Although the addition of bevacizumab significantly improves the efficacy of chemotherapy for advanced breast cancer, regulatory concerns still exist with regard to the magnitude of the benefits and the overall safety profile.

Bladder cancer accounts for approximately 4.4% of adult malignancies, and approximately 80% of bladder cancer presents initially as transitional cell carcinoma that is confined to the urothelium (stage Ta) or lamina propria (stage T1). Intravesical administration of Bacillus Calmette-Guérin (BCG) and epirubicin (EPI) has been proven to reduce tumour recurrence and prevent or delay progression to muscle invasion and metastases. However, comparison of the effectiveness and safety of intravesical BCG and EPI in bladder cancer has yet to be explored.

Paclitaxel has become a standard drug used in a number of common cancers. At first long infusions were used to reduce the rate of inflow of the drug and as a result reduce the occurrence of hypersensitivity types of allergic reactions. Trials with shorter durations of infusion, and using a cocktail of anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were begun. These were interpreted as showing that effectiveness of treatment was not lessened by a short infusion time. These studies also appeared to show that some important toxicities were less common with short infusions and that they were more convenient for the patient and the hospital.

Vascular endothelial growth factor (VEGF) may play a role in erythropoiesis. We performed a meta-analysis of randomized controlled trials (RCT) to determine the effect of the anti-VEGF antibody bevacizumab on anemia in cancer patients treated with chemotherapy.

Compared to tamoxifen, the efficacy and side effects of toremifene in adjuvant endocrine therapy for breast cancer were not very clear. This meta-analysis was conducted to give a more precise estimation of the efficacy and severe side effects of toremifene given in the adjuvant setting in comparison to tamoxifen. The electronic database PubMed was searched for randomized trials comparing toremifene with tamoxifen as adjuvant therapies. Four randomized trials published in three articles were eligible, including 1,890 pooled cases treated with toremifene and 1,857 cases treated with tamoxifen. Compared to patients in tamoxifen group, patients in toremifene group did not have a significantly different overall survival rate (risk ratio (RR): 1.07, 95% confidence interval (CI): 0.97-1.19, P = 0.994 for heterogeneity) or a disease-free survival (DFS) rate (RR: 1.05, 95% CI: 0.95-1.17, P = 0.431 for heterogeneity) at the end of the follow-up time. The rates of thromboembolic events in toremifene group, including deep vein thrombosis (odds ratio (OR): 0.68, 95% CI: 0.40-1.17, P = 0.926 for heterogeneity), cerebrovascular accident (OR: 0.59, 95% CI: 0.32-1.09, P = 0.438 for heterogeneity), and pulmonary embolism (OR: 0.91, 95% CI: 0.42-2.01, P = 0.618 for heterogeneity), were not significantly different from those in tamoxifen group. The rates of endometrial polyps and endometrial cancer between the two groups were almost the same. This meta-analysis suggested that toremifene was as effective as tamoxifen in the adjuvant setting for both perimenopausal and postmenopausal breast cancer patients with similar severe adverse effects to tamoxifen. Toremifene was a convincing and safe change for tamoxifen in adjuvant endocrine therapy.

The relationship between non-steroidal anti-inflammatory drug (NSAID) use and esophageal squamous cell carcinoma (ESCC) has remained unclear. To evaluate the relationship between NSAID use and risk of ESCC, we searched the MEDLINE, Biosis, Web of Science and ISI proceedings databases up to September 2010, together with a manual search of reference lists of relevant articles. Studies evaluating the association between exposure to NSAIDs and risk of ESCC were included. The analyses used random-effect or fixed-effect model based on homogeneity analysis. Seven studies (six case-control studies and one nested case-control study) were included in this meta-analysis. NSAID use was associated with a reduced risk of ESCC (odds ratio = 0.58, 95% confidence interval = 0.47 to 0.72). Specific analysis for aspirin and non-aspirin NSAIDs yielded similar results. There was a protective association between NSAIDs and ESCC. This finding warrants more prospective studies evaluating the relationship between NSAIDs and ESCC.

This study compared the efficacy and toxicities of cetuximab combined with chemotherapy versus chemotherapy for patients with metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on the outcomes was also investigated.

We present previously unknown evidence that the immunoglobulin heavy chain binding protein BIP/HSPA5, also known as glucose regulated protein (GRP)78, serving as a pivotal component of the pro-survival axis of the unfolded protein response (UPR) signalling network, is abundantly expressed in relapsed B-lineage acute lymphoblastic leukaemia (ALL) and contributes to chemotherapy resistance of leukaemic B-cell precursors. The resistance of B-lineage ALL cells to the standard anti-leukaemic drug vincristine was overcome by the HSPA5 inhibitor epigallocatechin gallate, which inhibits the anti-apoptotic function of HSPA5 by targeting its ATP-binding domain. Notably, chemotherapy-resistant B-lineage ALL cells underwent apoptosis within 48 h of exposure to a doxorubicin-conjugated cell-penetrating cyclic anti-HSPA5 peptide targeting surface-expressed HSPA5 molecules on leukaemia cells. The identification of the HSPA5 as a chemoresistance biomarker and molecular target for B-lineage ALL may lead to new anti-leukaemic treatment strategies that are much needed.

A meta-analysis was performed to determine the type, incidence and risks of dermatological toxicities associated with the multikinase inhibitor sorafenib. A literature search was performed using the electronic databases PubMed and EMBASE, and conference abstracts published by the American Society of Clinical Oncology. Eligible studies included prospective phase II or III clinical trials, and expanded-access programmes (i.e. outside a clinical trial) of patients with solid tumours assigned sorafenib at a starting dose of 400 mg twice daily. The overall incidences and risk ratios of dermatological toxicities associated with sorafenib were analysed. For patients assigned sorafenib, the overall incidence of all-grade rash/desquamation was 35.4% (95% CI 0.29-0.43), hand-foot skin reaction (HFSR) 39.0% (95% CI 0.32-0.47), alopecia 25.5% (95% CI 0.18-0.35), pruritus 14.0% (95% CI 0.10-0.20) and dry skin 14.1% (95% CI 0.10-0.20). High-grade rash/desquamation events occurred in 5.0% (95% CI 0.04-0.07), HFSR in 9.0% (95% CI 0.082-0.098), alopecia in 4/1793, pruritus in 2/1265 and dry skin in 0/1689 of patients assigned sorafenib. Meta-analysis of risk ratio showed that sorafenib was associated with a significantly increased risk of rash/desquamation [risk ratio (RR) 2.73; 95% CI 1.66-4.49)], HFSR (RR 7.50; 95% CI 3.90-14.40) and alopecia (RR 7.55; 95% CI 5.26-10.84) in patients with solid tumours, but risk of pruritus (RR 1.80; 95% CI 0.77-4.22) or dry skin (RR 2.18; 95% CI 0.88-5.40) was not increased. In conclusion, the most frequent dermatological toxicities associated with sorafenib were HFSR, rash/desquamation, alopecia, pruritus and dry skin. There was a significantly increased risk of HFSR, rash/desquamation and alopecia with sorafenib compared with placebo. Skin toxicities were mainly mild or moderate in severity. Appropriate prevention and management are recommended.

Malignant grade and death rate are very high for non-small cell lung cancer, and gefitinib is a new molecule target anticancer drug. The aim of this meta analysis is to evaluate the clinical efficacy and safety of gefitinib for non-small cell lung cancer.

The prognosis for unresectable, locally advanced or metastatic transitional cell carcinoma of the bladder is poor with most patients succumbing to their disease within 2 to 3 years. Clinical management at this stage of the disease is palliative with systemic chemotherapy the main treatment of choice. A number of cytotoxic agents have shown activity in metastatic disease including cisplatin, methotrexate, doxorubicin and vinblastine. However, response rates still need improving and toxicities may sometimes be severe, and so the search for newer agents with improved benefit-to-risk ratios is constantly being pursued. One such agent that shows promise is gemcitabine.

Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN.

Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers).

