Sunitinib is a multitargeted tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST), and undergoing evaluation for other malignancy. Hypertension is one of its major side effects with a substantial variation in the reported incidences among clinical studies. We here performed a systematic review and meta-analysis of published clinical trials to determine its overall risk.

Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research.

Breast cancer subtyping and prognosis have been studied extensively by gene expression profiling, resulting in disparate signatures with little overlap in their constituent genes. Although a previous study demonstrated a prognostic concordance among gene expression signatures, it was limited to only one dataset and did not fully elucidate how the different genes were related to one another nor did it examine the contribution of well-known biological processes of breast cancer tumorigenesis to their prognostic performance.

Standard treatment for high grade glioma (HGG) usually entails biopsy or surgical resection where possible followed by radiotherapy. Systemic chemotherapy is usually only given in selected cases and its use is often limited by side effects. Implanting wafers impregnated with chemotherapy agents into the resection cavity represents a novel means of delivering drugs to the central nervous system (CNS) with fewer side effects. It is not clear how effective this modality is or whether it should be recommended as part of standard care for HGG.

Despite initial therapeutic success through androgen ablation in patients with advanced prostate cancer, the vast majority progress to androgen independence. Somatostatin (SST) analogs are a viable therapeutic modality before resorting to chemotherapy or immunotherapy. Their mechanism of action is related to a reduction in the IGF-1 (survival factor, reaction on neuroendocrine cells) appearing incrementally after long-term androgen deprivation and a possible suppression of GnRH receptors in prostate cancer following exposure to LHRH agonists.

This paper aims to evaluate the anti-emetic efficacy of cannabinoids in cancer patients receiving chemotherapy using a systematic review of literature searched within electronic databases such as PUBMED, EMBASE, PSYCINFO, LILACS, and 'The Cochrane Collaboration Controlled Trials Register'. Studies chosen were randomized clinical trials comprising all publications of each database until December 2006. From 12 749 initially identified papers, 30 fulfilled the inclusion criteria for this review, with demonstration of superiority of the anti-emetic efficacy of cannabinoids compared with conventional drugs and placebo. The adverse effects were more intense and occurred more often among patients who used cannabinoids. Five meta-analyses were carried out: (1) dronabinol versus placebo [n=185; relative risk (RR)=0.47; confidence interval (CI)=0.19-1.16]; (2) Dronabinol versus neuroleptics [n=325; RR=0.67; CI=0.47-0.96; number needed to treat (NNT)=3.4]; (3) nabilone versus neuroleptics (n=277; RR=0.88; CI=0.72-1.08); (4) levonantradol versus neuroleptics (n=194; RR=0.94; CI=0.75-1.18); and (5) patients' preference for cannabis or other drugs (n=1138; RR=0.33; CI=0.24-0.44; NNT=1.8). The superiority of the anti-emetic efficacy of cannabinoids was demonstrated through meta-analysis.

In advanced pancreatic cancer, level one evidence has established a significant survival advantage with chemotherapy, compared to best supportive care. The treatment-associated toxicity needs to be evaluated. This study examines the secondary outcome measures for chemotherapy in advanced pancreatic cancer using meta-analyses. A systematic review was undertaken employing Cochrane methodology, with search of databases, conference proceedings and trial registers. The secondary end points were progression-free survival (PFS)/time to progression (TTP) (summarised using the hazard ratio (HR)), response rate and toxicity (summarised using relative risk). There was no significant advantage of 5FU combinations vs 5FU alone for TTP (HR=1.02; 95% CI=0.85-1.23) and toxicity. Progression-free survival (HR 0.78; CI 0.70-0.88), TTP (HR=0.85; 95% CI=0.72-0.99) and overall response rate (RR=0.56; 95% CI=0.46-0.68) were significantly better for gemcitabine combination chemotherapy, but offset by the greater grade 3/4 toxicity thrombocytopenia (RR=1.94; 95% CI=1.32-2.84), leucopenia (RR=1.46; 95% CI=1.15-1.86), neutropenia (RR=1.48; 95% CI=1.07-2.05), nausea (RR=1.77; 95% CI=1.37-2.29), vomiting (RR=1.64; 95% CI=1.24-2.16) and diarrhoea (RR=2.73; 95% CI=1.87-3.98). There is no significant advantage on secondary end point analyses for administering 5FU in combination over 5FU alone. There is improved PFS/TTP and response rate, with gemcitabine-based combinations, although this comes with greater toxicity.

Erythropoiesis-stimulating agents (ESA) are approved for the treatment of anemia in patients with nonmyeloid malignancies whose anemia is due to the effect of concomitantly administered chemotherapy. Since the 1993 approval of epoetin alfa in patients with cancer, the risk of thrombovascular events, decreased survival, and poorer tumor control have been increasingly recognized. The risks of ESAs in patients with cancer and the design of trials to assess these risks have been the topic of discussion at two Oncologic Drugs Advisory Committees in 2004 and 2007.

Chemotherapeutic agents such as topotecan can be used to treat ovarian cancer. The effects of using topotecan as a therapeutic agent have not been previously been systematically reviewed.

Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied.

Intravascular devices (IVDs) carry significant risk of device-associated bloodstream infection (BSI). Catheter thrombosis increases the likelihood of microbial colonization of the catheter and BSI. Urokinase has been studied for the prevention of BSI associated with IVDs. We undertook a systematic review to determine the efficacy of urokinase-heparin lock or flush solution compared with heparin alone in preventing IVD-associated BSI.

