Giandomenico Roviello

Surgical management of advanced gastric cancer: An evolving issue

Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer.

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015

This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths.

c-Met targeting in advanced gastric cancer: An open challenge

Despite significant improvements in systemic chemotherapy over the last two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma (GC) remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. High-quality research and advances in technology have contributed to the elucidation of molecular pathways underlying disease progression and have stimulated many clinical studies testing target therapies in an advanced disease setting. In particular, strong preclinical evidence for the aberrant activation of the HGF/c-Met signaling pathways in GC cancers exists. This review will cover the c-Met pathway, the mechanisms of c-Met activation and the different strategies of its inhibition. Next, we will focus on the current state of the art in the clinical evaluation of c-Met-targeted therapies and the description of ongoing randomized trials with the idea that in this disease, high quality translational research to identify and validate biomarkers is a priority task.

CEA and CA19.9 as Early Predictors of Progression in Advanced/Metastatic Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy and Bevacizumab

We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev.

Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer

Metastatic gastric cancer is a lethal disease characterized by a very short overall survival, underlining a critical need of new therapeutic options. Unfortunately, although several molecular targets have been investigated, only very few recently approved agents, such as trastuzumab in the HER2-positive setting and ramucirumab, led to a clinical improvement in the outcome of metastatic gastric cancer patients. VEGF (vascular endothelial growth factor) is one of the most potent angiogenic factors and is a signalling molecule secreted by many solid tumours. Since high VEGF expression is one of the characteristic features of gastric carcinomas, targeting VEGF is therefore considered as a promising therapeutic strategy for gastric cancer. In the scenario of possible new target therapies with particular regard to angiogenesis, apatinib is a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2. It is an orally-bioavailable agent currently being studied in several solid tumour types showing a promising activity in gastric cancer. Due to the recent positive results as a third line of treatment for metastatic gastric cancer patients, apatinib may be an interesting and novel type of targeted treatment for metastatic gastric cancer in several lines of therapy. In this review, we summarize the available data of apatinib, mainly focused on the clinical aspect, in advanced/metastatic gastric cancer.

No clear evidence of a clinical benefit of a sequential therapy regimen with abiraterone acetate and enzalutamide

Prostate cancer is the second leading cause of cancer-related deaths in men in most western countries. New agents for metastatic castration-resistant prostate cancer (CRPC) developed in the past 3 years include abiraterone acetate (AA) and enzalutamide (ENZ), which inhibit signaling by and synthesis of androgens, respectively. Because they share the same target, potential clinical cross-resistance between AA and E is possible. In this review, we discuss the results of clinical studies in which CRPC patients were treated with AA and E either separately or in sequence after first-line treatment with docetaxel. Our review suggests that sequential administration of AA and E in either order has limited activity after docetaxel therapy. Prospective studies that further examine sequential treatments with AA and E are warranted.

Bevacizumab and Weekly Docetaxel in Patients with Metastatic Castrate-Resistant Prostate Cancer Previously Exposed to Docetaxel

Background. The aim of this paper was to evaluate the activity and tolerability of docetaxel (D) and bevacizumab (Bev) in patients with metastatic castrate-resistant prostate cancer (CRPC) previously exposed to D. Methods. Treatment consisted of D 30 mg/m2 i.v. for four consecutive weekly administrations followed by a 2-week rest interval, in addition to Bev 5 mg/kg i.v. every 2 weeks. Results. Forty-three patients were enrolled: a PSA response was observed in 27 patients (62.7%, 95% CI: 0.41 to 0.91), and a palliative response was achieved in 31 patients (72.1%, 95%CI: 0.48 to 1.02). After a median followup of 11.3 months, only five patients had died. The regimen was generally well tolerated. Conclusion. Weekly D + biweekly Bev seems to be an effective and well-tolerated treatment option for patients with metastatic CRPC previously exposed to D-based chemotherapy.

Meta‐analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer

Several associations between microsatellite instability (MSI) and other clinicopathological factors have been reported in gastric cancer, but the results have been ambiguous. This systematic review and meta‐analysis investigated the relationship between MSI and overall survival and clinicopathological characteristics of patients with gastric cancer.

The third line of treatment for metastatic prostate cancer patients: Option or strategy?

New agents for metastatic castration-resistant prostate cancer (CRPC) developed in the past 3 years include cabaziataxel (Cbz), abiraterone acetate (AA) and enzalutamide (E). In this review, the results of clinical studies in which one of these drugs is included as the third line of treatment are discussed. Our review suggests that AA and E have limited activity, while Cbz seems to retain its efficacy. Prospective studies that further examine sequential treatments are warranted.

Angiogenesis inhibitors in gastric and gastroesophageal junction cancer

Despite significant improvements in systemic chemotherapy during the past two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. Unfortunately, although a number of molecular targets have been studied, very few of these agents can be used in a clinical setting. In this review, we summarize the available data on anti-angiogenic agents in advanced/metastatic gastric cancer.