The antiemetic efficacy of haloperidol was studied using data from 15 published (1962-1988) and 8 unpublished randomized trials; 1,397 adults received haloperidol, and 1,071 were controls. Settings were postoperative nausea or vomiting (1,994 patients), gastroenterology (261), chemotherapy (189), and radiation therapy (24). The relative benefit to prevent postoperative nausea or vomiting during 24 h with 0.5-4 mg haloperidol compared with placebo was 1.26-1.51 (number needed to treat, 3.2-5.1), without evidence of dose responsiveness; 0.25 mg was not antiemetic. With 1 mg haloperidol, the relative benefit to stop postoperative nausea or vomiting during 2-4 h compared with placebo was 1.53 (95% confidence interval, 1.17-2.00; number needed to treat, 6); with 2 mg, the relative benefit was 1.73 (1.11-2.68; number needed to treat, 4). In gastroenterology, 2 mg haloperidol was more effective than 1 mg. For chemotherapy and radiation therapy, no conclusions could be drawn. With 4 mg, one patient had extrapyramidal symptoms. With 5 mg, sedation was increased, with a relative risk of 2.09 (95% confidence interval, 1.73-2.52; number needed to treat, 4.4). There were no reports on cardiac toxicity. Postoperatively and in gastroenterology, haloperidol is antiemetic, with minimal toxicity. For other clinical settings and for children, valid data are unavailable.

In the past, cancer patients entering phase 1 studies confronted the prospects of high risk and unlikely benefit. Over the last decade, cancer drugs under development have become more targeted, and the clinical research environment has become more scrutinized. The impact of these changes on the risks and benefits to patients who participate in phase 1 cancer trials is unknown.

The superiority of Fludarabine over conventional therapy as primary induction therapy for patients with chronic lymphocytic leukemia (CLL) has been shown in several studies but no studies have yet reported a pooled estimate of the treatment effect. We performed a systematic review of evidence from 5 randomized controlled trials involving approximately 1300 patients with CLL, comparing Fludarabine with several alkylator-based combination regimens in the primary treatment of CLL. Complete response rate was significantly higher for Fludarabine compared to alkylator-based chemotherapy (RR 1.87, 95% CI 1.10-3.19, P=0.02), while overall response, though superior, did not reach statistical significance (RR 1.22, 95% CI=0.88-1.69, P=0.24). Overall survival was similar for Fludarabine and alkylator-based therapy (the pooled log hazard ratio of death, HR=-0.05, 95% CI=-0.36-0.26, P=0.75). Infection rate was significantly higher (RR 1.58, 95% CI=1.10-2.27, P=0.01), but there was no significant difference in the incidence of thrombocytopenia, neutropenia and anemia. Therefore, this meta-analysis supports the findings that Fludarabine as an induction agent for patients with CLL yields a better clinical response with acceptable toxicity when compared with alkylator-based combination therapy, but without a survival benefit by 5-6 years of follow up.

Antitumour antibiotics are used in the management of metastatic breast cancer. Some of these agents have demonstrated higher tumour response rates than non-antitumour antibiotic regimens, however a survival benefit has not been established in this setting.

To assess the overall risk of stroke, specifically ischemic stroke, associated with tamoxifen use by performing a meta-analysis of data reported in breast cancer trials.

Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST.

The modulation of fluorouracil (FU) by folinic acid (leucovorin [LV]) has been shown to be effective in terms of tumor response rate in patients with advanced colorectal cancer, but a meta-analysis of nine trials previously published by our group failed to demonstrate a statistically significant survival difference between FU and FU-LV. We present an update of the meta-analysis, with a longer follow-up and the inclusion of 10 newer trials.

The purpose of this study was to identify patient characteristics that may be risk factors or markers of susceptibility to adverse treatment effects in cancer Phase I and II clinical trials.

Granulopoiesis-stimulating factors, such as granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF), are being used to prevent febrile neutropenia and infection in patients undergoing treatment for malignant lymphoma. The question of whether G-CSF and GM-CSF improve dose intensity, tumour response, and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive, a systematic review was undertaken.

Hepatocellular carcinoma (primary liver cancer) is the third commonest cause of cancer mortality world-wide. Survival is poor for patients with advanced disease. Trials of tamoxifen for hepatocellular carcinoma have conflicting results.

1) To characterize the population pharmacokinetics of apomine in healthy males and in male and female patients with solid tumours and 2) to understand more fully the influence of induction and between- and within-subject variability on exposure to drug using Monte Carlo simulation.

High-dose methotrexate (HDMTX)-induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX-induced nephrotoxicity has been managed with high-dose leucovorin, dialysis-based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase-G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX-induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis-based methods of MTX removal with treatment using CPDG2.

