Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer

Cancer Chemotherapy and Pharmacology

Volumn 75, Issue 1, 2015, Pages 17-23

  Hochster, H S ^a   Uboha, N ^a   Messersmith, W ^b   Gold, P J ^c   ONeil, B H ^d   Cohen, D ^e   Denlinger, C ^f   Cohen, S ^f   Leichman, C G ^e   Leichman, L ^e  

^a YALE CANCER CENTER   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c SWEDISH MEDICAL CENTER   (United States)

^d INDIANA UNIVERSITY   (United States)

^e NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^f FOX CHASE CANCER CENTER   (United States)

Author keywords

Colon cancer; Irinotecan; KRAS mutation; Selumetinib

Indexed keywords

BEVACIZUMAB; IRINOTECAN; K RAS PROTEIN; OXALIPLATIN; SELUMETINIB; ANTINEOPLASTIC AGENT; BENZIMIDAZOLE DERIVATIVE; CAMPTOTHECIN; DNA TOPOISOMERASE INHIBITOR; KRAS PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; ONCOPROTEIN; PROTEIN KINASE INHIBITOR; RAS PROTEIN; TUMOR PROTEIN;

ADRENAL INSUFFICIENCY; ADULT; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER MORTALITY; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER SURVIVAL; CAUSE OF DEATH; CHEMOTHERAPY INDUCED ANEMIA; CHEMOTHERAPY INDUCED EMESIS; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; CLINICAL ARTICLE; CLINICAL EVALUATION; COHORT ANALYSIS; COLORECTAL CANCER; CONTROLLED STUDY; DEHYDRATION; DIARRHEA; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; ENTERITIS; EXON; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; GENE MUTATION; HUMAN; MALE; MONOTHERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; OPEN STUDY; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRESYNCOPE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RECOMMENDED DRUG DOSE; RESPIRATORY FAILURE; SEPSIS; SYSTEMIC THERAPY; AGED; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; COLORECTAL NEOPLASMS; DOSE RESPONSE; DRUG RESISTANCE; EARLY TERMINATION OF CLINICAL TRIAL; GENETICS; METABOLISM; MIDDLE AGED; MUTATION; PILOT STUDY; SURVIVAL;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENZIMIDAZOLES; CAMPTOTHECIN; COHORT STUDIES; COLORECTAL NEOPLASMS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, NEOPLASM; EARLY TERMINATION OF CLINICAL TRIALS; FEMALE; HUMANS; MALE; MAP KINASE KINASE KINASES; MIDDLE AGED; MUTATION; NEOPLASM PROTEINS; PILOT PROJECTS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; RAS PROTEINS; SURVIVAL ANALYSIS; TOPOISOMERASE I INHIBITORS;

EID: 84925232383     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-014-2609-3     Document Type: Article

References (28)

1. Siegel R, Naishadham D, Jemal A. (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11-30
2. Muratore A, Zorzi D, Bouzari H et al (2007) Asymptomatic colorectal cancer with un-resectable liver metastases: immediate colorectal resection or up-front systemic chemotherapy? Ann Surg Oncol 14:766-770
3. Kopetz S, Chang GJ, Overman MJ et al (2009) Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 27:3677-3683
4. Renouf DJ, Lim HJ, Speers C et al (2011) Survival for metastatic colorectal cancer in the bevacizumab era: a population-based analysis. Clin Colorectal Cancer 10:97-101
5. Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757-1765
6. Kalady MF, Dejulius KL, Sanchez JA et al (2012) BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis. Dis Colon Rectum 55:128-133
7. Van Cutsem E., Kohne CH, Lang I et al (2011) Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 29:2011-2019
8. Di Nicolantonio F., Martini M, Molinari F et al (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26:5705-5712
9. Tournigand C, Andre T, Achille E et al (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22: 229-237
10. Rajalingam K, Schreck R, Rapp UR et al (2007) Ras oncogenes and their downstream targets. Biochim Biophys Acta 1773:1177-1195
11. Roberts PJ, Der C.J. (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26:3291-3310
12. Migliardi G, Sassi F, Torti D et al (2012) Inhibition of MEK and PI3 K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomas. Clin Cancer Res 18:2515-2525
13. Davies BR, Logie A, McKay JS et al (2007) AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/ extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther 6:2209-2219
14. Adjei AA, Cohen RB, Franklin W et al (2008) Phase I pharmacokinetic and pharmacodynamic study of the oral, smallmolecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol 26:2139-2146
15. Banerji U, Camidge DR, Verheul HM et al (2010) The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): a phase I openlabel multicenter trial in patients with advanced cancer. Clin Cancer Res 16:1613-1623
16. Bennouna J, Lang I, Valladares-Ayerbes M et al (2011) A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens. Invest New Drugs 29:1021-1028
17. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247
18. Kim K, Infante J, Cohen R et al (2011) A phase I dose-escalation study of selumetinib in combination with docetaxel in patients with advanced solid tumors. Mol Cancer Ther 10:Abstract B225
19. Janne PA, Shaw AT, Pereira JR et al (2013) Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 14:38-47
20. Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311-2319
21. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1-10
22. Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337-345
23. Trujillo JI (2011) MEK inhibitors: a patent review 2008-2010. Expert Opin Ther Pat 21:1045-1069
24. Flaherty KT, Robert C, Hersey P et al (2012) Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 367:107-114
25. Britten CD (2013) PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types. Cancer Chemother Pharmacol 71:1395-1409
26. Spreafico A, Tentler JJ, Pitts TM et al (2013) Rational combination of a MEK inhibitor, selumetinib, and the Wnt/calcium pathway modulator, cyclosporin A, in preclinical models of colorectal cancer. Clin Cancer Res 19:4149-4162
27. Morelli MP, Tentler JJ, Kulikowski GN et al (2012) Preclinical activity of the rational combination of selumetinib (AZD6244) in combination with vorinostat in KRAS-mutant colorectal cancer models. Clin Cancer Res 18:1051-1062
28. Balmanno K, Chell SD, Gillings AS et al (2009) Intrinsic resistance to the MEK1/2 inhibitor AZD6244 (ARRY-142886) is associated with weak ERK1/2 signalling and/or strong PI3 K signalling in colorectal cancer cell lines. Int J Cancer 125:2332-2341