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As expected, consistently favourable efficacy was observed in patients with KRAS WT versus MT tumours receiving first-line panitumumab plus FOLFIRI treatment.

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NCT00598156.

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We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, Ecadherin, ␤-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Colorectal cancer is estimated to be the second leading cause of cancer death worldwide. 1 Differences in etiology, clinical behavior, pathologic features and genetic alterations apply to right-sided vs. left-sided colorectal tumors, which indicate that different mechanisms drive tumorigenesis at these sites. 2,3 Approximately 35% of colorectal cancers are located in the rectum, and rectal cancer affects males at a rate of 1.5:1 compared to females, with 75% of cases diagnosed after 65 years of age. Treatment advances such as the standardized surgical technique TME, preoperative radiotherapy and adjuvant chemotherapy have reduced the previously high local recurrence rate and improved survival in rectal cancer patients. Despite these advances, about 40% of patients still die from disseminated disease. 4 -6 Hence, there is a need for novel markers that allow improved identification of high-risk patients who would benefit from adjuvant treatment. 7 Colorectal cancer is one of the best-characterized tumor types at the molecular level. Numerous genetic alterations in oncogenes, tumor-suppressor genes and DNA MMR genes are acquired during tumorigenesis, which occurs through successive waves of clonal expansion according to 2 major mutational pathways, the CIN and MSI pathways. 8,9 Although the sequential accumulation of genetic changes that characterize the adenoma-carcinoma sequence of colorectal cancer applies also to rectal cancer, few studies have separately analyzed these tumor types. Rectal cancer has been associated with high proliferative activity, frequent aneuploidy and loss of heterozygosity at 17p and 18q, mutation/overexpression of p53 and consequently low frequencies of diploid tumors and MSI. 2,3,10 -12 Since the frequencies of the different genetic alterations vary according to tumor location within the bowel, studies investigating a possible prognostic role of biologic parameters should optimally analyze these tumor types separately.Several tumor-associated proteins may be relevant prognostic markers in rectal cancer. However, no single molecular marker has been demonstrated to provide consistent and independent prognostic information, and despite advances in our understanding of the pathogenesis of rectal cancer, molecular markers have not gained utility in clinical decision making. 7,13,14 The TMA technology allows high-throughput analysis of molecular markers and thereby facilitates studies of multiple markers in large tumor series. 15 Our aim was to apply TMA to investigate the expression patterns of multiple markers and their prognostic correlations in a large series of rectal cancer patients. These markers, which included Ki-67, p53, Bcl-2, EGF...

BackgroundIntegument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial.MethodsIntegument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity.Results154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity.ConclusionsFirst-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity.Trial registrationClinicalTrials.gov NCT00508404