Although endometrial adenocarcinoma is a common gynaecological cancer, a comparatively small proportion of patients present with, or develop, recurrent or advanced disease. However, for those women whose disease does progress or recur the prognosis is poor and the best treatment is yet to be identified. Co-morbidity, including obesity and cardiac disease, and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.

Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GISTs). To evaluate the efficacy and safety of two dose of imatinib treatment for patients with GISTs, a meta-analysis was performed.

Pemetrexed plus platinum has shown efficacy as a first-line treatment for advanced non-small cell lung cancer (NSCLC), but little is known about its efficacy and safety in East Asian patients. We report the final analysis of overall survival (OS) from a multicentre, randomized, phase II trial in chemotherapy-naive Chinese patients with advanced NSCLC. An additional meta-analysis was performed to systematically evaluate pemetrexed/platinum as first-line treatment for advanced NSCLC.

To perform a systematic review and meta-analysis of published clinical trials to determine incidence rate and overall risk of hypertension with vandetanib in cancer patients.

Although neoadjuvant chemotherapy (NCT) is widely used, it is not clear which subgroup of locally advanced non-small-cell lung cancer (NSCLC) patients should be treated with this approach, and if a particular benefit associated with NCT exists. In this study, we aimed to investigate the potential correlates of benefit from NCT in patients with NSCLC.

Current guidelines are inconclusive regarding intravenous (IV) iron for treatment of chemotherapy-induced anaemia (CIA).

Data from two randomized trials, evaluating a single-day regimen of palonosetron plus dexamethasone against emesis due to moderately emetogenic chemotherapy, were assessed for the impact of age on outcome in a pooled sample of women receiving anthracycline and/or cyclophosphamide (AC)-containing chemotherapy.

Zoledronic acid is widely used as adjuvant chemotherapy for the treatment of breast cancer. However, previous trials reported inconsistent findings regarding their clinical efficacy and safety. We carried out a comprehensive systematic review and meta-analysis to evaluate the effects of zoledronic acid on disease-free survival (DFS), overall survival (OS), and drug-related toxicities.

To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC) versus systemic chemotherapy for stage III/IV pancreatic cancer.

Registration of new anticancer drugs is usually based on results of randomized controlled trials (RCTs) showing improved efficacy when compared with standard therapy. There is relatively less emphasis on toxicity. In our study, we analyze serious toxicities of newly approved anticancer drugs reported in pivotal RCTs used for drug registration.

The definitive effect of induction chemotherapy (IC) on locally advanced head and neck squamous cell carcinoma (HNSCC) remains uncertain and although randomized controlled trials are supposed to provide high levels evidence for clinical guidelines, the data thus far has been conflicted. In an effort to elucidate the potential benefit of IC, a meta-analysis of randomized controlled trials (1965-2011) was performed investigating the impact of IC on survival, locoregional control, distant metastasis, and toxicity in HNSCC. Kaplan-Meier curves were read by a digitizing software-Engauge Digitizer. Data combination was performed using the software-RevMan and trial level log hazard ratio (HR) and variance were pooled and presented. Among the 40 eligible trials, 28 trials encompassing 4189 patients receiving locoregional treatment with or without IC were included in the analysis. The cumulative benefit of IC on overall survival and distant metastasis was 6% (HR = 0.94, 95%CI = 0.87-1.01, P = 0.11) and 7% (95%CI = 0-13%, P = 0.05) respectively while for locoregional control a benefit was not observed as seen by the -2% (95%CI = -11% to 8%, P = 0.73) improved control rate. In a subsite analysis specifically for laryngeal preservation, IC did not significantly improve survival (P = 0.47). There was a significant benefit from the cisplatin and 5-fluorouracil (PF) protocols with an increase in overall survival of 13% (HR = 0.87, 95%CI = 0.78-0.97, P = 0.01), and a reduction in the 5-year distant metastasis rate of 11% (95%CI = 0-21%, P = 0.04). The occurrence of grade 3/4 mucositis, leukopenia and emesis was significantly lower in patients receiving IC compared to patients receiving concomitant chemoradiotherapy. In conclusion, there is not a significant benefit of the pooled IC regimens in HNSCC on survival or locoregional control. In contrast, IC does show significant benefit in the reduction of distant metastasis. When protocols using a PF regimen are analyzed independently, a significant improvement in survival and rate of distant metastases is observed while there is not a benefit in locoregional control. The routine use of IC is still debatable. IC could be applied on larynx preservation strategy.

Dermatological toxicity, usually in the form of acneiform rash, is frequently observed in non-small-cell lung cancer (NSCLC) patients treated with anti-EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs). The objective of this review was to assess the predictive value of skin rash for outcome in patients with NSCLC treated with erlotinib and gefitinib.

Toremifene (TOR) and tamoxifen (TAM) can both be used as treatments for advanced breast cancer.

This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.

Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. It was recently approved by the US FDA for use in combination with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Rash is inconsistently reported as a common adverse event in most clinical trials of pertuzumab, at varying incidences. In this study, we have investigated the overall incidence and risk of rash with pertuzumab. Relevant studies were identified from the PubMed database (1966-2012), abstracts presented at the American Society of Clinical Oncology annual conference (2004-2011), and Web of Science database (1998-2012). Eligible studies were prospective phase II-III clinical trials using pertuzumab in cancer patients. Incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Data from a total of 1,726 patients (pertuzumab, n = 1,157; controls, n = 569) with breast, ovarian, and prostate cancers from eight clinical trials were included for analysis. The incidence of all-grade and high-grade rash with pertuzumab were 24.6 % (95 % CI 19.3-30.8 %) and 1.1 % (95 % CI 0.5-2.2 %), respectively. The risk varied with tumor types, as patients with prostate cancer had a lower incidence of rash (13.2 %; 95 % CI 8.0-21.1 %) than those with breast, ovarian, fallopian tube, and peritoneal cancer (P = 0.001). Overall, pertuzumab significantly increased the risk of rash in comparison with controls (RR 1.53; 95 % CI 1.12-2.09; P = 0.007). Pertuzumab is associated with a significant risk of rash, and the incidence varies among different tumor types. Prevention, early recognition, and appropriate treatment of this rash may lead to improvement in patient quality of life, adherence to therapy, and possibly optimize clinical outcomes.

