title: A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory, KRAS Wild-Type, Metastatic Colorectal Cancer.
abstract: Insulin-like growth factor type 1 receptor (IGF-1R) mediates resistance to epidermal growth factor receptor (EGFR) inhibition and may represent a therapeutic target. We conducted a multicenter, randomized, double blind, phase II/III trial of dalotuzumab, an anti-IGF-1R monoclonal antibody, with standard therapy in chemo-refractory, KRAS wild-type metastatic colorectal cancer.
  
  
  
  Eligible patients were randomly assigned to dalotuzumab 10mg/kg weekly (arm A), dalotuzumab 7.5mg/kg every alternate week (arm B), or placebo (arm C) in combination with cetuximab and irinotecan. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included exploratory biomarker analyses. All statistical tests were two-sided.
  
  
  
  The trial was prematurely discontinued for futility after 344 eligible KRAS wild-type patients were included in the primary efficacy population (arm A = 116, arm B = 117, arm C = 111). Median PFS was 3.9 months in arm A (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 0.98 to 1.83, P = .07) and 5.4 months in arm B (HR = 1.13, 95% CI = 0.83 to 1.55, P = .44) compared with 5.6 months in arm C. Median OS was 10.8 months in arm A (HR = 1.41, 95% CI = 0.99 to 2.00, P = .06) and 11.6 months in arm B (HR = 1.26, 95% CI = 0.89 to 1.79, P = .18) compared with 14.0 months in arm C. Grade 3 or higher asthenia and hyperglycaemia occurred more frequently with dalotuzumab compared with placebo. In exploratory biomarker analyses, patients with high IGF-1 mRNA tumors in arm A had numerically better PFS (5.6 vs 3.6 months, HR = 0.59, 95% CI = 0.28 to 1.23, P = .16) and OS (17.9 vs 9.4 months, HR = 0.67, 95% CI = 0.31 to 1.45, P = .31) compared with those with high IGF-1 mRNA tumors in arm C. In contrast, in arm C high IGF-1 mRNA expression predicted lower response rate (17.6% vs 37.3%, P = .04), shorter PFS (3.6 vs 6.6 months, HR = 2.15, 95% CI = 1.15 to 4.02, P = .02), and shorter OS (9.4 vs 15.5 months, HR = 2.42, 95% CI = 1.21 to 4.82, P = .01).
  
  
  
  Adding dalotuzumab to irinotecan and cetuximab was feasible but did not improve survival outcome. IGF-1R ligands are promising biomarkers for differential response to anti-EGFR and anti-IGF-1R therapies.
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Francesco
authors.initials: F
authors.lastname: Sclafani
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Tae Y
authors.initials: TY
authors.lastname: Kim
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM). david.cunningham@rmh.nhs.uk.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Tae W
authors.initials: TW
authors.lastname: Kim
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schmoll
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Jae K
authors.initials: JK
authors.lastname: Roh
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Sun Y
authors.initials: SY
authors.lastname: Kim
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Young S
authors.initials: YS
authors.lastname: Park
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Tormod K
authors.initials: TK
authors.lastname: Guren
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Eliza
authors.initials: E
authors.lastname: Hawkes
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clarke
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: David
authors.initials: D
authors.lastname: Ferry
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Frödin
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Mark
authors.initials: M
authors.lastname: Ayers
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Michael
authors.initials: M
authors.lastname: Nebozhyn
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Clare
authors.initials: C
authors.lastname: Peckitt
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: Andrey
authors.initials: A
authors.lastname: Loboda
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: David J
authors.initials: DJ
authors.lastname: Mauro
authors.affiliation: The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DC, EH, CP, DJW); Seoul National University College of Medicine, Seoul, Korea (TYK); Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (TWK); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, Halle, Germany (HJS); Yonsey Cancer Center, Yonsey University, College of Medicine, Seoul, Korea (JKR); Center for Colorectal Cancer, National Cancer Center, Seoul, Korea (SYK); Samsung Medical Center, Seoul, Korea (YSP); Oslo University Hospital, Oslo, Norway (TKG); Concord Repatriation General Hospital, Concord, Sydney, Australia (SJC); New Cross Hospital, Wolverhamptom, UK (DF); Karolinska University Hospital, Stockholm, Sweden (JEF); Merck & Co., Inc., Whitehouse Station, NJ (MA, MN, AL, DJM).
authors.forename: David J
authors.initials: DJ
authors.lastname: Watkins
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005240:Feasibility Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C569480:dalotuzumab; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin