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).

To identify which neuropsychological tests have been used to evaluate chemotherapy-induced impairment in various domains of cognitive function in patients with breast cancer and to determine the sensitivity of each of the tests through estimation of effect size.

Benefits of prophylactic hematopoietic colony-stimulating factors (CSFs) in adults and children receiving cancer chemotherapy or undergoing stem-cell transplantation (SCT) are unclear.

To characterise the population pharmacokinetics of trabectedin (ET-743, Yondelis(R)) in cancer patients.

To estimate the efficacy of third-generation (3G) chemotherapy agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan) on response and survival in stage IIIB/IV non-small cell lung cancer (NSCLC).

To systematically review the research evidence on the effectiveness of hypnosis for cancer chemotherapy-induced nausea and vomiting (CINV). A comprehensive search of major biomedical databases including MEDLINE, EMBASE, ClNAHL, PsycINFO and the Cochrane Library was conducted. Specialist complementary and alternative medicine databases were searched and efforts were made to identify unpublished and ongoing research. Citations were included from the databases' inception to March 2005. Randomized controlled trials (RCTs) were appraised and meta-analysis undertaken. Clinical commentaries were obtained. Six RCTs evaluating the effectiveness of hypnosis in CINV were found. In five of these studies the participants were children. Studies report positive results including statistically significant reductions in anticipatory and CINV. Meta-analysis revealed a large effect size of hypnotic treatment when compared with treatment as usual, and the effect was at least as large as that of cognitive-behavioural therapy. Meta-analysis has demonstrated that hypnosis could be a clinically valuable intervention for anticipatory and CINV in children with cancer. Further research into the effectiveness, acceptance and feasibility of hypnosis in CINV, particularly in adults, is suggested. Future studies should assess suggestibility and provide full details of the hypnotic intervention.

Recent clinical trials showed that gemcitabine (GEM) of fixed-dose rate infusion has certain effect on advanced pancreatic cancer. Some meta-analyses suggest that GEM plus cisplatin (DDP) or its analogues is better than GEM alone in treating advanced pancreatic cancer. This study was to evaluate the efficacy of GEM of fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as first-line therapy for advanced pancreatic cancer by meta-analysis.

While head-to-head clinical trials demonstrate pegfilgrastim to be as efficacious as filgrastim in reducing chemotherapy-induced neutropenia, these studies lacked the statistical power to demonstrate better outcomes with one therapy compared to the other. Our objective was to obtain a pooled estimate of the effect of pegfilgrastim compared with filgrastim on incidence of febrile neutropenia (FN), and related outcomes among patients with solid tumors and malignant lymphomas receiving myelosuppressive chemotherapy.

A meta-analysis of chemotherapy for glioblastoma multiforme (GBM) was performed. We sought to update prior analyses by focusing exclusively on GBM, including new trials of novel treatments, assessing effectiveness of individual treatment categories and presenting data in a clinically useful format.

Statins have been suggested to prevent colorectal cancer. Several epidemiologic studies have evaluated this association, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature.

In five randomized clinical trials (RCTs), adjuvant trastuzumab (T) for early stage breast cancer with human epidermal growth-factor receptor-2 over-expression/gene-amplification has shown to decrease the risk of both recurrence and death. The issue regarding the long-term safety profile of such drug is still open; in particular, questions remain about long-term cardiotoxicity, and specific patterns of relapse such as brain metastases (BM). In order to quantify the magnitude of these two risks, and then balance those with the survival outcome, a literature-based meta-analysis was performed.

Although aggressive dose escalation strategies were designed to improve the risk-benefit profile of phase 1 oncology trials, they have not been adequately studied. The prevalence of several novel trial designs and their association with a variety of clinical endpoints was evaluated.

