The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions.

The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.

Nephrotoxicity in cancer treatment: An overview.

Anticancer drug nephrotoxicity is an important and increasing adverse drug event that limits the efficacy of cancer treatment. The kidney is an important elimination pathway for many antineoplastic drugs and their metabolites, which occurs by glomerular filtration and tubular secretion. Chemotherapeutic agents, both conventional cytotoxic agents and molecularly targeted agents, can affect any segment of the nephron including its microvasculature, leading to many clinical manifestations such as proteinuria, hypertension, electrolyte disturbances, glomerulopathy, acute and chronic interstitial nephritis, acute kidney injury and at times chronic kidney disease. The clinician should be alert to recognize several factors that may maximize renal dysfunction and contribute to the increased incidence of nephrotoxicity associated with these drugs, such as intravascular volume depletion, the associated use of nonchemotherapeutic nephrotoxic drugs (analgesics, antibiotics, proton pump inhibitors, and bone-targeted therapies), radiographic ionic contrast media or radiation therapy, urinary tract obstruction, and intrinsic renal disease. Identification of patients at higher risk for nephrotoxicity may allow the prevention or at least reduction in the development and severity of this adverse effect. Therefore, the aim of this brief review is to provide currently available evidences on oncologic drug-related nephrotoxicity.

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018).

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.

Dual inhibiting EGFR and VEGF pathways versus EGFR-TKIs alone in the treatment of advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: The strategy of dual inhibiting epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways has been extensively investigated in advanced non-small-cell lung cancer (NSCLC), but the benefit-to-risk ratio of dual-targeted regimen versus EGFR-tyrosine kinase inhibitors (TKIs) alone is still unclear. We thus perform this meta-analysis to assess the efficacy and safety of this regimen versus EGFR-TKIs alone in those patients. METHODS: Databases from PubMed, Web of Science and the Cochrane Library up to March 31, 2015 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials (RCTs) evaluating dual inhibiting EGFR and VEGF pathways versus EGFR-TKIs alone in advanced NSCLC. The endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and grade 3 or 4 adverse events. Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 1918 patients with advanced NSCLC from 4 RCTs were identified for the analysis. The pooled results demonstrated that dual inhibiting EGFR and VEGF pathways significantly improved the PFS (HR 0.71, 95 % CI 0.58-0.86, p < 0.001) and ORR (OR 1.54, 95 % CI 1.14-2.08, p = 0.005) in unselected NSCLC when compared to EGFR-TKIs alone, but it did not translate into OS benefit (HR 0.94, 95 % CI 0.84-1.05, p = 0.24). No evidence of publication bias was observed. CONCLUSIONS: Our study suggests that dual inhibition of EGFR and VEGF pathways significantly improves PFS and ORR, but it does not translate into survival benefit in unselected NSCLC patients. Prospective clinical trials investigating the role of this regimen in EGFR mutation-positive NSCLC are still warranted.

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer 2015.

Colorectal cancer (CRC) is the second leading cause of cancer dead in Spain. About half the patients will eventually develop distant metastases. However, as treatment options are expanding, prognosis has steadily improved over the last decades. Management of advanced CRC should be discussed within an experienced multidisciplinary team to select the most appropriate systemic treatment (chemotherapy and targeted agents) and to integrate surgical or ablative procedures when indicated. Disease site and extent, resectability, tumor biology and gene mutations, clinical presentation, patient preferences, and comorbidities are key factors to design a customized treatment plan. The aim of these guidelines is to provide synthetic recommendations for managing advanced CRC patients.

Assessment of folate receptor-α and epidermal growth factor receptor expression in pemetrexed-treated non-small-cell lung cancer patients.

INTRODUCTION: Folate receptor-α regulates cellular uptake of folates and antifolates (eg, pemetrexed) and is frequently expressed in pulmonary adenocarcinoma. EGFR is an established therapeutic target in NSCLC. Therapies targeting FRA or EGFR are available. The association between FRA and EGFR expression in advanced NSCLC has not been explored. Combining therapeutic FRA antibodies with an EGFR inhibitor might be beneficial, if both of the targets are significantly coexpressed. PATIENTS AND METHODS: Specimens from 160 advanced NSCLC patients receiving pemetrexed-based chemotherapy were assessed for membranous FRA and EGFR protein expression using immunohistochemistry and the Hybrid (H)-score. EGFR (exons 18-21) and Kirsten RNA-associated rat sarcoma 2 virus (exon 2) mutations were determined. Results were correlated to patients' clinicopathological data, progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-seven patients (29%) had tumors with strong FRA and EGFR expression, but no statistically significant correlation was seen between protein levels of FRA and EGFR. High membranous FRA expression (H-score ≥ 20) was associated with prolonged PFS (5.5 vs. 3.4 months; hazard ratio [HR], 0.6060; P = .0254) and improved OS (12.1 vs. 6.4 months; HR, 0.5726; P = .0076). CONCLUSION: Survival times are improved in NSCLC patients whose tumors show strong membranous FRA expression. No statistical correlation between membranous FRA and EGFR expression was demonstrated in advanced NSCLC, but 47 patients (29%) had higher expression of both of the receptors and could be suitable for combined targeted therapies.

Challenges in first line chemotherapy and targeted therapy in advanced gastric cancer.

Chemotherapy prolongs survival in advanced gastric cancer (AGC). The challenges involved in this procedure are providing a framework to aid in determining the best single or combined chemotherapy protocols for targeted agents in front-line therapy for patients in a clinical setting. A review of Phase II-III studies published or referenced in major oncology congress publications from 1970 to 2013 was performed. Cisplatin and fluoropyrimidine remain the reference regimen. Fluoropyrimidine combined with oxaliplatin or irinotecan may also be employed in special situations. There are no comparative studies of the same regimens with or without anthacyclines; thus, the effectiveness of anthacyclines remains under debate. The introduction of trastuzumab in the front-line therapy of HER2-positive patients and ramucirumab in refractory patients ushered in an age of targeted therapy for this disease.