We performed a systematic review and meta-analysis of the risk of gastrointestinal (GI) toxicities associated with MEK inhibitors. Eligible studies included randomized Phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of stomatitis, diarrhea and vomiting. Our search strategy yielded 250 potentially relevant citations from Pubmed/Medline, Google scholar and CENTRAL Cochrane registry. After exclusion of ineligible studies, a total of 16 clinical trials were considered eligible for the meta-analysis. The relative risks of all-grade stomatitis, diarrhea and vomiting were 2.03 (95% CI 1.41-2.96; p = 0.002), 1.92 (95% CI 1.48-2.50; p < 0.00001) and 1.35 (95% CI 1.06-1.71; p = 0.01). Subgroup analyses according to agent used (trametinib vs Selumetinib), the regimen used (monotherapy vs combination) and the cancer treated (melanoma vs nonmelanoma) did not reveal any significant difference between the subgroups. Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of stomatitis, diarrhea and vomiting compared to control. Clinicians should be aware of this risk and perform regular assessment.

Recent trials have suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced non-small-cell lung cancer (NSCLC). However, physicians have little guidance on selecting which patients benefit the most and what drug or regimen is optimal. Here, we report a systematic review and network meta-analysis of maintenance treatments in subgroups determined by performance status (PS), epidermal growth factor receptor (EGFR) mutation, histology and response to induction.

Anthracyclines play a broad and important role in the care of patients with either operable or metastatic breast cancer. However cardiotoxicity narrows the therapeutic index of this drug class leading to potentially clinically meaningful treatment delays or discontinuations. We conducted a Bayesian network meta-analysis, a validated statistical methodology, allowing direct and indirect comparison of cardiotoxicity of different anthracycline and non-anthracycline regimens.

Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a tolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was to assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and tremelimumab).

Several reports suggest that gemcitabine (GEM) plus S-1 combination (GS) is associated to prolong the survival in patients with unresectable pancreatic cancer (PC). We conducted a systemic review and meta-analysis of studies comparing the safety and efficacy of GS versus GEM.Summary data from randomized trials and retrospective studies were searched in PubMed, EMBASE, Web of Science, and the Cochrane Library. Statistical analyses were conducted to calculate the hazard ratios (HRs) and relative risk (RR) with 95% confidence intervals (CIs) using random-effects models. Subgroup analyses based on the chemotherapy cycles were performed to explore the efficacy and toxicity for therapy. Sensitivity analyses were conducted by removing specific studies to assess the effects of study quality.Between January 2004 and August 2012, 4 RCTs and 2 retrospective studies including a total of 1025 cases were identified. The overall survival (OS) (HR: 0.82; 95% CI, 0.70-0.96; P = 0.01) and progression-free survival (PFS) (HR: 0.65; 95% CI, 0.55-0.77; P < 0.001) for the GS arm were significantly longer than the GEM arm. The differences in objective response rate (ORR) (RR: 1.24; 95% CI, 1.17-1.33; P < 0.001) and disease control rate (DCR) were also better in the GS arm (RR: 1.37; 95% CI, 1.19-1.59; P < 0.001). Grades 3 to 4 toxicities in both the groups were similar except neutropenia and diarrhea, which were more frequent in the GS arm (P < 0.001). In the subgroup analysis, the cycle for chemotherapy every 4 weeks has equivalent efficacy and less toxicity than regimens every 3 weeks in the GS arm.The current meta-analysis suggested that GEM significantly prolonged OS and PFS when added to S-1 combination in patients with unresectable PC. GS therapy also offers better ORR and DCR than GEM monotherapy and no unexpected toxicity was evident.

Aflibercept is an engineered humanized vascular endothelial growth factor (VEGF)-targeted agent. Severe infections are serious adverse event associated with aflibercept. However, the contribution of aflibercept to infection is still unknown. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing severe infections in cancer patients treated with aflibercept.

To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.

Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still first- line chemotherapy. However gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.

We performed a systematic review and meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with ramucirumab.

Adult ovarian sex cord-stromal tumors (SCSTs) are a rare histological subtype of ovarian cancer associated with a favorable prognosis. Bleomycin-containing regimens are standards of care, although pneumonitis may cause potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of bleomycin in SCST treatment.

Emergence of new agents has deeply modified treatment options and the role of chlorambucil (CLB) in B-cell malignancies. We conducted a systematic review of prospective, randomized, controlled trials (RCTs) investigating the benefits and harms of CLB used alone or in combination with other treatment in patients suffering from chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) or Waldenström macroglobulinemia (WM). For CLL, review of the nine RCTs showed that the main advantage of CLB is its low toxicity in comparison with purine nucleoside analogs like fludarabine in either CLL or NHL. In CLL, the major disadvantage is the very low rate of complete response, except when combining an anti-CD20 antibody. For B-cell lymphoma and WM, six RCTs were summarized. Results according to the usual criteria are presented and the role of CLB, used mostly in combination with an anti-CD20 antibody, is discussed for each indication, in particular for unfit patients.

This is an updated version of a review first published in theCochrane Database of Systematic Reviews, Issue 4, in 2011. Vulval intraepithelial neoplasia (VIN) is a pre-cancerous condition of the vulval skin and its incidence is increasing in women under 50 years. High-grade VIN (also called usual-type VIN (uVIN) or VIN 2/3 or high-grade vulval intraepithelial lesion) is associated with human papilloma virus (HPV) infection and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of high-grade VIN; and the high morbidity and relapse rates associated with surgical interventions make less invasive interventions highly desirable.