Myelosuppression was found to be one of the main toxicities of trabectedin (ET-743, Yondelis) during phase I/II studies. Our objective was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model that describes the time course of the absolute neutrophil counts (ANCs) in cancer patients receiving trabectedin. Data from 699 patients who received intravenous trabectedin as monotherapy (dose range: 0.006-1.8 mg/m2) as a 1-, 3-, or 24-h infusion every 21 days; 1- or 3-h infusion on days 1, 8, and 15 every 28 days; or a 1-h infusion daily for 5 consecutive days every 21 days were used to develop (N=405; ANCs=7,291) and validate (N=294; ANCs=5,029) the model. The PK/PD model comprised a trabectedin-sensitive progenitor cell compartment, linked to the peripheral blood compartment, through three transition compartments representing the maturation chain in the bone marrow. To capture the rebound effect due to endogenous growth factors, the model included a feedback mechanism. The model estimated three system-related parameters: ANC at baseline (Circ0), mean transit time in bone marrow (MTT), and a feedback parameter (gamma). A first-order process quantified by the rate constant k(e0) described the trabectedin concentrations at the effect compartment (C(e)), which were assumed to reduce the proliferation rate and/or to increase the killing rate of the progenitor cells according to the function alphaC(e)beta. The model was qualified and simulations were undertaken to evaluate the neutropenia schedule dependency and the effects of selected covariates. NONMEM software was used to perform the modeling and simulation analyses. For a typical man of 70 kg, the mean values (between-subject variability; %) of the Circ0, MTT, gamma, k(e0), alpha, and beta were estimated to be 4.46 x 10(9)/l (37.9%), 4.0 days (37.5%), 0.218 (41.8%), 2.09 h(-1) (77.9%), 2.00 l/microg (85.1%), and 1.26, respectively. Although in women, k(e0) was reduced by 29% and a 25% increase in body weight resulted in a 12.6% reduction in the beta parameter, the clinical relevance of these effects is limited. The model evaluation procedure indicated accurate prediction of the observed incidence of neutropenia grades 3 and 4 across the dosing regimens evaluated. Simulations indicated that trabectedin dose and interdose interval, but not infusion duration, are the main determinants of the neutropenia severity. The model-predicted time course of the ANC and its variability confirmed that neutropenia is reversible, of short duration, and non-cumulative. The extent and time course of neutropenia following six different dosing regimens of trabectedin were well predicted by the semiphysiological PK/PD model.

This meta-analysis compares the feasibility, safety and clinical outcome of long-term therapy with topotecan vs. standard treatment duration in patients with recurrent ovarian cancer.

The aim of this study was to assess the efficacy of currently available topical drugs for vernal keratoconjunctivitis (VKC) through a meta-analysis of randomised clinical trials (RCTs).

With the increase in the number of reports and trials on the use of thalidomide as a part of the treatment of different medical conditions, particularly multiple myeloma (MM), it was observed that this drug might be associated with an increase in the risk of venous thromboembolic (VTE) events. It was the objective of this study to assess this risk, to check whether it might be affected by the concomitant administration of other medications, specifically dexamethasone, and to study the effect of anticoagulation and anti-platelet medications. A literature search for articles describing the use of thalidomide and the resultant VTE events was performed, and 50 articles were reviewed. A sample consisting of 3,322 patients resembling the above-mentioned studies was designed, and multivariate logistic regression was conducted. While thalidomide, dexamethasone and their combination were found to significantly increase the risk of VTE events among MM patients by 2.6, 2.8 and eight times, respectively, "adequate" anticoagulation significantly reduced the risk. In conclusion, patients receiving thalidomide should be carefully monitored for thromboembolic events, and those receiving concomitantly dexamethasone or other chemotherapy should be followed even more closely. Administering prophylactic doses of low-molecular-weight heparin or warfarin with therapeutic International Normalized Ratio reduces the risk of thromboembolic events among MM patients.

Ovarian cancer is the fourth leading cause of cancer death among women in the United States. First-line chemotherapy offered to patients with ovarian cancer generally consists of an intravenous (IV) platinum plus taxane regimen and has remained virtually unchanged for the past 10 years. A number of recently completed phase III randomized trials in the United States have reported improved progression-free survival (PFS) and/or overall survival (OS) with the intraperitoneal (IP) administration of cisplatin. The purpose of this study was to pool the published data to perform a meta-analysis of randomized trials of IP cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This study was initiated to obtain a more valid estimate of the therapeutic impact of IP treatment for these patients. A search strategy was initiated that searched published findings of randomized trials of IP cisplatin therapy from multiple sources from January 1990 through January 2006. Six randomized trials of 1716 ovarian cancer patients were identified and included in this analysis. The pooled hazard ratio (HR) for PFS of IP cisplatin as compared to IV treatment regimens is 0.792 (95% CI: 0.688-0.912, P= 0.001), and the pooled HR for OS is 0.799 (95% CI: 0.702-0.910, P= 0.0007). These findings strongly support the incorporation of an IP cisplatin regimen to improve survival in the front-line treatment of stage III, optimally debulked ovarian cancer.

