Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: Preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer

Journal of Clinical Oncology

Volumn 30, Issue 13, 2012, Pages 1505-1512

  Weickhardt, Andrew J ^a   Price, Tim J ^e   Chong, Geoff ^b   Gebski, Val ^f   Pavlakis, Nick ^f   Johns, Terrance G ^c   Azad, Arun ^b   Skrinos, Effie ^b   Fluck, Kate ^b   Dobrovic, Alexander ^c   Salemi, Renato ^d   Scott, Andrew M ^a   Mariadason, John M ^a   Tebbutt, Niall C ^a,b  

^a LUDWIG INSTITUTE FOR CANCER RESEARCH   (Australia)

^b AUSTIN HEALTH   (Australia)

^c HUDSON INSTITUTE OF MEDICAL RESEARCH   (Australia)

^d QUEEN ELIZABETH HOSPITAL   (Australia)

^e NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL   (Australia)

^f ROYAL NORTH SHORE HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; FLUOROPYRIMIDINE; FLUOROURACIL; IRINOTECAN; K RAS PROTEIN; OXALIPLATIN; STAT3 PROTEIN; ANTINEOPLASTIC AGENT; EGFR PROTEIN, HUMAN; KRAS PROTEIN, HUMAN; MONOCLONAL ANTIBODY; ONCOPROTEIN; PROTEIN KINASE INHIBITOR; QUINAZOLINE DERIVATIVE; RAS PROTEIN; STAT3 PROTEIN, HUMAN;

ADULT; ADVANCED CANCER; AGED; ARTICLE; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CELL VIABILITY; CLINICAL ARTICLE; CLINICAL EVALUATION; COLORECTAL CANCER; CONTROLLED STUDY; DRUG POTENTIATION; DRUG TARGETING; DRUG TOXICITY; FATIGUE; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOMAGNESEMIA; LOADING DRUG DOSE; MALE; METASTATIC COLORECTAL CANCER; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RASH; TREATMENT RESPONSE; WILD TYPE; ANALYSIS OF VARIANCE; AUSTRALIA; CELL PROLIFERATION; CLINICAL TRIAL; COLORECTAL TUMOR; DISEASE FREE SURVIVAL; DRUG ANTAGONISM; DRUG EFFECT; DRUG RESISTANCE; ENZYMOLOGY; GENETIC TRANSFECTION; GENETICS; KAPLAN MEIER METHOD; METABOLISM; MIDDLE AGED; MOLECULARLY TARGETED THERAPY; MORTALITY; MULTICENTER STUDY; MUTATION; PATHOLOGY; SIGNAL TRANSDUCTION; TIME; TREATMENT OUTCOME; TUMOR CELL LINE;

ADULT; AGED; AGED, 80 AND OVER; ANALYSIS OF VARIANCE; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; AUSTRALIA; CELL LINE, TUMOR; CELL PROLIFERATION; COLORECTAL NEOPLASMS; DISEASE-FREE SURVIVAL; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; MOLECULAR TARGETED THERAPY; MUTATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; QUINAZOLINES; RAS PROTEINS; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; TIME FACTORS; TRANSFECTION; TREATMENT OUTCOME;

EID: 84862987061     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2011.38.6599     Document Type: Article

References (36)

1. De Roock W, Claes B, Bernasconi D, et al: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: A retrospective consortium analysis. Lancet Oncol 11:753-762, 2010
2. Karapetis CS, Khambata-Ford S, Jonker DJ, et al: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757-1765, 2008
3. Chau I, Cunningham D, Hickish T, et al: Gefitinib and irinotecan in patients with fluoropyrimidine-refractory, irinotecan-naive advanced colorectal cancer: A phase I-II study. Ann Oncol 18:730-737, 2007 (Pubitemid 46523278)
4. Fisher GA, Kuo T, Cho CD, et al: A phase II study of gefitinib in combination with FOLFOX-4 (IFOX) in patients with metastatic colorectal cancer. J Clin Oncol 22:248s, 2004 (suppl; abstr 3514)
5. Keilholz U, Arnold D, Niederle N, et al: Erlotinib as second and third line monotherapy in patients with metastatic colorectal cancer: Results of a multicenter two-cohort phase II trial. J Clin Oncol 23:263s, 2005 (suppl; abstr 3575)
6. Rothenberg ML, LaFleur B, Levy DE, et al: Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J Clin Oncol 23:9265-9274, 2005
7. Zampino MG, Lorizzo K, Massacesi C, et al: First-line gefitinib combined with simplified FOLFOX-6 in patients with epidermal growth factor receptor-positive advanced colorectal cancer. J Clin Oncol 23:259s, 2005 (suppl; abstr 3659)
8. Matar P, Rojo F, Cassia R, et al: Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): Superiority over single-agent receptor targeting. Clin Cancer Res 10:6487-6501, 2004 (Pubitemid 39346544)
9. Gan HK, Walker F, Burgess AW, et al: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 increases the formation of inactive untethered EGFR dimmers: Implications for combination therapy with monoclonal antibody 806. J Biol Chem 282:2840-2850, 2007 (Pubitemid 47084315)
10. Johns TG, Luwor RB, Murone C, et al: Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced by the EGF receptor inhibitor AG1478. Proc Natl Acad Sci U S A 100:15871-15876, 2003 (Pubitemid 38021082)
11. Blackwell KL, Burstein HJ, Storniolo AM, et al: Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol 28:1124-1130, 2010
12. Baselga J, Bradbury I, Eidtmann H, et al: First results of the NeoALTTO Trial (BIG 01-06/EGF 106903): A phase III, randomized, open label, neo-adjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. 2010 San Antonio Breast Cancer Symposium, San Antonio, TX, December 6-10, 2010 (abstr S3-3)
13. Avallone A, Di Gennaro E, Bruzzese F, et al: Synergistic antitumour effect of raltitrexed and 5-fluorouracil plus folinic acid combination in human cancer cells. Anticancer Drugs 18:781-791, 2007 (Pubitemid 46975964)
14. Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27-55, 1984
15. Magné N, Fischel JL, Dubreuil A, et al: Sequence-dependent effects of ZD1839 ('Iressa') in combination with cytotoxic treatment in human head and neck cancer. Br J Cancer 86:819-827, 2002 (Pubitemid 34250828)
16. Mariadason JM, Rickard KL, Barkla DH, et al: Divergent phenotypic patterns and commitment to apoptosis of Caco-2 cells during spontaneous and butyrate-induced differentiation. J Cell Physiol 183:347-354, 2000 (Pubitemid 30243865)
17. Edgar KA, Wallin JJ, Berry M, et al: Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors. Cancer Res 70:1164-1172, 2010
18. Wilson AJ, Chueh AC, Togel L, et al: Apoptotic sensitivity of colon cancer cells to histone deacetylase inhibitors is mediated by an Sp1/Sp3-activated transcriptional program involving immediate-early gene induction. Cancer Res 70:609-620, 2010
19. Takeda T, Kurachi H, Yamamoto T, et al: Crosstalk between the interleukin-6 (IL-6)-JAK-STAT and the glucocorticoid-nuclear receptor pathway: Synergistic activation of IL-6 response element by IL-6 and glucocorticoid. J Endocrinol 159:323-330, 1998 (Pubitemid 28520186)
20. Guarino MJ, Schneider CJ, Hosford MA, et al: Dual inhibition of the epidermal growth factor receptor pathway with cetuximab and erlotinib: A phase I study in patients with advanced solid malignancies. Oncologist 14:119-124, 2009
21. Lin CC, Calvo E, Papadopoulos KP, et al: Phase I study of cetuximab, erlotinib, and bevacizumab in patients with advanced solid tumors. Cancer Chemother Pharmacol 63:1065-1071, 2009
22. Do H, Krypuy M, Mitchell PL, et al: High resolution melting analysis for rapid and sensitive EGFR and KRAS mutation detection in formalin fixed paraffin embedded biopsies. BMC Cancer 8:142, 2008
23. Zhong Z, Wen Z, Darnell JE Jr: Stat3: A STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264:95-98, 1994 (Pubitemid 24144493)
24. Niu G, Wright KL, Huang M, et al: Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 21:2000-2008, 2002 (Pubitemid 34270888)
25. Baselga J, Schoffski P, Rojo F, et al: A phase I pharmacokinetic (PK) and molecular pharmacodynamic (PD) study of the combination of two anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts) with advanced colorectal (CRC), head and neck (HNC) and non-small cell lung cancer (NSCLC). J Clin Oncol 24:122s, 2006 (suppl; abstr 3006)
26. Reference deleted
27. Rizzo S, Bronte G, Fanale D, et al: Prognostic vs predictive molecular biomarkers in colorectal cancer: Is KRAS and BRAF wild type status required for anti-EGFR therapy? Cancer Treat Rev 36:S56-S61, 2010 (suppl 3)
28. Scaltriti M, Verma C, Guzman M, et al: Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene 28:803-814, 2009
29. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al: Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040-2048, 2007 (Pubitemid 350106711)
30. Van Cutsem E, Peeters M, Siena S, et al: Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658-1664, 2007 (Pubitemid 46797944)
31. Lacouture ME, Mitchell EP, Piperdi B, et al: Skin Toxicity Evaluation Protocol With Panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol 28:1351-1357, 2010
32. Saltz LB, Meropol NJ, Loehrer PJ Sr, et al: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201-1208, 2004 (Pubitemid 41079832)
33. Tejpar S, Peeters M, Humblet Y, et al: Relationship of efficacy with KRAS status (wild type versus mutant) in patients with irinotecan-refractory metastatic colorectal cancer (mCRC), treated with irinotecan (q2w) and escalating doses of cetuximab (q1w): The EVEREST experience (preliminary data). J Clin Oncol 26:178s, 2008 (suppl; abstr 4001)
34. Tejpar S, Piessevaux H, Claes K, et al: Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: A prospective study. Lancet Oncol 8:387-394, 2007 (Pubitemid 46621761)
35. Vincenzi B, Santini D, Galluzzo S, et al: Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab plus irinotecan as predictive factor of efficacy and outcome. Clin Cancer Res 14:4219-4224, 2008
36. Vickers MM, Karapetis CS, Tu D, et al: The influence of hypomagnesemia (hMg) on overall survival (OS) in a phase III randomized study of cetuximab (CET) plus best supportive care (BSC) versus BSC: NCIC CTG/AGITG CO.17. J Clin Oncol 29:246s, 2011 (suppl; abstr 3601)