Dose-dense chemotherapy has become a mainstay regimen in the adjuvant setting for women with high-risk breast cancer. We performed a systematic review and meta-analysis of the existing data from randomized controlled trials regarding the efficacy and toxicity of the dose-dense chemotherapy approach in nonmetastatic breast cancer.

Cetuximab is often used in patients with colorectal cancer, head and neck cancer, and other cancers. Hypomagnesemia is a major adverse event that was often ignored in studies. The aim of this meta-analysis is to gain a better understanding of the overall incidence and risk of hypomagnesemia in patients who received cetuximab-based therapy.

The role of the widely-used angiogenesis inhibitor bevacizumab in the development of serious hemorrhage is not well defined in cancer patients. This study was conducted to determine the overall risk of hemorrhage with bevacizumab by a systematic review and meta-analysis of randomized controlled trials (RCT).

It is still controversial that GnRH agonist (GnRHa) protects ovarian function from chemotherapy-induced gonadotoxicity. Indeed, the results of many studies related to this issue are neither consistent nor convincing because of the weak study design and the inadequate sample size. We identified 11 prospective controlled studies (8 nonrandomized and 3 randomized) for the systemic review and meta-analysis. The meta-analysis showed that GnRHa cotreatment during chemotherapy can protect ovarian function. However, it is worthy to note that the result of this meta-analysis is influenced by nonrandomized studies. The protective effect of GnRHa will remain elusive until the currently ongoing large, prospective, randomized studies are completed. In addition, tamoxifen, a selective estrogen receptor modulator, may have the protective effect against loss of follicles and ovarian function, which was caused by chemotherapy.

We performed a meta-analysis on adverse events seen with bevacizumab to combine the existing evidence about its safety in patients with advanced cancer.

• To estimate the benefits and harms of 5-α-reductase inhibitors (5-α-RIs) in preventing prostate cancer.

We performed a systematic review and meta-analysis to determine the impact of neutropenia or leukopenia experienced during chemotherapy on survival.

Trastuzumab is used widely for the treatment of early and advanced breast cancer. However, concerns have arisen regarding its cardiac toxicity. We did a systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess the overall risk of cardiac dysfunction associated with trastuzumab treatment.

Nausea and vomiting are still a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting and associated clinical problems.

The nursing profession has been associated with several adverse pregnancy outcomes. However, the associations between occupational exposures and adverse pregnancy outcomes among this group have not been systematically examined. This review collates all epidemiological evidence to examine the strength of associations and consistency among eligible studies.

Whether gemcitabine plus platinum chemotherapy is superior to gemcitabine or platinum single-agent chemotherapy for patients with non-small cell lung cancer (NSCLC) is still in dispute, and the aim of this study is to evaluate the efficacy and safety of gemcitabine combining platinum chemotherapy for patients with NSCLC.

Ovarian cancer (OC) is associated with a >75% risk of recurrence after completion of primary therapy. Several clinical trials have explored the role of continued therapy after complete response to primary adjuvant therapy to reduce the risk of recurrence; however, these trials have largely been underpowered, leading to inconclusive results.

A previous meta-analysis showed that the association between the UGT1A1*28 genotype and irinotecan-induced neutropenia was influenced by irinotecan dose and that the risk of neutropenia was similar at low doses for patients with all genotypes. However, the sample sizes for the low- and high-dose groups were small. Because additional studies have now been reported, an updated and refined meta-analysis is needed.