The aim of the study was to perform a meta-analysis of the efficacy and safety of (bortezomib plus lenalidomide/thalidomide)- vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. We searched electronic and printed sources for relevant articles published. Inclusion criteria was as follows: randomized controlled trials (RCT) of (bortezomib plus lenalidomide/thalidomide) vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. Two reviewers independently assessed potentially eligible studies and extracted relevant data. We retrieved five RCT studies including a total of 1,200 patients. Using the random-effects model to pool the five RCT with a statistically significant heterogeneity (P = 0.03; X² = 10.69; df = 4; I² = 63%), the weighted risk ratios of a complete response (CR) for (bortezomib plus lenalidomide/thalidomide)-containing regimens was 1.81 (P = 0.005; 95% CI: 1.20-2.73). When we excluded the study by Cavo et al. (Lancet 376:2075-2085, 2010), the pooled risk ratio for CR was 1.59 (P < 0.0001, 95% CI: 1.29-1.96) with no statistically significant heterogeneity (P = 0.54; X² = 2.14; df = 3; I² = 0%) among four RCT under the fixed effects mode. The pooled odds ratio for the main grade III/IV adverse events (the peripheral neuropathy, thrombotic events, and infections) were 1.76 (P = 0.32; 95% CI: 0.58-5.31), 0.92 (P = 0.76, 95% CI: 0.52-1.61), and 1.05 (P = 0.82, 95% CI: 0.70-1.57), respectively. Our analysis showed (bortezomib plus lenalidomide/thalidomide)-containing regimens as induction treatment in newly diagnosed multiple myeloma improved CR but did not increase the risk of major adverse events (the peripheral neuropathy, thrombotic events, and infections).

We conducted a systematic review and bibliometric network analysis (SeBriNA) of rituximab for non-Hodgkin's lymphoma.

Angiogenesis is an important host process that interacts with cancer cells to promote growth, invasion, and metastasis. Numerous therapeutic agents targeting the VEGF pathway have been developed. Host variability in VEGF pathway can influence angiogenesis-dependent signaling, altering sensitivity to antiangiogenic drugs and prognosis. A systematic review and meta-analysis was conducted (May 1990-July 2011). Eligible studies involved cancer patients and compared polymorphisms in the VEGF pathway [VEGF and molecules directly interacting with VEGF: KDR, FLT1, FGF, FGF2, FGFR, NRP1, endostatin (encoded by COL18A1)], and reported one of the following outcomes: overall survival, progression-free survival, time to recurrence, disease-free survival, response rate, or drug toxicity. We identified 48 cancer studies assessing prognosis and 12 cancer studies exploring pharmacogenetics of anti-VEGF therapy across various VEGF pathway polymorphisms. There was marked inter- and intradisease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analyses of 5 VEGF polymorphisms (+936C>T, -460T>C, +405G>C, -1154G>A, and -2578C>A) identified a significant prognostic relationship: VEGF +405G>C variants showed a highly statistically significant improvement in overall survival [HR, 0.74; 95% confidence interval, 0.60-0.91; P = 0.004]. Variants (heterozygotes and/or homozygotes) of VEGF +405G>C were significantly associated with improved survival in a meta-analysis of multiple cancer sites.

Most patients with advanced non-small-cell lung cancer (NSCLC) require systemic chemotherapy. Chemotherapy plus multitargeted antiangiogenic tyrosine kinase inhibitors (TKI; e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, axitinib) has recently been evaluated in patients with NSCLC. However, the advantage of this therapy over chemotherapy alone in patients with advanced NSCLC remains largely unknown.

Aromatase inhibitors (AI) are currently the first line therapy for estrogen receptor (ER)-positive postmenopausal women. De novo AI resistance is when a patient intrinsically does not respond to an AI therapy as well as other targeted endocrine therapy. To characterize this type of resistance and to examine potential therapies for treatment, we have generated two cell models for de novo resistance. These models derive from MCF-7 cells that stably overexpress aromatase and Akt (AKT-aro) or HER2 (HER2-aro). Evaluation of these cell lines revealed that the activities of aromatase and ER were inhibited by AI and ICI 187280 (ICI) treatment, respectively; however, cell growth was resistant to therapy. Proliferation in the presence of the pure anti-estrogen ICI, indicates that these cells do not require ER for cell growth and distinguishes these cells from the acquired AI resistant cells. We further determined that the HSP90 inhibitor 17-DMAG suppressed the growth of the AI-resistant cell lines studied. Our analysis revealed 17-DMAG-mediated decreased expression of growth promoting signaling proteins. It was found that de novo AI resistant AKT-aro and HER2-aro cells could not be resensitized to letrozole or ICI by treatment with 17-DMAG. In summary, we have generated two cell lines which display the characteristics of de novo AI resistance. Together, these data indicate the possibility that HSP90 inhibitors may be a viable therapy for endocrine therapy resistance although additional clinical evaluation is needed.