We performed a systematic review and meta-analysis of hematologic toxicities associated with everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor. Eligible studies included phase II and III trials of patients with solid tumors on 10mg of everolimus daily describing events of neutropenia, thrombocytopenia, anemia or lymphopenia. The incidence of everolimus-associated all-grade and high-grade (Grade 3-4) hematologic toxicities were, respectively: neutropenia: 21.7% and 3.6%; thrombocytopenia: 36.0% and 4.7%; anemia: 61.2% and 8.4% and lymphopenia: 40.9% and 14.9%. Everolimus was associated with an increased risk of all-grade neutropenia (RR=2.24, [95% CI 1.51-3.32]), all-grade (RR=9.19, [95% CI 4.51-18.70]) and high-grade (RR=7.46, [95% CI 2.58-21.61]) thrombocytopenia, all-grade (RR=1.58, [95% CI 1.25-1.99]) and high-grade (RR=3.92, [95% CI 1.46-10.52]) anemia and all-grade (RR=1.72, [95% CI 1.50-1.97]) and high-grade (RR=2.70, [95% CI 1.86-3.93]) lymphopenia.

Non-muscle-invasive bladder cancer (NMIBC) commonly recurs, requiring invasive and costly transurethral resection of bladder tumor (TURBT). A meta-analysis of seven trials published in 2004 demonstrated that intravesical chemotherapy (IVC) following TURBT reduces recurrences. Despite European Association of Urology endorsement, adoption of this practice has been modest.

Concerns have arisen regarding the risk of ischemic heart disease with the novel antiangiogenic agent bevacizumab, a recombinant humanised monoclonal antibody to the vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in ischemic heart disease is controversial. This meta-analysis was therefore performed to assess the overall risk of ischemic heart disease associated with the use of bevacizumab. The databases of PubMed, EMBASE and Web of Science were searched for English language studies of randomised controlled trials comparing bevacizumab with control therapy published through October 25, 2012. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. A total of 4,617 patients from 7 randomised controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidence of ischemic heart disease was 1.0% (95% CI, 0.6%-1.4%). Patients treated with bevacizumab had a significantly increased risk of ischemic heart disease with an RR of 2.49 (95% CI, 1.37-4.52) compared with controls. In addition, both high doses and low doses of bevacizumab increased the risk of cardiac ischemia (low dose at 2.5 mg/kg per week: RR, 2.14 [95% CI, 1.09-4.19]; high dose at 5 mg/kg per week: RR, 4.81 [95% CI, 1.03-22.42]). Bevacizumab was also found to significantly increase the risk of cardiac ischemia in patients with colorectal cancer (RR, 2.13; 95% CI, 1.11-4.06) compared with controls. This meta-analysis shows the use of bevacizumab was associated with an increased risk of developing ischemic heart disease in colorectal cancer patients receiving this drug. Our conclusions are limited by the available data. Further evaluations of high-quality RCTs are needed.

Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes (OR 0.66; 95% confidence interval [CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett's esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined (OR 0.61; 95%CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have become the cornerstone in the treatment of lung cancers that harbor EGFR mutations, but also play an important role in the treatment of other lung cancers and have been investigated among various types of solid tumors. However, these drugs have been associated with an increase in the risk of potentially life-threatening adverse event, such as arterial and venous thrombotic events. We performed a meta-analysis to determine the incidence and risk of fatal adverse events (FAEs) in cancer patients treated with EGFR-TKIs. Incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using a random effects model. A total of 13,825 patients from 22 trials were included. Among patients treated with EGFR-TKIs, the overall incidence of FAEs was 1.9% (95%CI: 1.2-2.9%), and the risk of FAEs was 0.99 (95%CI: 0.70-1.41, p = 0.97). No increase in FAEs was detected in any prespecified subgroup. Additionally, using EGFR-TKIs as salvage treatment significantly reduced the risk of FAEs when compared to the controls (RR 0.51, 95%CI: 0.29-0.87, p = 0.013). In conclusion, this analysis suggests that the use of EGFR-TKIs does not increase the risk of FAEs in patients with advanced solid tumors, and EGFR-TKIs are safety and tolerable for cancer patients, especially for those previously treated patients.

Data from 30 pharmacogenomic studies that investigated MDR1 mRNA expression or gene variants (C3435T, G2677TA, C1236T) and response to therapy in acute myeloid leukaemia (AML) were synthesized. Anthracycline-based regimens were mainly used. MDR1 mRNA overexpression was associated with poor response to therapy [odds ratio (OR) = 2.49 95% confidence interval (CI) 1.38-4.50]. The gene variants were not associated with response to treatment; the generalized ORs, a genetic model-free approach, for the variants C3435T, G2677TA and C1236T were ORG = 0.86 (95% CI 0.55-1.37), ORG = 0.97 (95% CI 0.58-1.64) and ORG = 1.17 (95% CI 0.75--1.83), respectively. There is indication that MDR1 mRNA expression may be considered as a potential marker for response to chemotherapy in AML patients.

