Tree nuts contain an array of phytochemicals including carotenoids, phenolic acids, phytosterols and polyphenolic compounds such as flavonoids, proanthocyanidins (PAC) and stilbenes, all of which are included in nutrient databases, as well as phytates, sphingolipids, alkylphenols and lignans, which are not. The phytochemical content of tree nuts can vary considerably by nut type, genotype, pre- and post-harvest conditions, as well as storage conditions. Genotype affects phenolic acids, flavonoids, stilbenes and phytosterols, but data are lacking for many other phytochemical classes. During the roasting process, tree nut isoflavones, flavanols and flavonols were found to be more resistant to heat than the anthocyanins, PAC and trans-resveratrol. The choice of solvents used for extracting polyphenols and phytosterols significantly affects their quantification, and studies validating these methods for tree nut phytochemicals are lacking. The phytochemicals found in tree nuts have been associated with antioxidant, anti-inflammatory, anti-proliferative, antiviral, chemopreventive and hypocholesterolaemic actions, all of which are known to affect the initiation and progression of several pathogenic processes. While tree nut phytochemicals are bioaccessible and bioavailable in humans, the number of intervention trials conducted to date is limited. The objectives of the present review are to summarise tree nut: (1) phytochemicals; (2) phytochemical content included in nutrient databases and current publications; (3) phytochemicals affected by pre- and post-harvest conditions and analytical methodology; and (4) bioactivity and health benefits in humans.

A systematic review and a meta-analysis were conducted, to investigate the possible association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with adverse effects related to methotrexate (MTX).

The authors address the question of whether vascular endothelial growth factor inhibitors (anti-VEGF) lead to better clinical outcomes than current treatments in patients with clinically manifest diabetic macular oedema (DMO), which is the leading cause of vision loss in the working age population in developed countries.

Neutropenia is a serious adverse event for patients who are treated with cetuximab, an inhibitor of endothelial growth factor receptor. However, there is no consistent result of the relationship between cetuximab and neutropenia in randomized controlled trials (RCTs). We did a systematic review and meta-analysis of published RCTs to assess the overall risk of neutropenia associated with cetuximab.

Pain in cancer patients remains common and is often associated with insufficient prescribing of targeted analgesia. An explanation for undertreatment could be the failure to identify neuropathic pain mechanisms, which require additional prescribing strategies. We wanted to identify the prevalence of neuropathic mechanisms in patients with cancer pain to highlight the need for detailed assessment and to support the development of an international classification system for cancer pain. We searched for studies that included adult and teenage patients (age above 12 years), with active cancer and who reported pain, and in which a clinical assessment of their pain had been made. We found 22 eligible studies that reported on 13,683 patients. Clinical assessment methods varied, and only 14 studies reported confirmatory testing for either sensory abnormality or diagnostic lesion to corroborate a diagnosis of neuropathic pain. We calculated that the prevalence of patients with neuropathic pain (95% confidence interval) varied from a conservative estimate of 19% (9.4% to 28.4%) to a liberal estimate of 39.1% (28.9% to 49.5%) when patients with mixed pain were included. The prevalence of pain with a neuropathic mechanism (95% confidence interval) ranged from a conservative estimate of 18.7% (15.3% to 22.1%) to a liberal estimate of 21.4% (15.2% to 27.6%) of all recorded cancer pains. The proportion of pain caused by cancer treatment was higher in neuropathic pain compared with all types of cancer pain. A standardised approach or taxonomy used for assessing neuropathic pain in patients with cancer is needed to improve treatment outcomes.

Epidermal growth factor receptor (EGFR) inhibitors, such as the monoclonal antibodies cetuximab and panitumumab, have proven efficacy in various types of cancer. However, these agents frequently result in skin toxicity, due to the expression of the EGFR in the skin. A correlation between the occurrence of skin toxicity and anti-tumor activity has been suggested in several phase III studies. However, since skin toxicity may impair the quality of life, and severe skin toxicity requires dose reduction or interruption, adequate and timely management of skin toxicity is important to maximize the anti-tumor efficacy of the EGFR inhibitor, as well as maintaining the patient's quality of life. Due to the small number of randomized controlled trials conducted in the field of EGFR inhibitor-induced skin toxicity so far, it is not possible yet to generate evidence based guidelines on its management. Here, we review and discuss available trials and case studies reporting on the management of EGFR inhibitor-induced skin toxicity.

There has been a significant shift within oncology drug development away from empiric screening of cytotoxic compounds to the era of genomics and molecularly targeted agents. The drug development process is evolving with greater emphasis on proof-of-mechanism studies in both preclinical and early clinical development. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Task Force, established as a forum for academic and pharmaceutical leaders to discuss methodological issues in targeted anticancer therapy development, met in March 2010 to review what were the minimal data required to make appropriate decisions about moving new targeted cancer agents from late preclinical development into phase I and from phase I into phase II trials. A number of specific questions were posed, and responses to each developed through survey, literature review and discussion at the face to face meeting of the MDICT Task Force. Consensus emerged around the necessity to demonstrate proof-of-mechanism and obtain information on key pharmacokinetic aspects of drug behaviour in late preclinical and early clinical trials. However, controversy remains on the extent of in vivo anti-tumour efficacy required to support clinical development of targeted agents. A systematic review of the data in this area would be informative. Further, while objective response in phase I trials may be a favourable signal about the potential activity of a new agent, debate exists around the weight that should be placed on the observation of stable disease or functional imaging changes in driving drug development decisions in the absence of observing either responses or convincing pharmacodynamic data in phase I. MDICT made a number of recommendations that may aid in future development of targeted agents.