Short term side-effects of chemotherapy include fatigue, nausea, vomiting, mucositis and myelosuppression or neutropenia. These occur during the course of treatment and generally resolve within months of completion of chemotherapy. A variety of Chinese medicinal herbs have been used for managing these side effects.

The introduction of monoclonal antibodies (MoAbs) into the treatment of cancer has led to improvements in patient survival. However, to the authors' knowledge, little attention has been paid to the infectious complications associated with their use. The authors performed a systematic review of the literature to identify randomized controlled trials (RCTs) that included in their outcomes a comparison of the infectious complications of a MoAb plus chemotherapy or radiotherapy versus the therapy regimen given without the addition of a MoAb. Twenty RCTs with relevant data regarding the use of MoAbs in patients with hematologic malignancies (10 RCTs) and solid tumors (10 RCTs) were retrieved. Six RCTs compared rituximab in conjunction with the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus CHOP alone for the treatment of B-cell non-Hodgkin lymphoma (NHL). No significant increase in the incidence of infections was observed with the addition of rituximab to chemotherapy (based on data from 5 RCTs). However, in patients who were seropositive for the human immunodeficiency virus (HIV), a 12% increase in infection-related deaths and a rate of higher opportunistic infections was associated with the rituximab-containing regimen (data taken from 1 RCT). Five RCTs either compared trastuzumab plus chemotherapy versus chemotherapy alone or trastuzumab monotherapy versus observation in patients with breast cancer. The addition of trastuzumab to the various chemotherapy regimens was found to cause a slight increase in the frequency of high-grade infections while bevacizumab caused a negligible increase in Grade III/IV infections compared with the same regimens given of chemotherapy alone. Based on a single trial, a higher comparable increase in the rate of high-grade infections was noted with the use of cetuximab in addition to chemotherapy compared with chemotherapy alone. MoAbs added to chemotherapy appear to have infectious complications that are comparable to the chemotherapy-alone regimen when administered for the treatment of NHL, with the exception of HIV-seropositive patients. Trastuzumab, which is reported to have a clear benefit in the prognosis of breast cancer patients, was found to cause a small increase in Grade III/IV infectious complications; however, there was no apparent difference in the rate of infection-related death.

The purpose of this study was to examine the efficacy of a combination treatment of sequential irinotecan and doxifluridine, an intermediate of capecitabine, evaluated by the response rate and safety in patients with metastatic colorectal cancer. In all, 60 metastatic colorectal cancer patients with measurable disease were enrolled. The schedule of the treatment consisted of a 90 min intravenous (IV) infusion of irinotecan 150 mg/m2 for on days 1 and 15, and 600-1,000 mg/body of oral doxifluridine on days 3-14 and 17-28. Cycles were repeated every 35 days. A median of three cycles of the combination therapy (range 1-14 cycles) was administered. A total of 57 patients (95%) completed at least two cycles of the therapy without any dose reductions. There was one complete response and 23 partial responses with an overall response rate of 40% [95% confidence interval (CI): 28-53%]. A total of 19 patients had stable disease, 43(72%) achieved disease control. The median time to progression was 5.9 months and the median overall survival was 20.5 months. Ten (17%) and 17 (28%) patients developed Grade 3-4 leukopenia and neutropenia, respectively. Grade 3-4 fatigue was observed in 7(12%) patients, nausea in five (8%), vomiting in four (7%), and diarrhea,in three (5%) patients. No treatment-related deaths were noted during the study. From these results, the combination of sequential irinotecan and doxifluridine is considered to be an effective, easy-to-administer regimen with acceptable tolerability.