The objective of this study was to carry out a meta-analysis of the efficacy of gemcitabine+platinum agent regimens in the treatment of advanced biliary tract cancer (BTC). PubMed and Google Scholar were searched using the following combination of search terms: gemcitabine, oxaliplatin, cholangiocarcinoma, biliary, gallbladder, bile duct. Studies were eligible for inclusion in the meta-analysis if they were randomized trials on the use of gemcitabine plus a platinum agent for the treatment of advanced (unresectable or metastatic cancer) BTC. Outcomes of interest were response rate, overall survival, and progression-free survival. Pooled odds ratios/differences in median survival and 95% confidence intervals (CIs) were determined for each outcome. A total of 47 records were identified in the initial search. Ultimately, three open-label randomized trials (two phase 2 and one phase 3) met the eligibility criteria and were included in the meta-analysis. Two studies compared gemcitabine plus cisplatin with gemcitabine alone, whereas the other study compared gemcitabine plus oxaliplatin with fluorouracil-folinic acid. The total number of patients in the studies ranged from 54 to 410. The overall analyses revealed that all survival outcomes assessed were significantly more favorable for patients treated with gemcitabine plus platinum agents than for patients not treated with this combination. Response rates: odds ratio=2.639, 95% CI=1.210-5.757, Z=2.439, P=0.015; pooled difference in median overall survival=3.822 months, 95% CI=1.798-5.845 months, Z=3.702, P<0.001; pooled difference in median progression-free survival=3.268 months, 95% CI=1.996-4.541 months, Z=5.035, P<0.001. Patients with advanced BTC who are treated with gemcitabine plus platinum agents may experience better survival outcomes compared with patients who are not treated with this combination of chemotherapy.

Two novel mammalian targets of rapamycin (mTOR) inhibitors everolimus and temsirolimus are now approved by regulatory agencies and have been widely investigated among various types of solid tumors, but the risk of fatal adverse events (FAEs) with these drugs is not well defined.

Hodgkin lymphoma (HL) is one of the most common malignancies in young adults and has become curable for the majority of patients, even in advanced stage. After first-line therapy, 15% to 20% do not respond to treatment and relapse. For those patients, high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is a frequently used therapy option.

Cetuximab has been approved by FDA for the treatment of advanced/metastatic colorectal cancer. Whether cetuximab treatment is associated with an increase of severe adverse events in colorectal cancer (CRC) patients remains a question. The purpose is to assess the risk of severe adverse events of cetuximab treatment in advanced/metastatic CRC patients.

The high recurrence rate of hepatocellular carcinoma (HCC) after potentially curative treatment determines the long-term prognosis.

Lenalidomide is indicated for treatment of multiple myeloma in combination with dexamethasone and as a single agent in myelodysplastic syndromes. The incidence and risk of rash has been inconsistently reported.

Few studies have investigated the late (i.e. ≥ 5 years post-treatment) effects of chemotherapy for non-central nervous system (non-CNS) cancer on the brain. Here we discuss the studies that have investigated the late effects of adjuvant chemotherapy for non-CNS cancer on cognitive function (n=6); brain structure and function (n=5); and incidence of dementia (n=4). The neuropsychological studies showed long-term adverse cognitive problems in chemotherapy-exposed breast cancer survivors. This is in line with results from neuroimaging studies that report long-term brain structural alterations after chemotherapy. The studies exploring the association between chemotherapy and the incidence of dementia were contradictive and showed no clear relationship between the two phenomena. Although several methodological issues limit the validity and interpretation of some of the results of these studies, they suggest that chemotherapy is associated with subtle, yet long-lasting cognitive deficits, possibly related to brain structural and functional differences, but as yet not with an increased risk of dementia.

The addition of bevacizumab (BEV) to cytotoxic chemotherapy regimens (CTX) was believed to be effective; however, its magnitude of benefits is still controversial. So a meta-analysis and systematic review seems to be necessary.

Fulvestrant is an endocrine agent which degrades the estrogen receptor, thereby downregulating its signaling. Trials of fulvestrant are limited by inconsistent study populations and drug dosing. The optimal use of fulvestrant in advanced breast cancer is therefore unclear.

To assess the effect and safety of using single intravitreal bevacizumab (IVB) versus intravitreal triamcinolone acetonide (IVTA) and grid laser photocoagulation (GLP), or a combination of IVB and IVTA for treatment of retinal vein occlusion (RVO)-associated macular edema, mainly exploring its effects on visual acuity (VA) and central macular thickness (CMT).

This retrospective analysis was conducted to characterize ipilimumab exposure-response relationships for measures of efficacy and safety in patients with advanced melanoma.

Epithelial ovarian cancer (EOC) is a life-threatening disease. Most often women become symptomatic only in the advanced stages of the disease, increasing the difficulty of treatment. Whilst the disease responds well to surgery and chemotherapy, the relapse rate is high. New treatments to prevent disease recurrence or progression, prolong survival, and increase the quality of life are needed.

Mammalian target of rapamycin (mTOR) inhibitors are used in a variety of malignancies. Infections have been reported with these drugs. We performed an up-to-date meta-analysis to further characterise the risk of infections in cancer patients treated with these agents.

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancer but associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidence and relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, we searched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at the American Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 to December 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapy or biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients were included in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrile neutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95% CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31; 95% CI: 1.08-1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those who did not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly with tumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent, as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumab addition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may be dose-dependent.