Gastric cancer is one of the most common types of cancer in the world, usually diagnosed at an advanced stage. Despite the advances in specific anticancer agents' development, the survival rates remain modest, even in early stages. In 15%-20% of cases, the human epidermal growth factor receptor 2 (HER2) overexpression was identified. We conducted a general review to summarize the progress that has been made in the targeted treatment of HER2-positive esogastric junction or gastric adenocarcinoma. According to our findings, trastuzumab is the only validated anti-HER2 agent in locally advanced or metastatic disease and its adjuvant effectiveness is assessed in a RTOG phase III study. In a previously treated advanced disease, the maytansine derivate TDM 1 failed to be approved as a second-line regimen, and the tyrosine kinase inhibitor, lapatinib, shows modest results. The antiangiogenics have not been analyzed in specific populations and targeting the mesenchymal-epithelial transition factor (MET) receptor, overexpressed in up to 46% of the advanced disease, seems encouraging. Regarding the checkpoint inhibitors, based on KEYNOTE 059 multilevel ongoing trial, stratified according to the HER2 and programmed death-ligand (PD-L) 1 status, pembrolizumab was approved for third-line treatment of gastric or gastroesophageal junction adenocarcinoma.
Cervical cancer represents a general health issue spread all over the globe, which prompts the surge of scientific survey toward the rise of survival and condition of life of these patients. American and European guidelines suggest the open surgery, laparoscopic, and robotic surgery are the main therapeutic approaches for radical hysterectomy for patients with cervical cancer. This is the first survey to analyze the long-term oncological outcome of an extensive series of subjects cared for with multimodality treatment, here comprising robotic surgery. This study intents to evaluate the long-term oncological result in patients diagnosed with cervical cancer treated with radiotherapy (±chemotherapy) and robotic surgery compared with open surgery. Medical files of 56 patients diagnosed with cervical cancer who underwent a robotic hysterectomy and radiotherapy ± chemotherapy were retrospectively analyzed. The median age at diagnosis was 50.5 (range: 23–70). Eleven patients (19.6%) presented in an early stage (IB–IIA) and 80.4% advanced stage (IIB–IVA). Overall response rate after radiotherapy and chemoradiotherapy was 96.2%. Pathologic complete response was obtained in 64% of patients. After a median follow-up of 60 months (range: 6–105 months), 8 patients (14.2%) presented local recurrence or distant metastases. Disease-free survival (DFS) was 92% at 2 years and 84% at 3 and 5 years. Overall survival (OS) rates at 2, 3, and 5 years for patients with robotic surgery were 91%, 78%, and 73%, median OS not reached. OS was lower in the arm of open surgery (2, 3, and 5 years 87%, 71%, and 61%, respectively; median OS was 72 months P = .054). The multivariate analysis regarding the outcome of patients revealed an advantage for complete versus partial response ( P < .002), for early versus advanced stages ( P = .014) and a 10% gained in DFS at 3 years for patients in whom chemoradiotherapy was administered (DFS at 3 years 75% vs 85%) in patients with advanced stages. Robotic surgery has a favorable oncological outcome when associated with multimodal therapy.
Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients’ daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient’s daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma.
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