Approximately one-fifth of women who develop early breast cancer have HER2-positive tumours, which if untreated, have a worse prognosis than HER2-negative tumours. Trastuzumab is a selective treatment targeting the HER2 pathway. Although the results on efficacy seem to support its use, there are potential cardiac toxicities which need to be considered, especially for women at lower risk of recurrence, or those at increased cardiovascular risk.

Carcinomas of unknown primary (CUP) approximately represent 2-3% of all adult cancers. Various clinicopathological subsets of CUP have been identified, which may be treated with tailored approaches. Nevertheless, 80% of CUP do not fall into these subsets. Even when at least 4 prognostic models have been developed and validated in independent patient cohorts, there is no consensus or reliable guidance for estimating the prognosis of these "unfavourable" CUP. Consequently, targeting patients who benefit from palliative chemotherapy is difficult. Thirty-eight phase II trials were published between 1997 and 2011; a systematic analysis of these trials did not allow the recommendation of any of the tested regimens as a standard of care. Currently, there is only one published phase III clinical trial (Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan); without significant difference between both regimens. Thus, with the promise of molecular profiling, we are waiting for a large collaborative clinical trial that validates the concept of targeted treatment in this population of patients with "unfavourable" CUP.

The wide variability in pharmacokinetics of busulfan in children is one factor influencing outcomes such as toxicity and event-free survival. A meta-analysis was conducted to describe the pharmacokinetics of busulfan in patients from 0.1 to 26 years of age, elucidate patient characteristics that explain the variability in exposure between patients and optimize dosing accordingly.

Daily aspirin reduces the long-term incidence of some adenocarcinomas, but effects on mortality due to some cancers appear after only a few years, suggesting that it might also reduce growth or metastasis. We established the frequency of distant metastasis in patients who developed cancer during trials of daily aspirin versus control.

Vandetanib is a small molecule inhibitor against vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR). The aim of this study is to evaluate the efficacy and safety of vandetanib as a second-line treatment for advanced non-small cell lung cancer (NSCLC).

Ototoxicity is a frequent adverse event of cisplatin treatment. No therapy is currently available for cisplatin-induced ototoxicity. A systematic review of experimental animal studies and in vitro experiments was conducted to evaluate gene therapy as a potential future therapeutic option.

Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection tyrosine kinases. It is approved for the treatment of unresectable or metastatic medullary thyroid cancer. Its use may be hindered due to adverse events, including rash. The reported incidence and risk of rash to vandetanib varies widely and has not been more closely investigated. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing a rash.

Cetuximab (C) and panitumumab (P) increase response rate and survival in KRAS wild-type metastatic colorectal cancer (mCRC). We performed a meta-analysis of randomised controlled trials (RCTs) to assess their effect on overall response rate (ORR), the rate of radical resection (R0) and survival in patients with liver-limited initially unresectable mCRC.

Venous thromboembolism (VTE) often complicates the clinical course of cancer disease. The risk is further increased by chemotherapy but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain.

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have become the cornerstone in the treatment of several malignancies. These drugs have also been associated with an increase in the risk of potentially life-threatening adverse events, such as arterial thrombotic events, bleeding, congestive heart failure, and others. We performed an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in patients with cancer treated with VEGFR TKIs.

It has been proposed that the level of class III β-tubulin gene expression can be used to predict clinical sensitivity to paclitaxel/vinorebine-based chemotherapy in non-small cell lung cancer (NSCLC) patients. However, whereas there are published reports supporting this association, there are also reports of studies that failed to find such an association. We conducted a meta-analysis of all relevant published data to provide a combined statistical assessment of the proposed association of expression variations of class III β-tubulin with objective response and median survival in patients with NSCLC treated with paclitaxel/vinorebine-based chemotherapy.

