filipits 2009 Targeted therapies in lung cancer Curr Pharm Des 15 2 188 206 19149612 10.2174/138161209787002915 1:CAS:528:DC%2BD1MXjvVOmsrg%3D
12. R Pirker JR Pereira A Szczesna J von Pawel M Krzakowski R Ramlau, et al. 2009 Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial Lancet 373 9674 1525 1531 19410716 10.1016/S0140-6736(09)60569-9 1:CAS:528:DC%2BD1MXltlaqurs%3D
13. AL Agero SW Dusza C Benvenuto-Andrade KJ Busam P Myskowski AC Halpern 2006 Dermatologic side effects associated with the epidermal growth factor receptor inhibitors J Am Acad Dermatol 55 4 657 670 17010747 10.1016/j.jaad.2005.10.010 (Pubitemid 44436627)
14. E Van Cutsem S Siena Y Humblet JL Canon J Maurel E Bajetta, et al. 2008 An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy Ann Oncol 19 1 92 98 17785764 10.1093/annonc/mdm399
15. T Crombet L Torres E Neninger M Catala ME Solano A Perera, et al. 2003 Pharmacological evaluation of humanized anti-epidermal growth factor receptor, monoclonal antibody h-R3, in patients with advanced epithelial-derived cancer J Immunother 26 2 139 148 12616105 10.1097/00002371-200303000-00006 1:CAS:528:DC%2BD3sXhs1agsbY%3D (Pubitemid 36292784)
16. T Crombet-Ramos J Rak R Perez A Viloria-Petit 2002 Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: a humanized anti-EGFR antibody Int J Cancer 101 6 567 575 12237899 10.1002/ijc.10647 1:CAS:528: DC%2BD38Xns1eqsrs%3D
17. LA Torres A Perera JF Batista A Hernandez T Crombet M Ramos, et al. 2005 Phase I/II clinical trial of the humanized anti-EGF-r monoclonal antibody h-R3 labelled with 99mTc in patients with tumour of epithelial origin Nucl Med Commun 26 12 1049 1057 16264350 10.1097/00006231-200512000-00002 1:CAS:528: DC%2BD2MXhtFKqtrzL (Pubitemid 41677593)
18. T Crombet J Figueredo M Catala S González JC Selva T Cruz, et al. 2006 Treatment of high-grade glioma patients with the humanized anti-epidermal growth factor receptor (EGFR) antibody h-R3: report from a phase I/II trial Cancer Biol Ther 5 4 375 379 10.4161/cbt.5.4.2522
19. Bode U, Buchen S, Warmuth-Metz M, Pietsch T, Bach F, Fleischhack G (2007) Final report of a phase II trial of nimotuzumab in the treatment of refractory and relapsed high-grade gliomas in children and adolescents. J Clin Oncol 25(18S, Part 1, June 20 Suppl: Abstr 2006)
20. Bode U, Windelberg M, Massimino M, Khuhlaeva E, Warmuth-Metz M, Kortmann RD et al (2008) Phase III trial of nimotuzumab for the treatment of newly diagnosed diffuse intrinsic pontine gliomas in children and adolescents. J Clin Oncol 26(May 20 Suppl; abstr 2058)
21. T Crombet M Osorio T Cruz C Roca R del Castillo R Mon, et al. 2004 Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients J Clin Oncol 22 9 1646 1654 15117987 10.1200/JCO.2004.03. 089 (Pubitemid 41079803)
22. Y Akashi I Okamoto T Iwasa T Yoshida M Suzuki E Hatashita, et al. 2008 Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status Br J Cancer 98 4 749 755 18253126 10.1038/sj.bjc.6604222 1:CAS:528:DC%2BD1cXitVGhtLo%3D (Pubitemid 351272610)
23. WK Boland G Bebb 2009 Nimotuzumab: a novel anti-EGFR monoclonal antibody that retains anti-EGFR activity while minimizing skin toxicity Expert Opin Biol Ther 9 9 1199 1206 19624281 10.1517/14712590903110709 1:CAS:528: DC%2BD1MXptlyktbk%3D
24. You B, Brade A, Magalhaes JM, Siu LL, Oza A, Lovell S, Wang L, Hedley DW, Nicacio LV, Chen EX (2010) A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies. Invest New Drugs. doi: 10.1007/s10637-010-9444-0
25. Reddy BK, Vidyasagar M, Shenoy K, Fernandes D, Vadhiraja B, Halsnad S et al (2007) Nimotuzumab (h-R3) in combination with chemoradiotherapy and radiotherapy in the treatment of squamous cell carcinoma of head and neck (SCCHN). http://astro2007.abstractsnet.com/handouts/500467-Biocon-h-R3.pdf
26. Rojo F, Gracias E, Villena N, Cruz T, Corradino I, Cedeño M et al (2008) Pharmacodynamic study of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN): A SENDO foundation study. J Clin Oncol 26(May 20 Suppl; abstr 6070)
