scholarly journals A Phase II Study of Panitumumab Plus Irinotecan for Metastatic Colorectal Cancer Patients with Wild KRAS Exon 2, Resistant to Fluoropyrimidine, Oxaliplatin and Irinotecan in Japanese. (OGSG1001)

2014 ◽  
Vol 25 ◽  
pp. ii89
Author(s):  
Hata Taishi ◽  
Yoshida Motoki ◽  
Taira Koichi ◽  
Sugimoto Naotoshi ◽  
Tokunaga Yukihiko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Exon 2 ◽  
Colorectal Cancer Patients ◽  
Kras Exon

scholarly journals KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan: Molecular spectrum, frequency and distribution pattern

2019 ◽  
Author(s):  
Muhammad Awidi ◽  
Nidaa Ababneh ◽  
Maha Shomaf ◽  
Feras Al Fararjeh ◽  
Laila Owaidi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Distribution Pattern ◽  
Cancer Patients ◽  
Molecular Spectrum ◽  
Kras Mutations ◽  
Exon 2 ◽  
Ras Mutations ◽  
Colorectal Cancer Patients ◽  
Kras Exon

Abstract Background A constitutively active RAS protein in the absence of stimulation of the epidermal growth factor receptor (EGFR) is the result of mutations in KRAS and NRAS genes. Mutations in the KRAS exon 2 and outside exon 2 have been found to predict the resistance to anti-EGFR monoclonal therapy. A substantial proportion of metastatic colorectal cancer cases (mCRC) exhibit RAS mutations outside KRAS exon 2, particularly in KRAS exon 3 and 4 and NRAS exons 2, 3. No data about RAS mutations outside KRAS exon 2 are available for Jordanian patients with mCRC. We aim to study the molecular spectrum, frequency, and distribution pattern of KRAS and NRAS mutations in Jordanian patients with mCRC. Methods A cohort of 190 Jordanian metastatic colorectal cancer patients were enrolled in the trial. We detected mutations in exon 2 of the KRAS and NRAS gene as well as mutations outside of exon 2 using the StripAssay technique. The KRAS StripAssay covered 29 mutations and 22 NRAS mutations. Results Mutations were observed in 92 (48.42%) cases, and KRAS exon 2 accounted for 76 cases (83.69%). KRAS G12D was the most common mutation, occurring in 18 cases, followed by KRAS G12A in 16 cases, and G12T in 13 cases. Mutations outside of KRAS exon 2 represented 16.3% of the mutated cases. Among those, 6 cases (6.48%) carried mutations in NRAS exon 2, 3 and 10 cases (10.87%) in KRAS exon 3 and 4. Conclusion The frequency of NRAS and KRAS mutations outside of exon 2 appears to be higher in Jordanian patients in comparison with patients from western countries. KRAS mutations outside of exon 2 should be tested routinely to identify patients who should not be treated with anti-EGFR antibodies.

scholarly journals A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients

2019 ◽  
Vol 121 (5) ◽  
pp. 378-383 ◽  
Author(s):  
Elena Elez ◽  
Carles Pericay ◽  
Manuel Valladares-Ayerbes ◽  
Inmaculada Bando ◽  
Maria Jose Safont ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Salvage Therapy ◽  
Phase 2 ◽  
Wild Type ◽  
Exon 2 ◽  
Phase 2 Study ◽  
Colorectal Cancer Patients ◽  
Kras Exon

scholarly journals Phase II study of weekly irinotecan and capecitabine treatment in metastatic colorectal cancer patients

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Wenhua Li ◽  
Jianming Xu ◽  
Lin Shen ◽  
Tianshu Liu ◽  
Weijian Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Colorectal Cancer Patients

Safety and efficacy of the addition of simvastatin to panitumumab in KRAS mutant metastatic colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14558-e14558
Author(s):  
Henk-jan Guchelaar ◽  
Jara M Baas ◽  
Lisanne Krens ◽  
Monique M.E.M. Bos ◽  
Johanna Elisabeth A. Portielje ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Colorectal Tumors ◽  
Wild Type ◽  
Kras Gene ◽  
Once Daily ◽  
Colorectal Cancer Patients

e14558 Background: Epithelial growth factor receptor (EGFR) inhibitors are not effective in KRAS mutant colorectal tumors. In these tumors the k-ras protein is activated by post-translational modification by binding farnesyl (C15) and geranylgeranyl (C17) moieties. Both are products of the mevalonate pathway, as is cholesterol. Statins (HMG-CoA-reductase inhibitors) not only inhibit synthesis of cholesterol, but also of C15 and C17 and thus may relevantly inhibit post-translational activation of ras proteins. Therefore, statins may inhibit the expression of the mutant KRAS phenotype and normalize the phenotype into KRAS wild type. In a phase II study we investigated whether simvastatin treatment renders KRAS mutant colorectal tumors sensitive to panitumumab. Methods: Major eligibility criteria were advanced or metastatic colorectal cancer failing prior 5FU, oxaliplatin and irinotecan containing regimens, with a mutation in codon 12, 13 or 61 of KRAS gene on tumor sample. Patients were treated with simvastatin 80mg once daily and panitumumab 6mg/kg every 2 weeks. Primary objective was to investigate the percentage of patients free from progression and alive 11 weeks after the first administration of panitumumab. This phase II study was performed in a Simon two stage design, performing an interim analysis after the enrolment of 15 patients. When at least 6 of these patients (i.e. 40%) were to be alive and free from progression free at 11 weeks after the first administration of panitumumab (similar to the results of the KRAS wild type population of the phase III study), another 31 patients would be included during stage 2. Results: Fifteen evaluable patients were enrolled by 4 study sites. Only one patient was free from progression 11 weeks after start of panitumumab treatment (6.7%). Mean progression free survival was 9.1 weeks (range 5-17 weeks). Most frequent reported side effect was skin toxicity (40%), one patient experienced myositis grade 3. Conclusions: Simvastatin 80mg once daily was not able to inhibit the KRAS mutant phenotype sufficiently to reach sensitivity to panitumumab in colorectal cancer patients with a mutation in the KRAS gene. Clinical trial information: NCT01110785.

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