Antibiotic prophylaxis for skin toxicity induced by antiepidermal growth factor receptor agents: a systematic review and meta-analysis.

Topical and systemic prophylactic measures, which are administered before the development of epidermal growth factor receptor (EGFR)-related acneiform rash, are appropriate interventions to mitigate the intensity of skin toxicity. We have performed a systematic review and meta-analysis to evaluate whether prophylactic antibiotics may reduce the occurrence and severity of anti-EGFR drug-related skin rashes. A systematic review was performed by searching Medline, Scopus, Embase, CINAHL, LILACS, Web of Science and the Cochrane Library from inception until March 2016 for publications regarding the pre-emptive role of antibiotics for EGFR-induced skin rashes. Fixed- or random-effects meta-analyses, according to heterogeneity, were used to summarize odds ratios of skin toxicity with antibiotic use. Of the 827 citations found in the search, 13 studies comprising 1073 patients were included in the analysis. In 12 studies, patients in the prophylactic antibiotic arms had a lower risk of developing a skin rash (odds ratio 0·53, 95% confidence interval 0·39-0·72, P < 0·01) than patients without antibiotic prophylaxis. In particular, moderate-to-severe toxicities (grades 2-4) were reduced by nearly two-thirds (odds ratio 0·36, 95% confidence interval 0·22-0·60, P < 0·01) in 13 studies. This translated to a 26% absolute difference of high-grade skin rash compared with the control arms (from 50% to 24%). The results of this meta-analysis show that the risk of skin rash after treatment with anti-EGFR agents for solid tumours was significantly lower in patients taking prophylaxis with antibiotics than in those who were not. Therefore, taking pre-emptive tetracyclines for several weeks at the start of anti-EGFR treatment can significantly reduce the incidence and severity of cutaneous acneiform rash.

Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype.

Triple negative breast cancer (TNBC) represents the 15-20% of all breast cancers (BC) and is characterized by a very aggressive behavior. Recent data suggest that TNBC is not a single disease, but it is rather an umbrella for different ontology-profiles such as basal like 1 and 2, mesenchymal, and the luminal androgen receptor (LAR). The LAR subtype is characterized by the expression of the Androgen Receptor (AR) and its downstream effects. Notwithstanding the role of the AR in several signaling pathways, its impact on a biological and clinical standpoint is still controversial. The LAR subtype has been associated with better prognosis, less chemotherapy responsiveness and lower pathologic complete response after neoadjuvant treatment. Clinical evidence suggests a role for anti-androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering an interesting chemo-free alternative for chemo-unresponsive patients, and therefore potentially shifting current treatment strategies.

Tumour Budding and Survival in Stage II Colorectal Cancer: a Systematic Review and Pooled Analysis.

PURPOSE: Tumour budding is defined as the presence of isolated or small clusters of malignant cells at the invasive edge of the tumour. It is considered a negative prognostic factor in colorectal cancer (CRC) and is associated with a poor outcome and adverse pathological features. Here, we report a meta-analysis of the association of tumour budding and survival in stage II CRC patients. METHODS: PubMed, EMBASE, Web of Science and SCOPUS were searched for studies that assessed the relationship between tumour budding and 5-year overall survival (OS) in stage II CRC patients. Published data were extracted and used to compute odds ratios (ORs) for death at 5 years and hazard ratios (HRs) for survival amongst patients with respect to the extent of tumour budding, using multivariate analysis. Data were pooled using the Mantel-Haenszel random effect model. RESULTS: We analysed 12 studies that included a total of 1652 patients. High-grade budding was associated with worse OS at 5 years (OR for death, 6.25; 95 % confidence interval [CI], 4.04-9.67; P < 0.00001). The absolute difference in 5-year OS was -25 % (95 % CI, -18- - 33 %, P < 0.00001). It was particularly noteworthy that the presence of high-grade budding was associated with an increased risk of death (HR for death, 3.68; 95 % CI, 2.16-6.28, P < 0.00001). CONCLUSIONS: Tumour budding is associated with worse survival in stage II CRC, in particular in pT3N0M0 patients. It could therefore potentially be used when deciding whether to administer adjuvant chemotherapy in high-risk node negative CRC patients.

Oxaliplatin-based chemotherapy: a new option in advanced hepatocellular carcinoma. a systematic review and pooled analysis.

Advanced hepatocellular carcinoma (HCC), for which locoregional treatment is not an option, is a candidate for palliative systemic therapy, but an accepted chemotherapy regimen does not exist. We have conducted a systematic literature review and meta-analyses to quantify the benefits of oxaliplatin (OXA)-based chemotherapy in advanced HCC in patients not exposed to sorafenib. Studies that enrolled advanced HCC patients treated with first-line OXA-based chemotherapy were identified using PubMed, Web of Science, SCOPUS, The Cochrane Register of Controlled Trials and EMBASE. A systematic review was conducted to calculate the pooled response rate and 95% confidence interval. The pooled median progression-free survival (PFS) and overall survival, weighted on the number of patients of each selected trials, were also calculated. We tested for significant heterogeneity by Cochran's chi-squared test and I-square index. Thirteen studies were included in this review, with a total of 800 patients analysed. The pooled response rate was 16.8%. The median PFS and overall survival were 4.2 and 9.3 months, respectively, with a 1 year overall survival of 37%. The weighted median PFS/overall survival and response rate were 4.5/11 months and 20% in Western patients. Conversely, in Asiatic studies, the median PFS/overall survival and response rate were 2.43/6.47 months and 13.2%, respectively. OXA-based chemotherapy is effective in advanced HCC and represents a viable option in these patients. A head to head comparison with sorafenib or a second-line agent should be verified in prospective trials.