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infections, which remains a cause of morbidity and death. Suppression commonly occurs in the first days after cessation of glucocorticoid therapy, but the exact duration is unclear. This review is an update of a previously published Cochrane review.

Vandetanib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during vandetanib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models, depending on the heterogeneity of trials. Twenty-two trials with 6382 patients were included summary incidences of all-grade gastrointestinal events in patients with cancer were anorexia 24% (95% CI, 20%-28%), constipation 17% (95% CI, 13%-20%), diarrhea 46% (95% CI, 40%-53%), nausea 29% (95% CI, 25%-33%), and vomiting 17% (95% CI, 14%-21%). Incidences of vandetanib-associated gastrointestinal events stratified by tumor histology were statistically insignificant. Vandetanib was associated with a significant risk of all-grade diarrhea (RR 1.75, 95% CI, 1.42-2.16) and high-grade diarrhea (RR 1.94, 95% CI, 1.43-2.64) and significantly decreased risk of all-grade constipation (RR 0.80, 95% CI, 0.71-0.91). Summary RR showed a significant risk of vandetanib-associated constipation (RR 0.82, 95% CI, 0.72-0.93) and diarrhea (all-grade: RR 1.68, 95% CI, 1.31-2.14 and high-grade: RR 1.57, 95% CI, 1.14-2.17) in patients with non-small-cell lung cancer. This study revealed a significantly increased risk of diarrhea and a reduced risk of constipation in patients with cancer receiving vandetanib, suggesting that appropriate and frequent clinical monitoring should be emphasized.

Management of cytotoxic drug extravasation remains contentious, with differing views on the most effective management strategy. With the increasing drive to provide effective, evidence-based healthcare, while ensuring the patient experience of the treatment provided plays a significant part in the development of clinical practice guidelines, the purpose of this literature review was to both critically analyse the quality of evidence that underpins contemporary practice and to determine if the patient experience is taken into account. A literature search was undertaken sourcing publications from the 1960s to July 2014 identifying all studies detailing strategies aimed at preventing the need for surgical debridement and all studies evaluating extravasation management from the patient's perspective. No conclusive evidence was found to suggest one clinical strategy as more effective than the other. No studies were identified that evaluated outcome from the patient's perspective. It is therefore suggested that outcomes-based research should underpin contemporary extravasation management guidelines to determine what the final outcome or 'end result' is and how this impacts on the patient and that the current lack of research into the patient experience of extravasation management is an area that needs to be addressed.

To estimate whether gonadotropin-releasing hormone (GnRH) analog administration during chemotherapy can protect against development of ovarian toxicity.

Virtual reality (VR), a computer-generated virtual environment, has been increasingly used in the entertainment world becoming a very new evolving field, but VR technology has also found a variety of applications in the biomedical field. VR can offer to subjects a safe environment within which to carry on different interventions ranging from the rehabilitation of discharged patients directly at home, to the support of hospitalized patients during different procedures and also of oncological inpatient subjects. VR appears as a promising tool for support and monitoring treatments in cancer patients influencing psychological and physiological functions. The aim of this systematic review is to provide an overview of all the studies that used VR intervention on cancer patients and analyze their main findings. Nineteen studies across nearly a thousand articles were identified that explored effects of VR interventions on cancer patients. Although these studies varied greatly in setting and design, this review identified some overarching themes. Results found that VR improved patients' emotional well-being, and diminished cancer-related psychological symptoms. The studies explored various relevant variables including different types of settings (i.e., during chemotherapy, during pain procedures, during hospitalization). Here, we point to the need of a global and multi-disciplinary approach aimed at analyzing the effects of VR taking advantage of the new technology systems like biosensors as well as electroencephalogram monitoring pre, during, and after intervention. Devoting more attention to bio-physiological variables, standardized procedures, extending duration to longitudinal studies and adjusting for motion sickness related to VR treatment need to become standard of this research field.

The anti-Epidermal Growth Factor Receptor monoclonal antibodies (anti-EGFR MoAbs) are beneficial in the treatment of wild type (WT) KRAS colorectal cancer, but are burdened by serious toxicities. We conducted a systematic review and meta-analysis to determine incidence and relative risk (RR) of severe and life-threatening diarrhoea and mucositis in colorectal cancer patients and WT-KRAS subpopulation. PubMed and Embase were searched for trials comparing the same therapeutic regimens with or without anti-EGFR for colorectal cancer. Data on severe and life-threatening diarrhoea and mucositis were extracted from 18 studies involving 13,382 patients. Statistical analyses calculated incidence of AEs, RRs and 95% confidence intervals by using either random or fixed effects models. Patients receiving anti-EGFR MoAbs showed an increased risk of diarrhoea (RR: 1.66, CI 1.52-1.80) and mucositis (RR: 3.44, CI 2.66-4.44). The risk was similar among WT-KRAS patients. Prevention and risk reduction strategies of these AEs are mandatory to optimize clinical outcomes.

Statins are commonly used against arteriosclerotic disease, but recent retrospective analyses have suggested that statins also prevent cancer. The aim of this systematic review is to verify the vitro anti-tumor effects of statins on head and neck squamous cell carcinoma.

Laser photocoagulation is the current gold standard treatment for proliferative retinopathy of prematurity (ROP). However, it permanently reduces the visual field and might induce myopia. Vascular endothelial growth factor (VEGF) inhibitors for the treatment of ROP may enable continuing vascularization of the retina, potentially allowing the preservation of the visual field. However, for their use in infants concern remains. This meta-analysis explores the safety of VEGF inhibitors.