The overall incidence and risk of nail changes associated with the use of epidermal growth factor receptor inhibitors (EGFRIs) varies widely across the literature.

Laetrile is the name for a semi-synthetic compound which is chemically related to amygdalin, a cyanogenic glycoside from the kernels of apricots and various other species of the genus Prunus. Laetrile and amygdalin are promoted under various names for the treatment of cancer although there is no evidence for its efficacy. Due to possible cyanide poisoning, laetrile can be dangerous.

Interferons alpha and beta have been used worldwide for a few decades, altering the natural history of several severe diseases including hepatitis C, cancer and immune-mediated conditions such as multiple sclerosis. The adverse events profile of interferons is well established, but only isolated reports of ophthalmological complications of interferon therapy have been published. The objective of this study was to carry out a literature systematic review on the subject, bringing to light the need for careful ophthalmological monitoring of patients undergoing interferon treatment. Nearly 500 cases of ophthalmological complications related to interferon have been reported. The most frequent findings were soft exudates, hemorrhages and retina ischemia.

We conducted a systematic review of the published literature to critically assess benefits and risks of the use of preoperative chemotherapy in patients presenting with colorectal liver metastases.

We conducted a systematic review and meta-analysis to dissect the association between PIK3CA mutations and resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) according to PIK3CA exon of mutations in metastatic colorectal cancer (mCRC).

During the last decade, the development of new drugs known as targeted therapies was the result of a better understanding of the processes involved in the transformation of normal cells into cancer. The term targeted therapy refers to drugs that selectively target specific molecular pathways involved in tumourigenesis or tumour progression. Angiogenesis is important for tumour growth and metastasis and is an important target for new biological agents. Bevacizumab is a humanised recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumour growth. On February 26, 2004, the FDA (Food and Drug Administration) approved Bevacizumab as first-line treatment for patients with metastatic colorectal cancer. The integration of targeted therapies in the treatment of colon cancer has resulted in significant improvements in efficacy outcomes. Bevacizumab was the first antiangiogenic therapy approved for use in cancer and received accelerated FDA approval for the treatment of recurrent glioblastoma multiform in 2009. The efficacy of Bevacizumab in the treatment of metastatic colorectal cancer and recurrent glioblastoma multiform is presented in this review article. The structural characteristics and selectivity profiles of this antiangiogenic drug and those disclosed in related patent applications are also summarised in this article.

In a previous systematic review and meta-analysis of five randomized controlled trials comparing rituximab maintenance with no maintenance (observation or rituximab at progression) for patients with follicular lymphoma, we reported that rituximab maintenance treatment improved the overall survival of patients. In this study, we did a similar search of the electronic databases updated through December 31, 2010, and included nine trials and 2586 follicular lymphoma patients. Hazard ratios (HRs) for time-to-event data were estimated and pooled using the inverse variance method. Risk ratios for dichotomous data were pooled using a fixed effect model. Patients treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.76, 95% confidence interval [CI] = 0.62 to 0.92) compared with patients in the no maintenance group. Patients with refractory or relapsed (ie, previously treated) follicular lymphoma treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.72, 95% CI = 0.57 to 0.91), whereas previously untreated patients had no survival benefit (pooled HR of death = 0.86, 95% CI = 0.60 to 1.25). The rate of infection-related adverse events was higher in the rituximab maintenance group (pooled risk ratio = 1.67, 95% CI = 1.40 to 2.00). These results further support the use of rituximab maintenance in the standard of care for refractory or relapsed follicular lymphoma.

Cetuximab (Erbitux*) is the only new medical therapy for locally and regionally advanced SCCHN to be licensed in industrialized countries in the past 15 years and presents an alternative to cisplatin which is the current therapeutic standard. In the absence of a published head-to-head trial, we estimated the relative benefit of cetuximab and cisplatin using an indirect comparison methodology.

Alemtuzumab is a humanized monoclonal antibody that recognizes the CD52 antigen expressed on malignant and normal B lymphocytes. It has come to be used therapeutically in B-cell malignancies and, in addition, it shows interesting activity also in T-cell lymphomas. Published literature and abstract proceedings were scanned, and a systematic review of phase II studies administering alemtuzumab in patients with T-cell lymphomas was performed. Alemtuzumab is an effective alternative option for patients with peripheral T-cell lymphomas and cutaneous T-cell lymphomas. Alemtuzumab may belong to the current standard of care for nodal and cutaneous T-cell lymphomas.

To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology.

To assess the role of the novel second-line treatments in nonsmall cell lung cancer (NSCLC).

Breast cancer is the most common cancer affecting women in the UK. Tamoxifen (TAM) is considered as the standard of care for many women with oestrogen receptor positive breast cancer. However, wide variability in the response of individuals to drugs at the same doses may occur, which may be a result of interindividual genetic differences (pharmacogenetics). TAM is known to be metabolised to its active metabolites N-desmethyl TAM and 4-hydroxytamoxifen by a number of CYP450 enzymes, including CYP2D6, CYP3A4, CYP2C9, CYP2C19 and CYP2B6. N-desmethyl TAM is further metabolised to endoxifen by CYP2D6. Endoxifen, which is also formed via the action of CYP2D6, is 30- to 100-fold more potent than TAM in suppressing oestrogen-dependent cell proliferation, and is considered an entity responsible for significant pharmacological effects of TAM. Thus, an association between the cytochrome P450 2D6 (CYP2D6) genotype and phenotype (expected drug effects) is believed to exist and it has been postulated that CYP2D6 testing may play a role in optimising an individual's adjuvant hormonal treatment.

Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity.