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At present three erythropoietic-stimulating agents (ESAs) are available, these being epoietin alpha, epoietin beta and darbepoietin. In oncology the marketing licence given in the early 1990s was and still is for reduction of red blood cell (RBC) transfusion in chemotherapy-induced anaemia (CIA) in non-haematological neoplasia. Regulatory bodies as well as various scientific societies have issued guidelines and updated these regularly in accordance with additional data from numerous studies published since first marketing. Over the past few years, worrisome data have shown adverse effects in trials comparing ESAs with controls (transfusion or placebo). In fact reviewing the published literature closely does not allow at the time of writing (March 2008) the exclusion of a survival decrease due to an effect of ESAs on the cancer itself. Haemoglobin (Hb) target dosing has been an issue and is addressed in the dosing of ESAs in patients on therapy. In addition to survival and tumour progression, published articles also address at length thromboembolic diseases (TEDs), these being more frequent in ESA-treated patients compared with the controls in various studies. The three agents epoietin alpha, epoietin beta and darbepoietin can be considered as the same pharmacological class as regards indications of CIA, Hb limits and dose adjustments, as well as regards warnings in respect of adverse effects. The purpose of this paper is not to to be a substitute for recommendations or official recently published guidelines (ASCO, ASH, ESMO, EORTC, NCCN, etc.) but to present an overview of the data which have motivated ongoing regulatory authorities’ assessments and reviewing of guidelines. An updated Cochrane review is underway, and the regulatory authorities such as the Food and Drug Administration (FDA) after the recent ‘Oncology drug advisory committee to the FDA’ (ODAC) of March 15, 2008, and the EMEA will most probably refine the present safety recommendations. Various aspects and adverse effects are to be considered here. (i) The realization that TED is a major issue in routine treatment. (ii) The fact that several studies have shown progression of disease and/or decreased survival in the ESA-treated group of patients compared with controls. Erythropoietin receptor (EpoR) data on malignant cells from a ‘Head and Neck Cancer’ trial with radiotherapy treatment and a target Hb beyond 14 g/ dl have been and still are largely commented on in the medical literature [1]. (iii) Furthermore, quality of life (QoL) has been considered as an additional benefit of ESA therapy, and the latest analyses cast doubts on the validity of this presumed benefit [2].

nGlaxo Research and Development Limited, Greenford, Middlesex, U.K. Summary Background: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O+D) with metoclopramide plus dexamethasone plus lorazepam (M+D+L) over three consecutive courses of cisplatin chemotherapy. Patients and methods: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4mg bd orally. M + D+L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M+D+L). Results: On the first course of chemotherapy, O + D was significantly superior to the M+D+L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P" 0.014). This was maintained over the three treatment cycles; 38% of O+D and 20% of M+D+L patients remained free of emesis (P — 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O+D group (48%) than in the M+D+L (26%, P - 0.003). The most commonly occurring adverse events in the O+D group were constipation (25%) and headache (19%). In the M+D+L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M+D+L group. Despite the inclusion of lorazepam, 14% of patients in the M+D+L group were withdrawn from the study due to extrapyramida l symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. Conclusion: This study shows that O+D is significantly more effective and better tolerated than M+D+L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.

International audience; Knowledge of the biology and management of rectal cancer continues to improve. A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is mandatory, to assure optimal diagnosis and staging, surgery, selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management. Moreover, optimal symptom management also requires a dedicated team of health care professionals. The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery. High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control. There are now randomized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting. Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy. Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer. New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority. Those involved in the care for patients with rectal cancer should be encouraged to participate in well-designed clinical trials, to increase the evidence-based knowledge and to make further progress. Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise.

Arterial thrombosis is not a specific cancer related disorder except in some patients on some antiangiogenic drugs, but remains an infrequent event compared to venous thromboembolism (VTE). VTE is the second most frequent cause of death in cancer patients and is a predictor of mortality in hospitalized cancer patients. The death rate is about 30% in cancer patients when VTE occurs within 3 months of diagnosis. About 15% of patients suffering from cancer will have a VTE during the course of their disease and about 10% of patients with an idiopathic (?) VTE develop a cancer in the following two years. Risk factors for VTE in oncology are patient dependent, treatment dependent, type of cancer and stage dependent, The pathophysiology of VTE is complex. In addition to the standard causes, biomarkers and a clinical risk assessment score can be useful in deciding on time and duration of VTE prophylaxis and treatment. Prophylactic treatment in the ambulatory cancer patient needs to be discussed as newer anticoagulants like ultra low molecular weight heparin have been used recently in clinical trials and other novel agents (dabigatran, rivaroxaban and apixaban) marketed for orthopedic surgery and atrial fibrillation have become routine. The latter drugs are given orally, have negligeable interference with other medications or with foodstuffs and do not need laboratory surveillance. Approval for market release in VTE therapy in the general medical situation is pending and will certainly be used in the oncological setting if cost compatible. Various guidelines (ESMO, ASCO, NCCN …) are concurrent in their recommendations depending on disease activity, anti-cancer treatments (surgery, chemotherapy …) and the patient's clinical situation. These will be discussed in regards to the ambulatory and hospitalized patient, for first episode and for recurrent VTE. Some data are available though not presently recommended, for anticoagulant therapy in oncology for improving survival. Disclosure The author has declared no conflicts of interest.

Introduction In order to evaluate various SNP's in different genes and chromosomal locations in Caucasian patients as markers of the predisposition to the colorectal cancer (CRC) disease, we analyzed the frequency of different tumour-associated single-nucleotide polymorphisms in several genes including p53 and SMAD7 of Caucasian CRC patients as compared to a healthy Caucasian control population. Methods Tumour samples were obtained from 188 CRC patients at the adenocarcinoma stage and from 98 healthy control individuals. After gDNA extraction, selected amplicons were amplified by PCR, followed by melting curve analysis. The statistical evaluation of the difference in genotype frequency at the different SNPs comparing CRC patients with healthy controls was carried out using the Chi-squared test. Results When analyzing 188 tumour samples and comparing with 98 healthy controls, a significant difference in the genotype distribution of the G429C SNP in the p53 gene was observed (P = 0.046). Similarly, a significant difference was found for rs4939827 C > T in the SMAD7 gene (P = 0.037), although no significant differences were found for rs4464148 T > C (P = 0.585) or rs12953717 C > T (P = 0.197) also in SMAD7. Differences in genotype distribution for CHR9 C > A rs719725 and CHR8 G > A rs7014346 were almost significant (P = 0.050 and P = 0.054 respectively). Significant results previously reported for two other genes were confirmed:- PAI, 5G vs. 4G, rs1799899 (P = 0.047) and TGFBR1 A > G rs334348, G > A rs334349 and A > C rs1591 (P Conclusion The results for p53, SMAD7, PAI, CHR8 and CHR9 are suggestive rather than conclusive and invite confirmation through further study. Concerning the association between the TGFBR1 SNP's and colorectal cancer, on the other hand, the results are already clear. For example, with the TGFBR1 SNP rs334348, the frequency of the GG genotype was as much as 43% for the CRC patients but 11% for the controls, while the frequency of the AA genotype was only 18% for the patients and 43% for the controls. Adding further markers like SNPs for SMAD7, PAI, CHR8 and CHR9 is not significant, p53 though statistically borderline (P = 0.046) does not add clinical relevance.