scholarly journals Panitumumab-Induced Eruptive Seborrhoeic Keratosis in a Patient with Metastatic Colorectal Cancer

2020 ◽  
Author(s):  
Dimitra Koumaki ◽  
Sotirios Boumpoucheropoulos ◽  
Vasiliki Koumaki ◽  
Alexander Katoulis ◽  
Georgia Pappas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Wild Type ◽  
Case Presentation ◽  
First Case ◽  
Stage 4 ◽  
Seborrhoeic Keratosis ◽  
Epidermal Growth ◽  
Emerging Therapy

Objectives: Agents targeting the epidermal growth factor receptor (EGFR)-mediated signalling pathway are increasingly being used for the treatment of advanced lung, pancreatic, colorectal and head and neck cancers. Case presentation: Here, we report the first case of eruptive seborrhoeic keratosis following panitumumab treatment, an anti-EGFR monoclonal antibody, in a 73-year-old patient with stage 4 (IV) colorectal cancer with hepatic metastasis. Conclusion: While panitumumab is an emerging therapy for RAS wild-type metastatic colorectal cancer, physicians should consider panitumumab as a potential cause of eruptive seborrhoeic keratosis.

scholarly journals Metformin selectively inhibits metastatic colorectal cancer with theKRASmutation by intracellular accumulation through silencing MATE1

2020 ◽  
Vol 117 (23) ◽  
pp. 13012-13022 ◽  
Author(s):  
Jinye Xie ◽  
Liangping Xia ◽  
Wei Xiang ◽  
Wenzhuo He ◽  
Haofan Yin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Antitumor Agent ◽  
Wild Type ◽  
Poor Overall Survival ◽  
Patients With Diabetes ◽  
Epidermal Growth ◽  
Anticancer Response

Metastatic colorectal cancer (mCRC) patients have poor overall survival despite using irinotecan- or oxaliplatin-based chemotherapy combined with anti-EGFR (epidermal growth factor receptor) drugs, especially those with the oncogene mutation ofKRAS. Metformin has been reported as a potentially novel antitumor agent in many experiments, but its therapeutic activity is discrepant and controversial so far. Inspiringly, the median survival time forKRAS-mutation mCRC patients with diabetes on metformin is 37.8 mo longer than those treated with other hypoglycemic drugs in combination with standard systemic therapy. In contrast, metformin could not improve the survival of mCRC patients with wild-typeKRAS. Interestingly, metformin is preferentially accumulated inKRAS-mutation mCRC cells, but not wild-type ones, in both primary cell cultures and patient-derived xenografts, which is in agreement with its tremendous effect inKRAS-mutation mCRC. Mechanistically, the mutated KRAS oncoprotein hypermethylates and silences the expression of multidrug and toxic compound extrusion 1 (MATE1), a specific pump that expels metformin from the tumor cells by up-regulating DNA methyltransferase 1 (DNMT1). Our findings provide evidence thatKRAS-mutation mCRC patients benefit from metformin treatment and targeting MATE1 may provide a strategy to improve the anticancer response of metformin.

PEAK: A Randomized, Multicenter Phase II Study of Panitumumab Plus Modified Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or Bevacizumab Plus mFOLFOX6 in Patients With Previously Untreated, Unresectable, Wild-Type KRAS Exon 2 Metastatic Colorectal Cancer

2014 ◽  
Vol 32 (21) ◽  
pp. 2240-2247 ◽  
Author(s):  
Lee S. Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Wild Type ◽  
Exon 2 ◽  
Secondary Objective ◽  
Epidermal Growth ◽  
Intent To Treat ◽  
Kras Exon

Purpose To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS. Patients and Methods Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and safety. Results Of 285 randomly assigned patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group, PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P = .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab arms, respectively. Treatment discontinuation rates because of adverse events were similar between arms. Conclusion PFS was similar and OS was improved with panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more clinical benefit with anti–epidermal growth factor receptor therapy.

scholarly journals Cost-Effectiveness of Anti-Epidermal Growth Factor Receptor Therapy Versus Bevacizumab in KRAS Wild-Type (WT), Pan-RAS WT, and Pan-RAS WT Left-Sided Metastatic Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shing Fung Lee ◽  
Horace C. W. Choi ◽  
Sik Kwan Chan ◽  
Ka On Lam ◽  
Victor H. F. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Cost Effectiveness ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Wild Type ◽  
First Line ◽  
Epidermal Growth

ObjectivesWe aimed to compare the economic value of chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) against chemotherapy with bevacizumab (Bev, an anti-vascular endothelial growth factor mAb) as first-line treatment in KRAS wild-type (WT), pan-RAS WT and pan-RAS WT left-sided metastatic colorectal cancer (mCRC) patients from the Hong Kong societal perspective.Materials and MethodsWe developed Markov models and 10-year horizon to estimate costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of chemotherapy plus anti-EGFR therapy against chemotherapy plus Bev in KRAS WT, pan-RAS WT, and pan-RAS WT left-sided mCRC. We considered two times of the local gross domestic product per capita (GDPpc) as the willingness-to-pay (WTP) threshold (2× GDPpc; US$97,832).ResultsAdding anti-EGFR mAb to chemotherapy provides additional 0.24 (95% confidence interval [CI] 0.19–0.29), 0.32 (95% CI 0.27–0.37), and 0.57 (95% CI 0.49–0.63) QALY compared to adding Bev in KRAS WT, pan-RAS WT, and left-sided pan-RAS WT mCRC populations respectively. The corresponding ICER is US$106,847 (95% CI 87,806–134,523), US$88,565 (95% CI 75,678–105,871), US$76,537 (95% CI 67,794–87,917) per QALY gained, respectively.ConclusionsAnti-EGFR therapy is more cost-effective than Bev as a first-line targeted therapy in left-sided pan-RAS WT and pan-RAS WT, with ICER <US$100,000/QALY, compared to KRAS WT mCRC population.

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