Second (2nd)-generation tyrosine kinase inhibitors (TKI) (dasatinib, nilotinib) are effective in patients with all phases of chronic myeloid leukaemia (CML). Dose reductions and treatment interruptions are frequently required due to toxicity, but their significance is unknown. We analysed the impact of dose reductions/interruptions and dose intensity of 2nd-generation TKI on response and survival. A total of 280 patients with CML (all phases) were analysed. Dose reductions were considered when the daily dose was below the standard dose. Dose intensity was determined based on the percentage of the ideal dose intensity. Overall, 176 patients (63%) required treatment interruptions and/or dose reduction at least once during therapy. Dose reductions/interruptions, analysed as a time-dependent covariate, were associated with worse failure-free survival only in patients with untreated CML. Dose intensity analysis did not reveal a worse response or survival in patients who received a lower dose intensity (<100%) during therapy or during the first 6 months. In conclusion, dose reductions and treatment interruptions of 2nd generation TKI in patients with CML have a minimal impact in the response rate and survival of these patients. Further studies are required to determine whether there might be a minimum adequate dose of these agents.

Treatment with the chemotherapeutic agent bevacizumab, a humanized mAb that neutralizes vascular endothelial growth factor, can lead to proteinuria and renal damage. The risk factors and clinical outcomes of renal adverse events are not well understood. We performed a systematic review and meta-analysis of published randomized, controlled trials to assess the overall risk for severe proteinuria with bevacizumab. We analyzed data from 16 studies comprising 12,268 patients with a variety of tumors. The incidence of high-grade (grade 3 or 4) proteinuria with bevacizumab was 2.2% (95% confidence interval [CI] 1.2 to 4.3%). Compared with chemotherapy alone, bevacizumab combined with chemotherapy significantly increased the risk for high-grade proteinuria (relative risk 4.79; 95% CI 2.71 to 8.46) and nephrotic syndrome (relative risk 7.78; 95% CI 1.80 to 33.62); higher dosages of bevacizumab associated with increased risk for proteinuria. Regarding tumor type, renal cell carcinoma associated with the highest risk (cumulative incidence 10.2%). We did not detect a significant difference between platinum- and non-platinum-based concurrent chemotherapy with regard to risk for high-grade proteinuria (P = 0.39). In conclusion, the addition of bevacizumab to chemotherapy significantly increases the risk for high-grade proteinuria and nephrotic syndrome.

The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT₃ receptor antagonists to assess its translational validity.

The objective of this work is to perform a systematic review and meta-analysis of all randomized controlled trials comparing a single intravenous dose of palonosetron (PAL) 0.25 mg with other 5-HT(3)R in patients receiving moderately or highly emetogenic (MoHE) chemotherapy.

The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied.

To evaluate the efficacy and safety in treatment of ocular neovascularization by Bevacizumab versus Ranibizumab.

Preclinical cellular response profiling of tumor models has become a cornerstone in the development of novel cancer therapeutics. As efforts to predict clinical efficacy using cohorts of in vitro tumor models have been successful, expansive panels of tumor-derived cell lines can recapitulate an "all comers" efficacy trial, thereby identifying which tumors are most likely to benefit from treatment. The response profile of a therapy is most often studied in isolation; however, drug treatment effect patterns in tumor models across a diverse panel of compounds can help determine the value of unique molecular target classes in specific tumor cohorts. To this end, a panel of 19 compounds was evaluated against a diverse group of cancer cell lines (n = 311). The primary oncogenic targets were a key determinant of concentration-dependent proliferation response, as a total of five of six, four of four, and five of five phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, insulin-like growth factor-I receptor (IGF-IR), and mitotic inhibitors, respectively, clustered with others of that common target class. In addition, molecular target class was correlated with increased responsiveness in certain histologies. A cohort of PI3K/AKT/mTOR inhibitors was more efficacious in breast cancers compared with other tumor types, whereas IGF-IR inhibitors more selectively inhibited growth in colon cancer lines. Finally, specific phenotypes play an important role in cellular response profiles. For example, luminal breast cancer cells (nine of nine; 100%) segregated from basal cells (six of seven; 86%). The convergence of a common cellular response profile for different molecules targeting the same oncogenic pathway substantiates a rational clinical path for patient populations most likely to benefit from treatment. Cancer Res; 70(9); 3677-86. (c)2010 AACR.