Retrospective Study of Regorafenib Versus TAS-102 Efficacy and Safety in Chemorefractory Metastatic Colorectal Cancer (mCRC) Patients: A Multi-institution Real Life Clinical Data

INTRODUCTION: There have been significant developments in colorectal cancer (CRC) research over the last few years, with the introduction of new agents that have been prolonged median overall survival of metastatic colorectal cancer (mCRC). These therapies have improved patient outcomes; however, despite significant progress in strategies for cancer treatment, their use is limited by development of resistant mechanism. Almost 30% of patients with refractory mCRC will remain good candidates for further treatment. Regorafenib and TAS-102 are novel antitumor agents for patients with refractory mCRC. However, it is unclear which patients may derive a survival benefit from these drugs in real-life clinical practice.; METHODS: We performed a retrospective analysis evaluating safety and efficacy of TAS-102 and regorafenib in a cohort of refractory mCRC patients, in 3 different centers between January 1 2018 and May 31 2020, with the aim of assessing the optimal sequence treatment for these 2 drugs.; RESULTS: One hundred and forty mCRC patients were included in the analysis. Of these patients, 64 received regorafenib and 76 received TAS-102 as first treatment. After progression, in the regorafenib 24 (37%) patients switched to secondary treatment with TAS-102, instead, in the TAS-102 group, among 76 patients, 29 (45%) patients switched to secondary treatment with regorafenib. Disease control was achieved in 8 (12.5%) of 64 patients in the regorafenib group and 17 (22.4%) of 76 patients in the TAS-102 group. In terms of efficacy, the PFS and OS were similar in both treatment groups for primary and secondary treatments. AEs reported in this analysis were mostly consistent with the known safety profiles of regorafenib and TAS-102 in previous clinical trials.; CONCLUSION: The present study is the first one to compare the activity of the two agents in a large cohort of chemo-refractory mCRC patients providing more details about the best sequence, to be incorporated in clinical practice. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved

Prevention of regorafenib related skin toxicity in refractory metastatic colorectal cancer (mCRC) patients (pts): a single institution experience

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axl has a prognostic role in metastatic colorectal cancer mcrc and is a predictive biomarker of lack of efficacy of chemotherapy ct cetuximab in ras wild type wt patients pts

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Diagnostic value/performance of radiological liver imaging during chemoterapy for gastrointestinal malignancy: A critical review

This article reviews the main toxic effect, complications and relative imaging findings of the liver that may appear during the oncologic follow up among patients affected by gastrointestinal malignancy. Awareness of the causative chemotherapeutic agent and regimens, pathophysiology and relative characteristic imaging findings of hepatic injuries is critical in order to obtain an accurate diagnosis especially when these parenchymal lesions are focal. An accurate synergic radiological diagnosis with Computed Tomography (CT) and Magnetic Resonance (MR) techniques may induce a potential termination of ineffective/toxic chemotherapy during early phases of treatment, changing the therapeutic plan in order to avoid first unnecessary liver biopsy and then invasive treatment as hepatic resection if not required

The acquired resistance to the combination of the anti-EGFR cetuximab and the MEK-inhibitor refametinib in KRAS mutated colorectal cancer cell lines depends on PI3K-signalling

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Applicazione di un protocollo multidisciplinare per la patologia da mobbing

This study proposes a method for assessing mobbing in the clinical setting. We present 187 outpatients (79 males, 108 females; mean age: 41 years) who asked medical assistance, during the last five years, for psychopathological problems by them ascribed to mobbing in the working environment. Fortyeight subjects were employed in public institutions, 139 in private companies. All patients underwent occupational health visit, psychological counselling (including personality tests administration), and psychiatric evaluation. A clinical picture probably due to mobbing was diagnosed in 31 workers (17% of the cases): 2 cases of Post-Traumatic Stress Disorder (PTSD), 27 of Adjustment Disorder (AD), and 2 of anxiety disorder. Four cases of AD were work-related but not due to mobbing. In 7 patients the correlation with the working activity was possible but difficult to demonstrate, due to concomitant (non-occupational) stressing situations. A pre-existing psychiatric disorder was identified in 74 subjects (40%). Altered interpersonal relationships with the colleagues were present in 62 cases (33%). Nine patients did not complete the diagnostic protocol. In conclusion, a pure mobbing syndrome was diagnosed in a lower proportion than that reported by other investigators. This difference probably depends on patients preselection criteria. The described interdisciplinary approach appears useful for the diagnostic assessment of suspect mobbing cases, that in turn is crucial for prognosis and treatment, as well as in relation to medico-legal issues and work-related compensation claims

Retrospective Study of Regorafenib Versus TAS-102 Efficacy and Safety in Chemorefractory Metastatic Colorectal Cancer (mCRC) Patients: A Multi-institution Real Life Clinical Data