27. F Macbeth 1996 Comments on A case of radiation myelopathy after 2 × 8.5 Gy for inoperable non-small cell lung cancer, Dardoufas et al., European Journal of Cancer, 31A, Nos 13/14, pp. 2418-2419, 1995 Eur J Cancer 32A 9 1616 1617 8911129 10.1016/S0959-8049(96)90058-1 1:STN:280:DyaK2s%2FmslOrsw%3D%3D
28. Macbeth FR, Wheldon TE, Girling DJ, Stephens RJ, Machin D, Bleehen NM et al. (1996) Radiation myelopathy: estimates of risk in 1048 patients in three randomized trials of palliative radiotherapy for non-small cell lung cancer. The medical research council lung cancer working party. Clin Oncol (R Coll Radiol) 8(3): 176-181 (Pubitemid 26248532)
29. Brundage MD, Bezjak A, Dixon P, Grimard L, Larochelle M, Warde P et al (1996) The role of palliative thoracic radiotherapy in non-small cell lung cancer. Can J Oncol 6(Suppl 1): 25-32
30. Prepared on behalf of the Medical Research Council Lung Cancer Working Party and all its collaborators by Bleehen NM, Girling DJ, Machin D, Stephens RJ (1992) A Medical Research Council (MRC) randomised trial of palliative radiotherapy with two fractions or a single fraction in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status. Br J Cancer 65(6):934-941
31. P Therasse SG Arbuck EA Eisenhauer J Wanders RS Kaplan L Rubinstein, et al. 2000 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 92 3 205 216 10655437 10.1093/jnci/92.3.205 1:STN:280: DC%2BD3c7it1Gitg%3D%3D
32. N Boku K Yamazaki N Yamamoto T Takahashi A Fukutomi M Miyazaki T Satoh I Okamoto K Nakagawa M Fukuoka 2009 Phase I study of nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody in patients with solid tumors in Japan J Clin Oncol 27 15 Suppl e14574
33. Tikhomirov I, Garrido G, Yang E, Sherman I, Perez R (2008) Bivalent binding properties of epidermal growth factor receptor (EGFR) targeted monoclonal antibodies: factors contributing to differences in observed clinical profiles. AACR Cancer Clinical Trials and Personalized Medicine (abstr A36)
34. Garrido G, Rabasa A, Gracia E, Tikhomirov I, Crombet-Ramos T, Viloria-Petit A et al. (2009) Binding properties of the anti-EGFR monoclonal antibody, nimotuzumab, limit its interaction with the EGFR in renal and epidermal cells. AACR 100th Annual Meeting, (Abstr 2763)
35. S Aviel-Ronen FH Blackhall FA Shepherd MS Tsao 2006 K-ras mutations in non-small-cell lung carcinoma: a review Clin Lung Cancer 8 1 30 38 16870043 10.3816/CLC.2006.n.030 1:CAS:528:DC%2BD28XovFGisbk%3D (Pubitemid 44336241)
36. RG Amado M Wolf M Peeters E Van Cutsem S Siena DJ Freeman, et al. 2008 Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer J Clin Oncol 26 10 1626 1634 18316791 10.1200/JCO.2007.14.7116 1:CAS:528:DC%2BD1cXltlWhsrw%3D
37. O'Byrne KJ, Bondarenko I, Barrios C, Eschbach C, Martens U, Hotko Y, Celik I, Stroh C, Pirker R (2009) Molecular and clinical predictors of outcome for cetuximab in non-small cell lung cancer(NSCLC): data from the FLEX study. J Clin Oncol 27(15s): p Suppl; Abs 80078
38. M Toulany M Baumann HP Rodemann 2007 Stimulated PI3K-AKT signaling mediated through ligand or radiation-induced EGFR depends indirectly, but not directly, on constitutive K-ras activity Mol Cancer Res 5 8 863 872 17699110 10.1158/1541-7786.MCR-06-0297 1:CAS:528:DC%2BD2sXptVWhs74%3D (Pubitemid 47294813)
39. M Toulany U Kasten-Pisula I Brammer S Wang J Chen K Dittmann, et al. 2006 Blockage of epidermal growth factor receptor-phosphatidylinositol 3-kinase-AKT signaling increases radiosensitivity of K-RAS mutated human tumor cells in vitro by affecting DNA repair Clin Cancer Res 12 13 4119 4126 16818713 10.1158/1078-0432.CCR-05-2454 1:CAS:528:DC%2BD28XmsVaks7g%3D (Pubitemid 44078101)
40. A López-Albaitero SC Lee S Morgan JR Grandis WE Gooding S Ferrone RL Ferris 2009 Role of polymorphic Fc gamma receptor IIIa and EGFR expression level in cetuximab mediated, NK cell dependent in vitro cytotoxicity of head and neck squamous cell carcinoma cells Cancer Immunol Immunother 58 11 1855 1864
41. F Bibeau E Lopez-Crapez F Di Fiore S Thezenas M Ychou F Blanchard, et al. 2009 Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan J Clin Oncol 27 7 1122 1129 19164213 10.1200/JCO.2008.18.0463 1:CAS:528:DC%2BD1MXktVCisr8%3D