The addition of Rituximab (R) to standard chemotherapy (C) has been reported to improve the end of treatment outcome in patients affected by CD-20 positive malignant lymphomas (CD20+ ML). Nevertheless, given the profound and prolonged immunosuppression produced by R there are concerns that severe infections may arise. A systematic review and meta-analysis were performed to determine whether or not the addition of R to C may increase the risk of severe infections in adults undergoing induction therapy for CD20+ ML.

Nearly one third of non-small cell lung cancer (NSCLC) patients at diagnosis have stage III disease. Concurrent chemoradiation has emerged as the standard of care for patients with unresectable stage III NSCLC. Meta-analyses of studies comparing concurrent with sequential therapy showed that there was a relative improvement of about 20% with concurrent therapy over sequential therapy in these patients and that concurrent chemoradiation is more toxic than the sequential approach, particularly with regard to esophagitis. The incidence of pneumonitis is not significantly higher with concurrent therapy. All the phase 3 trials comparing concurrent with sequential therapy included cisplatin-based therapy. In addition, patients enrolled in these studies were required to have good performance status and some studies mandated limited weight loss. Some patients are also treated with lower doses of chemotherapy, particularly carboplatin and paclitaxel, concurrently with radiation followed by full-dose chemotherapy. Randomized studies have failed to show benefit of induction or consolidation chemotherapy. For patients who have a poor performance status or significant weight loss, a sequential approach of chemotherapy followed by radiation may be appropriate. Ongoing clinical trials are evaluating the utility of integrating some of the newer agents such as pemetrexed and cetuximab into the treatment plan for stage III patients.

Bevacizumab is currently approved for the treatment of several malignancies. Haematologic toxicities are not among the main concerns associated with bevacizumab, but they have been occasionally reported. We performed a meta-analysis to determine the incidence and risk of haematologic toxicities associated with bevacizumab.

The FDA's approval of bevacizumab for recurrent glioblastoma on May 9, 2009, was based on the significant response rate and clinical benefits seen from randomized phase II studies. Large-scale phase III data are unavailable. In an effort to determine benchmark efficacy parameters for bevacizumab and analyze its dose--response effect, the authors performed a meta-analysis of 15 studies published from 2005 to 2009, involving 548 patients with a median age of 53 years (range, 5-74 years), that used bevacizumab to treat recurrent glioblastoma. Median overall survival was 9.3 months (95% CI, 7.9-10.6 months). The respective 6-month progression-free and 6-month overall survival rates were 45% (95% CI, 34%-57%) and 76% (95% CI, 69%-84%), respectively. Median time to tumor progression was 6.1 months (95% CI, 4.2-8.1 months). The response analysis yielded a 6% complete response (95% CI, 2%-9%), 49% partial response (95% CI, 37%-61%), and 29% stable disease (95% CI, 20%-38%). No difference was seen in bevacizumab dose--response benefit between 5 mg/kg and 10 to 15 mg/kg. The efficacy benchmarks from this meta-analysis did not differ from those of the recently published randomized phase II studies. The lack of a dose--response effect would require confirmation in a prospectively conducted clinical trial.

Cyclophosphamide plus total body irradiation (CYTBI) and oral busulfan plus cyclophosphamide (BUCY) are commonly used conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with leukemia. However, there is conflicting data on the superiority of one regimen over the other. Our aim was to critically appraise and synthesize available evidence regarding the efficacy and safety of CYTBI compared to BUCY as a conditioning regimen.

The objectives of the present study are to investigate the efficacy and safety profile of gemcitabine-based combinations in the treatment of locally advanced and metastatic pancreatic adenocarcinoma (LA/MPC).

Standard treatment for high grade glioma (HGG) usually entails surgery (either biopsy or resection) followed by radiotherapy plus or minus temozolomide. Implanting wafers impregnated with chemotherapy agents into the resection cavity represents a novel means of delivering drugs directly to the resection cavity with potentially fewer systemic side effects. It is not clear how effective this modality is or whether it should be recommended as part of standard care for patients with HGG.