Transportation of anticancer drugs such as anthracyclines across the membrane is regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 (ABCB1). Polymorphisms in the ABCB1 gene (1236C>T, 2677G>T/A, 3435C>T) have been found to be associated with intrinsic and acquired cross resistance to these anticancer drugs. Therefore, the aim of this study is to evaluate the influence of ABCB1 gene polymorphisms in breast cancer treatment outcomes in terms of response and toxicity.

Cardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy.

The association between glutathione-S-transferase P1 (GSTP1) Ile105Val polymorphism and oxaliplatin-induced neuropathy has been investigated in a number of published studies. However, most of these studies were based on small sample sizes and the results remained inconsistent. To assess the relationship between GSTP1 gene Ile105Val polymorphism and its susceptibility to oxaliplatin-induced neuropathy, a meta-analysis of previous studies was conducted.

Huachansu, a Chinese medicine that comes from dried toad venom from the skin glands of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has been used in treatment of cancers. We conducted a meta-analysis to evaluate the efficacy and safety of Huachansu combined with chemotherapy for advanced gastric cancer.

mTOR inhibitors are now approved by regulatory agencies for the treatment of a variety of malignancies. The risk of metabolic complications with these agents is not well characterized.

The use of rasburicase has been evaluated extensively in children, but not in adults. We review the current literature to evaluate its effect on adults.

Inhibition of the mammalian target of rapamycin (mTOR) is an established treatment for multiple malignancies. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with mTOR inhibitors.

Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC). This meta-analysis aimed to elucidate the effect of Ts polymorphisms on the efficacy of 5-FU-based chemotherapy in GC and CRC patients. Individual data were analyzed from 10 studies of 1102 GC and CRC patients treated with 5-FU-based regimens. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Data were pooled using the program STATA version 10.0 (Stata Corporation, College Station, TX). The relationship between the Ts polymorphism and survival following 5FU-based treatment of GC and CRC patients was systematically summarized. Compared with the C allele, the G allele was associated with shorter PFS but with similar OS in Caucasian CRC patients. Compared with the 3R/3R genotype, the 2R/3R or 2R/2R genotype was associated with the same PFS, but with a shorter OS, particularly in Caucasian CRC patients. These results show a correlation between survival following 5-FU-based therapy and tumor genotype in Caucasian CRC patients. Larger studies and further clinical trials are required to confirm this observation.

The purpose of this study was to estimate the risk and severity of oral and gastrointestinal mucosal toxicities associated with selected targeted agents.

Sorafenib, a multi-kinase inhibitor, has been reported to be associated with hypertension (HTN). However, the risk of severe HTN with sorafenib treatment has not been well described. We performed an up-to-date meta-analysis of high-grade HTN in cancer patients treated with sorafenib. Medline databases and the American Society of Clinical Oncology online database of meeting abstracts were searched up to August 2012 for relevant clinical trials. Eligible studies included phase II and III trials of sorafenib in patients with any type of cancer describing events of HTN according to the Common Terminology Criteria for Adverse Events. The summary incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated. The incidence of sorafenib-associated high-grade (grade 3-4) HTN was 6.0% (95% CI 4.7-7.3) in a total of 4722 patients from 55 trials of sorafenib as a single agent. Sorafenib-treated patients (4878 subjects from 13 randomized trials) had a significantly higher risk of high-grade HTN (RR 3.20 (95% CI 2.19-4.68)). Subgroup analysis revealed a significantly higher RR of high-grade HTN in patients receiving sorafenib as a single agent compared with patients receiving concomitant chemotherapy or immunotherapy (P=0.0076). The incidence of high-grade HTN associated with sorafenib was significantly higher in patients with renal cell carcinoma (RCC) than those with non-RCC cancer (P<0.0001) as well as patients treated with sorafenib for a longer duration than those treated for a shorter duration (P=0.003). The use of sorafenib is associated with a significantly higher risk of high-grade HTN compared with control.

Uncertainty exists regarding benefits of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation (CAD) for treatment of prostate cancer. On the basis of a systematic review of evidence, our aim was to formulate a recommendation for either IAD or CAD to treat relapsing, locally advanced, or metastatic prostate cancer.

