Hepatocellular Carcinoma: Review of Targeted and Immune Therapies.

BACKGROUND: Hepatocellular carcinoma is the fifth most common cancer globally and the second leading cause of cancer-related mortality worldwide. Despite the established efficacy of screening programs for at-risk individuals, most patients are diagnosed at later stages of disease, wherein the tumor characteristics or liver disease progressions do not allow for curative interventions. Many cytotoxic chemotherapeutic agents have been tested in patients with advanced disease with disappointing outcomes and poor tolerance; therefore, no standard systemic therapy emerged until the approval of sorafenib in 2006. CONCLUSION: Despite the toxicity and low response rate, sorafenib had shown a significant survival benefit in phase III clinical trials, thus encouraging clinical research aimed at advancing the field of molecular therapy. Disrupted signaling pathways related to hepatocellular carcinoma (HCC) include the Wnt/ß-catenin, Ras/Raf/MAPK, phosphatidyl inositol 3-kinase/Akt/mechanistic target of rapamycin, hepatocyte growth factor/c-mesenchymal-epithelial transition, IGF, vascular endothelial growth factor, and platelet-derived growth factor pathways, and a variety of agents targeting these pathways are currently under investigation. Additionally, better comprehension of the complex mechanisms underlying the ability of tumor cells to escape immune surveillance has led to impressive results with immunotherapy in many types of cancer, and this treatment strategy is currently being developed for HCC patients. Previous and ongoing targeted therapy and immunotherapy trials for HCC are discussed in this review.

The effects of palliative chemotherapy in metastatic colorectal cancer patients with an ECOG performance status of 3 and 4.

BACKGROUND: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials. Our objectives were to compare the survival and safety of ECOG PS 3/4 patients who were administered chemotherapy with those who received BSC only. PATIENTS AND METHODS: We retrospectively analyzed all consecutive mCRC patients who started first-line chemotherapy at our institution in a 4-year period. A multivariable Cox regression model was used to adjust for prognostic factors and logistic regression, to identify predictive factors of Grade 3/4 toxicity. RESULTS: From June 2008 to June 2012, 240 consecutive patients were included: 100 (41.7%) had an ECOG PS of 0/1, 75 (31.3%) ECOG PS of 2, and 65 (27%) ECOG PS of 3/4. Median survival for patients treated with chemotherapy was 18.4 months for patients with ECOG PS of 0/1, 10.8 months for those with ECOG PS of 2, and 6.8 months for patients with ECOG PS of 3/4. Among those with ECOG PS of 3/4, chemotherapy use led to a nonsignificant survival gain (median, 6.8 vs. 2.3 months for BSC; P = .13). Factors significantly associated with worse survival in an adjusted analysis were right-sided tumors (hazard ratio [HR], 2.97; P = .005) and ECOG PS status (ECOG PS 2 vs. 0/1; HR, 1.67; P = .025, and ECOG PS 3/4 vs. 0/1; HR, 2.67; P < .0001). The rate of Grade ≥ 3 toxicities during the first cycle did not differ significantly across ECOG groups; likely because 40% of ECOG PS 3/4 patients received upfront dose-reduced therapy. The rates of treatment-related hospitalization were similar across all ECOG groups. All deaths were disease-associated. CONCLUSION: Our retrospective study suggests that chemotherapy might benefit selected mCRC patients with poor PS. With up-front dose reduction and close monitoring for toxicity, the risk of serious adverse events is minimized.

Primary prevention of colorectal cancer: myth or reality?

Colorectal cancer incidence has been rising strongly in parallel with economic development. In the past few decades, much has been learned about the lifestyle, dietary and medication risk factors for this malignancy. With respect to lifestyle, compelling evidence indicates that prevention of weight gain and maintenance of a reasonable level of physical activity can positively influence in lowering the risk. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. Though quite often recommended, the role for many supplements, including omega-3, vitamin D, folate, and vitamin B6, remains unsettled. Only calcium and vitamin D supplementation appear to add a modest benefit, particularly in those with a low daily intake. With regard to chemoprevention, medications such as aspirin and nonsteroidal anti-inflammatory drugs, and postmenopausal hormonal replacement for women might be associated with substantial reductions in colorectal cancer risk, though their utility is affected by their side effect profile. However, the role of agents such as statins, bisphosphonates and antioxidants have yet to be determined. Ultimately, primary prevention strategies focusing on modifying environmental, lifestyle risk factors, and chemopreventive drugs are options that have already been tested, and may impact on colon cancer incidence.

Percutaneous transhepatic biliary drainage in patients with advanced solid malignancies: prognostic factors and clinical outcomes.

PURPOSE: Obstructive jaundice (OJ) is a cumbersome complication in late-stage malignancies, and percutaneous transhepatic biliary drainage (PTBD) is often used to relieve symptoms and allow chemotherapy (CT). METHODS: From July 2008 to August 2011, 71 patients (pts) with OJ due to solid malignancies underwent PTBD in our institution. Baseline characteristics, procedure complications, and outcomes were retrospectively collected. The primary objective was to estimate overall survival (OS) after PTBD. RESULTS: Median age was 60 years, 63% had an ECOG performance status (PS) of 1-2, and 10% were receiving supportive care (SC). Most had primary gastrointestinal tumors (89%) and metastatic disease at diagnosis (59%). Mean hospital stay was 16.6 days (2-90 days), with bilirubin value decreased (BVD) after 80% of procedures. Cholangitis was observed in 66.2% of pts and 60.6% required readmissions. Only 51.6% of pts not in SC were eligible for CT after PTBD. Median OS was 2.9 months (95% CI 0.62-5.2). Prognostic factors on univariate analysis include ECOG ≤2 (6.8 versus 0.79 months, p < 0.0001), BVD (6.7 versus 0.33 months, p < 0.0001), and CT after PTBD (13.7 versus 1.2 months p < 0.0001). On multivariate analysis, CT after procedure was related to better OS (HR 0.15, CI 0.06-0.38, p < 0.001). CONCLUSIONS: Malignant OJ is a late event in cancer pts. Thorough evaluation is needed before determining eligibility to PTBD due to its high complication and hospitalization rates. In the current analysis, pts with PS >2 and who are not candidates for further CT had a dismal prognosis and should probably not be offered PTBD.