Single-agent gemcitabine (GEM) is a standard treatment for advanced and metastatic pancreatic cancer. This study examines the question whether GEM-based combination chemotherapy can further improve treatment efficacy.

Mixed findings on the neuropsychological sequelae of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia (ALL), without radiation, indicate the need for a comprehensive meta-analytic review. The purpose of the current study was to conduct a meta-analysis assessing neuropsychological and academic functioning differences between children with ALL treated solely with chemotherapy and comparison groups.

Imatinib therapy for unresectable or metastatic gastrointestinal stromal tumour (GIST) is typically initiated at a dosage of 400mg/d. Two phase 3 studies investigated whether the higher dose of 800 mg/d - administered initially or upon progression on the 400-mg dose - would improve outcomes. Both the studies confirmed the 400mg/d starting dose for most patients. However, two groups benefited from the treatment with 800 mg/d of imatinib: patients with disease progression on standard-dose therapy, and patients whose tumour harbours an exon 9 mutation in KIT. Initial treatment with 800 mg/d of imatinib (400mg BID) should be considered for patients with KIT exon 9-mutant GIST. In unselected patients, dose optimisation to 800 mg/d may be warranted as a first step in managing progressive disease; such patients should be closely monitored.

Sorafenib is used in patients with advanced renal-cell carcinoma (RCC) or hepatocellular cancer, and its application in other types of cancers is also undergoing extensive clinical assessment. Hypertension is one of the major side-effects of this drug, and reported incidences vary substantially between clinical trials. We did a systematic review and meta-analysis of published clinical trials to establish the incidence of hypertension associated with sorafenib. The aim of this study is to gain a better understanding of the overall risk of hypertension in patients with cancer who receive sorafenib.

It was the aim of the review to determine the risks and benefits of primary thromboprophylaxis with anticoagulants in cancer patients with central venous devices. Medline, Central and Google Scholar databases were searched for randomized controlled trials (RCTs) in June 2006. Two reviewers extracted data and appraised the quality of RCTs. Results were expressed as relative risk (RR) with 95% confidence intervals (CI) using random effects model for the outcomes of catheter-related thrombosis, bleeding and thrombocytopenia. Eight RCTs (1,428 patients) were included. There was no statistically significant difference in the risk of catheter-related thrombosis for the use of warfarin versus placebo (3 trials, 425 patients, RR 0.75, 95% CI 0.24-2.35, p = 0.63), heparin versus placebo (4 trials, 886 patients, RR 0.46 95% CI 0.18-1.20, p = 0.06) or warfarin, unfractionated heparin or low-molecular-weight heparin versus placebo (7 trials, 1,311 patients, RR 0.59, 95% CI 0.31-1.13, p = 0.11). Substantial statistical heterogeneity was noted among these trials (I(2) > 50%). The use of anticoagulants showed no statistically significant difference in the risk of overall bleeding (5 trials, 1,193 patients, RR 1.24, 95% CI 0.84-1.82, p = 0.28), and thrombocytopenia for heparin versus placebo (4 trials, 958 patients, RR 0.85, 95% CI 0.49, 1.46, p = 0.55) without any statistical heterogeneity (I(2) = 0%). In cancer patients with central venous devices, thromboprophylaxis has no significant effect on the risk of catheter related thrombosis or bleeding. The use of primary thromboprophylaxis in cancer patients with central venous catheters while not causing any harm provides no benefit.

Hand-foot skin reaction (HFSR) is a dose-limiting toxicity associated with sorafenib, an oral multi-kinase inhibitor with clinical activity against solid tumors. This study was conducted to determine the risk of developing HFSR among patients receiving sorafenib.

The use of neoadjuvant chemotherapy in the treatment of locally advanced breast cancer is now well established. However, endocrine therapy can be a valid alternative to primary chemotherapy in the treatment of hormone-sensitive tumors, particularly in post-menopausal women. Tamoxifen (TAM) was initially used in older or frail patients who were not candidates for chemotherapy. Response rate of 49% to 68% were observed. These encouraging results prompted subsequent randomized phase III studies demonstrating the superiority of surgery in comparison to TAM as primary treatment. The successful use of aromatase inhibitors (AI) in the metastatic and adjuvant setting has encouraged studies that compare these agents with tamoxifen in the neoadjuvant setting. In terms of response rates, anastrozole and exemestane did not differ from TAM, while letrozole was superior. Nevertheless, all the AI were found to be superior to TAM as far as breast conserving surgery is concerned. The Americal College of Surgeons Oncology Group (ACOSOG) has recently activated a neoadjuvant randomized trial comparing anastrozole, letrozole and exemestane in postmenopausal patients with estrogen receptor positive tumors. Hopefully, this study will clarify which of these agents is more effective as primary endocrine therapy. In the meantime, neoadjuvant hormonal treatment should be considered in elderly patients with inoperable tumors or tumors not amenable to conservative surgery, with highly expressed estrogen receptors and contraindication to chemotherapy.

To assess the effect of adding interferon-alpha (IFN) +/- interleukin-2 (IL-2) to chemotherapy in patients with metastatic melanoma. METHODS A published data meta-analysis of trials of biochemotherapy versus chemotherapy in patients with metastatic melanoma was undertaken. End points evaluated were rates of partial response (PR), complete response (CR) and overall (partial + complete) response (OR); response duration; progression-free survival; overall survival (OS); and toxicity. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to whether IFN only or IFN and IL-2 were administered in the biochemotherapy arm.

The oncology community usually perceives phase I oncology trials as associated with poor or limited benefits and substantial risks. There is scarce data concerning outcome and survival of patients enrolled in current phase I oncology trials.