In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate ESA benefits and risks in lung cancer, we conducted meta-analyses of data from controlled ESA trials conducted in lung cancer patients. Study-level analyses included controlled ESA trials reporting lung cancer mortality, identified from the 2006 Cochrane ESA report and from a systematic search for studies published through December 2010. Patient-level analyses included data from lung cancer patients receiving chemotherapy in Amgen studies evaluating darbepoetin alfa (DA) vs placebo. Study-level and patient-level analyses examined deaths, progression, and transfusion incidence. Patient-level analyses also examined adverse events (AEs) and fatigue. In a study-level meta-analysis of nine ESA studies of 2342 patients receiving chemotherapy, the ESA odds ratio (OR) was 0.87 (95% confidence interval [CI] 0.69-1.09) for mortality; the overall random-effects risk difference (95% CI) for mortality was -0.02 (-0.06, 0.02). The ESA OR (95% CI) for disease progression in five chemotherapy studies reporting progression was 0.84 (0.65-1.09). The ESA odds ratio (95% CI) was 0.34 (0.28-0.41) for transfusion incidence. In a patient-level meta-analysis of four studies evaluating 1009 patients through follow-up, the median survival time was 41 weeks with DA and 38 weeks with placebo. During the combined study and follow-up periods, 80% of placebo-group patients and 74% of DA patients died (mortality hazard ratio [HR] 0.90 [95% CI, 0.78-1.03] for DA); results were similar for small cell lung cancer and non-small cell lung cancer. Overall, 87% of placebo patients and 84% of DA patients progressed or died. Fewer DA patients had transfusions (week 5 through end-of-study, DA 19%, placebo 43%). AEs included thrombotic/embolic events (DA 10.5%, placebo 7.2%), cerebrovascular disorders (DA 3.7%, placebo 4.2%), pulmonary edema (DA 0.4%, placebo 1.0%) and pulmonary embolism (DA 1.8%, placebo 0.6%). These meta-analyses suggest that ESAs reduce transfusions without increasing mortality or disease progression in lung cancer patients undergoing chemotherapy.

Recently, melatonin has been associated with cancer both in vitro and in vivo. However, the value of melatonin in the treatment of cancer remains disputable. Hence, we performed a systematic review of randomized controlled trials (RCTs) of melatonin in solid tumor cancer patients and observed its effect on tumor remission, 1-year survival, and side effects due to radiochemotherapy.

The benefit of taxanes in the adjuvant setting for node-negative (N0) early breast cancer (EBC) has not yet been established. We conducted a meta-analysis of randomized adjuvant trials comparing docetaxel-containing versus non-taxane-containing regimens. The purpose of this study was to determine whether the incorporation of docetaxel improves disease-free survival (DFS) and overall survival (OS) in early stage breast cancer. Studies were retrieved by searching major databases and the proceedings of leading breast cancer conferences. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for DFS and OS and obtained pooled estimates using an inverse-variance model. Fourteen randomized phase III studies were included (25,067 patients). The pooled HR estimate was 0.84 (95% CI 0.78-0.89; P < 0.001) favoring docetaxel for DFS and 0.86 (0.78-0.94; P < 0.001) for OS. In N0 patients (4,274 patients), the pooled HR estimate for DFS was 0.86 (0.73-1.00; P = 0.05). The HR for OS was equal to 1 (0.75-1.34). The improvement in DFS with docetaxel-containing regimens was observed across all subgroups (age, under or over 50; number of involved nodes; hormone receptor or HER2 status (including triple negative status), or administration schedule (sequential or concomitant). The addition of docetaxel to a non-taxane-containing regimen improves DFS and OS in high risk EBC patients. The benefit in DFS was seen across all subgroups regardless of nodal status, age, hormone receptor or HER2 status (including triple negative status), or administration schedule.

Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well established treatment for preventing or delaying tumour recurrence following tumour resection. However, up to 70% of patients may fail and new intravesical agents with improved effectiveness are needed. Gemcitabine is a relatively new anticancer drug that has shown activity against bladder cancer.

Anti-epidermal growth factor receptor (EGFR) agents [monoclonal antibodies (MoAbs), tyrosine kinase inhibitors (TKIs)] are targeted therapies used in advanced cancers. Arterial and venous thromboembolic events (ATEs and VTEs excluding catheter-related events) were not investigated with these agents, and the risk of these events is still unknown.

Published data on the dose of imatinib to treat gastrointestinal stromal tumors seemed inconclusive. To derive a more precise estimation of dose of imatinib to treat gastrointestinal stromal tumors, a meta-analysis was performed.

We conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing skin rash and stomatitis among patients receiving temsirolimus.

Cholangiocarcinoma is a heterogeneous disease with a poor outcome that accounts for 5%-10% of primary liver cancers. We characterized its genomic and genetic features and associated these with patient responses to therapy.

Axitinib, an orally administered inhibitor of vascular endothelial growth factor 1, 2 and 3, is primarily metabolized by cytochrome P450 (CYP) 3A4/5 but is also a substrate for CYP1A2, CYP2C19, UDP-glucuronosyltransferase (UGT)1A1 and the drug transporters P-glycoprotein (encoded by the ABCB1 gene) and OATP1B1 (encoded by SLC01B1). The potential contribution of polymorphisms in genes encoding these enzymes and transporters to axitinib pharmacokinetic variability was assessed.