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1.
Clin Cancer Res ; 21(11): 2530-7, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-25724520

ABSTRACT

PURPOSE: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. EXPERIMENTAL DESIGN: This randomized phase II trial enrolled 78 FIGO stage IB2-IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. RESULTS: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). CONCLUSIONS: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups.


Subject(s)
Cetuximab/administration & dosage , Chemoradiotherapy , Phosphatidylinositol 3-Kinases/genetics , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , AMP-Activated Protein Kinase Kinases , Adult , Aged , Cisplatin/administration & dosage , Class I Phosphatidylinositol 3-Kinases , Disease-Free Survival , Female , Humans , Middle Aged , Mutation , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Signal Transduction/drug effects , Uterine Cervical Neoplasms/pathology , ras Proteins/genetics
2.
Anticancer Res ; 30(10): 4229-35, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21036746

ABSTRACT

KRAS somatic mutations are the main predictive factor for non response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination.


Subject(s)
Adenocarcinoma/genetics , Colonic Neoplasms/genetics , Genes, ras , Mutation , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/pathology , DNA Mutational Analysis , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Polymerase Chain Reaction , Proto-Oncogene Proteins B-raf/genetics , Young Adult
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