Introduction: There have been significant developments in colorectal cancer (CRC) research over the last few years, with the introduction of new agents that have been prolonged median overall survival of metastatic colorectal cancer (mCRC). These therapies have improved patient outcomes; however, despite significant progress in strategies for cancer treatment, their use is limited by development of resistant mechanism. Almost 30% of patients with refractory mCRC will remain good candidates for further treatment. Regorafenib and TAS-102 are novel antitumor agents for patients with refractory mCRC. However, it is unclear which patients may derive a survival benefit from these drugs in real-life clinical practice. Methods: We performed a retrospective analysis evaluating safety and efficacy of TAS-102 and regorafenib in a cohort of refractory mCRC patients, in 3 different centers between January 1 2018 and May 31 2020, with the aim of assessing the optimal sequence treatment for these 2 drugs. Results: One hundred and forty mCRC patients were included in the analysis. Of these patients, 64 received regorafenib and 76 received TAS-102 as first treatment. After progression, in the regorafenib 24 (37%) patients switched to secondary treatment with TAS-102, instead, in the TAS-102 group, among 76 patients, 29 (45%) patients switched to secondary treatment with regorafenib. Disease control was achieved in 8 (12.5%) of 64 patients in the regorafenib group and 17 (22.4%) of 76 patients in the TAS-102 group. In terms of efficacy, the PFS and OS were similar in both treatment groups for primary and secondary treatments. AEs reported in this analysis were mostly consistent with the known safety profiles of regorafenib and TAS-102 in previous clinical trials. Conclusion: The present study is the first one to compare the activity of the two agents in a large cohort of chemo-refractory mCRC patients providing more details about the best sequence, to be incorporated in clinical practice

A case report of a severe fluoropyrimidine-related toxicity due to an uncommon DPYD variant

Introduction: Fluoropyrimidines such as 5-fluorouracil (5-FU) and its orally active prodrug, capecitabine, are widely used in the treatment of gastrointestinal cancer, including colorectal cancer. Dihydropyrimidine dehydrogenase (DPD) plays an important role in the 5-FU metabolism. Dihydropyrimidine dehydrogenase gene (DPYD) is a highly polymorphic gene with several hundreds of reported genetic variants and DPD activity levels vary considerably among individuals, with different 5-FU-related efficacy and toxicity. About 5% of the population is deficient in DPD enzyme activity. The most well studied DPYD variant is the IVS14+1G>A, also known as DPYD ∗2A. In this report, we present a case of a patient with a double heterozygote DPYD variant (DPYD activity score: 0,5 according to Clinical Pharmacogenetics Implementation Consortium) who experienced a severe fluoropyrimidine-related toxicity resolved without any consequence. Patient concerns: A 46-years-old Caucasian man with diagnosis of left colon adenocarcinoma underwent left hemicolectomy on July 2017: pT3 G3 N1c M0. According to the disease stage, he started an adjuvant therapy with XELOX using capecitabine at 50% of total dose, because of his DPYD IVS14+1G>A variant, detected before the treatment. DIAGNOSIS: After few days, despite of this dose reduction, he experienced life-threatening adverse events such as mucositis G3, diarrhea G3, neutropenia G4, thrombocytopenia G4, and hyperbilirubinemia G3 according to Common Terminology Criteria for Adverse Events v 5.0. Interventions: As first, we set up an intensive rehydration therapy, antibiotic and antifungal prophylaxis, Granulocyte-Colony Stimulating Factors, and supportive blood transfusions. Additional genetic tests revealed a double heterozygote variant of DPYD gene (DPYD IVS14+1G>A and 2846A>T) which is a very rare situation and only 3 cases are described in literature, all of them concluded with patient’s death. Outcomes: After 3 weeks of intensive therapy, the patient was fully recovered. Furthermore, all the whole-body CT scans performed since discharge from the hospital until now, have confirmed no evidence of disease. Conclusions: Recent studies demonstrated that screening strategy for the most common DPYD variants allowed for avoiding toxicities and saving money. This report underlines the importance of genotyping DPYD before treatment and emphasizes the role of genotype-guided dose individualization. Abbreviations: 5,10-MTHF = 5,10-Methylenetetrahydrofolate, 5-FU = 5-fluorouracil, AEs = Adverse events, CDA = cytidinedeaminase, CES = carboxylesterase, CPIC = Clinical Pharmacogenetics Implementation Consortium, CRC = colorectal cancer, CT = computed tomography, CTCAE = Common Terminology Criteria for Adverse Events, DPD = dihydropyrimidine dehydrogenase, DPYD = dihydropyrimidine dehydrogenase gene, DPYD-AS = DPYD activity score, ECOG = Eastern Cooperative Oncology Group, EDTA = ethylenediaminetetraacetic acid, FdUMP = 5-fluoro-20-deoxyuridine-50-monophosphate, HFS = hand-foot syndrome, HGB = hemoglobin, INB = incremental net benefit, INR = International Normalized Ratio, mCRC = metastatic colorectal cancer, MTHFR = Methylene Tetrahydrofolate Reductase, NEU = Neutrophils, PCR = polymerase chain reaction, PLT = Platelets, SNPs = single-nucleotide polymorphisms, TSER = thymidylate synthase enhancer region, TYMP = thymidine phosphorylase, TYMS = thymidylate synthase, VNTR = variable number of tandem repeat, WBC = white blood cells