Oral mucositis (OM), an inevitable side effect of almost all anti-cancer treatments, affects the patient's physiological functions and their psychological well being. In spite of numerous treatment modalities for this condition, there is still a lack of evidence-based clinical trials that can provide a single efficient pharmacologic agent or intervention for either prevention or treatment of OM. This study analyses and summarizes some of the more "accepted" modalities for treatment of OM. It is recommended that these modalities rely on simple, convenient and innocuous interventions, which should be adjusted for each individual complaint. Well-designed, controlled and standardized studies are necessary to validate effectiveness of available, as well as newly developed interventions for OM.

Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used to prevent febrile neutropenia and infections in the treatment of patients with malignant lymphoma. The question whether G-CSF and GM-CSF improve dose-intensity, tumour response and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive a systematic review was required.

We performed a systematic review of the effectiveness of anti-emetics for prophylaxis of cisplatin-induced delayed emesis using meta-analysis. We selected 12 reports of randomized controlled trials from MEDLINE (1966-2003. 4) and The Cochrane Library Issue 1, 2003. Nine of these reports were evaluated as high quality and the others as low quality according to the evaluation criteria of Jadad et al., and only the high-quality reports were subjected to meta-analysis. The statistical results obtained from all 12 reports were also compared with those obtained from the 9 reports of high quality. Corticosteroids significantly reduced the occurrence of delayed emesis. Metoclopramide tended to reduce the occurrence of delayed emesis, although not to a significant extent. In contrast, 5-HT3 receptor antagonists did not show a significant prophylactic effect on delayed emesis. Combination treatments using corticosteroids with metoclopramide or 5-HT3 receptor antagonists did not show significant additional benefits over corticosteroids alone. In conclusion, treatment with corticosteroids without additional metoclopramide or 5-HT3 receptor antagonists appears to be preferable for the prevention of delayed emesis induced by cisplatin.

Several cases of cardiac adverse reactions related to vinorelbine (VNR) have been reported in the literature. In order to quantify the incidence of these cardiac events, we performed a meta-analysis of clinical trials comparing VNR with other chemotherapeutic agents in the treatment of various malignancies. Randomized clinical trials comparing VNR with other drugs in the treatment of cancer were searched in Medline, Embase, Evidence-based Medicine Reviews databases and the Cochrane library from 1987 to 2002. Outcomes of interest were severe cardiac events, toxic deaths and cardiac event-related deaths reported in each publication. We found 19 trials, involving 2441 patients treated by VNR and 2050 control patients. The incidence of cardiac events with VNR was 1.19% [95% confidence interval (CI) (0.75; 1.67)]. There was no difference in the risk of cardiac events between VNR and other drugs [odds ratio: 0.92, 95% CI (0.54; 1.55)]. The risk of VNR cardiac events was similar to vindesine (VDS) and other cardiotoxic drugs [fluorouracil, anthracyclines, gemcitabine (GEM) em leader ]. Even if it did not reach statistical significance because of a few number of cases, the risk was lower in trials excluding patients with cardiac history, and seemed to be higher in trials including patients with pre-existing cardiac diseases. Vinorelbine-related cardiac events concern about 1% of treated patients in clinical trials. However, the risk associated with VNR seems to be similar to that of other chemotherapeutic agents in the same indications.

A meta-analysis was conducted to evaluate possible neuropsychological effects of treatments for cancer in adults. A search revealed 30 studies, encompassing 29 eligible samples, and leading to inclusion of a total of 838 patients and control participants. A total of 173 effect sizes (Cohen's d) were extracted across 7 cognitive domains and as assessed in the literature via 3 methods of comparison (post-treatment compared with normative data, controls, or baseline performance). Statistically significant negative effect sizes were found consistently across both normative and control methods of comparison for executive function, verbal memory, and motor function. The largest effects were for executive function and verbal memory normative comparisons (-.93 and -.91, respectively). When limiting the sample of studies in the analyses to only those with relatively "less severe" diagnoses and treatments, the effects remained. While these results point toward some specific cognitive effects of systemic cancer therapies in general, no clear clinical implications can yet be drawn from these results. More research is needed to clarify which treatments may produce cognitive decrements, the size of those effects, and their duration, while ruling out a wide variety of possible mediating or moderating variables.

Recent studies have reported improved survival with concurrent chemoradiotherapy (ChRT) for inoperable non-small-cell lung cancer (NSCLC). ChRT includes the delivery of low-dose chemotherapy given daily during radiotherapy (RT) or higher doses administered weekly. It remains unknown whether a difference in efficacy or toxicity exists between these approaches. A systematic review was performed to compare the efficacy and toxicity of weekly vs. daily ChRT.

Tamoxifen reduces the risk of developing breast cancer but also affects the risks of certain vascular and neoplastic events. Our purpose was to estimate the effects of tamoxifen on potentially life-threatening vascular and neoplastic outcomes.

The relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and the risk of gastric cancer has not been well studied. We performed a systematic review and meta-analysis of published studies to evaluate the association between use of this class of drugs and the risk of gastric cancer.