There has been no universally agreed standard chemotherapy regimen for patients with advanced biliary tract carcinomas (BTC). We aimed to fully display and evaluate the clinical evidence for gemcitabine or gemcitabine-cisplatin combination for advanced BTC.

By carrying out a meta-analysis of randomized controlled trials that compared sorafenib or combined chemotherapy with placebo or combined chemotherapy, the effectiveness of sorafenib in hepatocellular carcinoma was evaluated in the present study, which also provided clinical practice guidelines of evidence-based-medicine.

To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).

Several observational studies have shown that statins may modify the risk of gastric cancer (GC). We carried out a systematic review and meta-analysis of studies evaluating the effect of statins on GC risk.

A growing body of evidence suggests that bisphosphonates may have chemopreventive potential against colorectal cancer. Our aim was to examine this association through a meta-analysis of observational studies.

The angiogenesis inhibitor pazopanib has been approved for the treatment of advanced renal cell cancer (RCC) and soft tissue sarcoma. Severe and fatal hepatotoxicity has been observed in its clinical studies. This analysis was conducted to determine the risk of liver toxicity by a systematic review and meta-analysis of clinical trials.

Despite the long-standing and extensive use of mitoxantrone (MTZ) for the treatment of aggressive forms of multiple sclerosis (MS), especially in Europe, its benefit-risk profile remains controversial. In particular, the risk of developing therapy-related acute leukemia (TRAL) and cardiotoxicity have led to treatment restrictions for MTZ; however, the precise risk for these severe complications is still unclear. Here we review current data on TRAL incidence, research strategies aimed at individual risk stratification, and provide recommendations for hematologic monitoring. A recent meta-analysis indicates a TRAL risk of approximately 0.81%, more than 10-fold higher than in previously reported meta-analyses (0.07%). There also appear to be considerable differences among countries, with recent TRAL risk estimates from Italy as high as 0.93%, compared to the 0.25%-0.41% risk reported from Germany and France. Whereas methodologic differences may partly account for some of these differences, high regional variability may point to exogenous factors such as heterogeneous treatment protocols and cotreatments. In addition, genetic risk factors (MTZ metabolism, DNA repair) might contribute to the individual risk profile. The case of potentially curable MTZ-induced secondary leukemia highlights the need for close hematologic monitoring during and after therapy. Intensive collaboration between neurologists and hematologists will likely provide benefits both for research efforts aimed at unraveling TRAL pathogenesis and for clinical practice with improved identification and monitoring of patients at higher risk of MTZ-induced TRAL. This is of particular importance, since treatment alternatives, especially in secondary progressive MS, are sparse.

The aim of this meta-analysis was to summarize the efficacy and safety of bevacizumab in the treatment of ovarian cancer.

A whole-genome approach was used to investigate the genetic determinants of cytarabine-induced cytotoxicity. We performed a meta-analysis of genome-wide association studies involving 523 lymphoblastoid cell lines (LCLs) from individuals of European, African, Asian, and African American ancestry. Several of the highest-ranked single-nucleotide polymorphisms (SNPs) were within the mutated in colorectal cancers (MCC) gene. MCC expression was induced by cytarabine treatment from 1.7- to 26.6-fold in LCLs. A total of 33 SNPs ranked at the top of the meta-analysis (P < 10(-5)) were successfully tested in a clinical trial of patients randomized to receive low-dose or high-dose cytarabine plus daunorubicin and etoposide; of these, 18 showed association (P < .05) with either cytarabine 50% inhibitory concentration in leukemia cells or clinical response parameters (minimal residual disease, overall survival (OS), and treatment-related mortality). This count (n = 18) was significantly greater than expected by chance (P = .016). For rs1203633, LCLs with AA genotype were more sensitive to cytarabine-induced cytotoxicity (P = 1.31 × 10(-6)) and AA (vs GA or GG) genotype was associated with poorer OS (P = .015), likely as a result of greater treatment-related mortality (P = .0037) in patients with acute myeloid leukemia (AML). This multicenter AML02 study trial was registered at www.clinicaltrials.gov as #NCT00136084.