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.

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.

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.

Anthracyclines reduce myocardial repolarization reserve and might increase the risk for Torsades de Pointes a long time after treatment. We studied all the publications concerning Torsades de Pointes in patients previously treated with anthracyclines to investigate the clinical circumstances leading to this rare life-threatening complication. Our literature search yielded nine reports of 11 patients who had developed Torsades de Pointes anywhere from weeks to years following treatment with anthracyclines. One of the patients was hospitalized in our medical center. Risk factors and triggers for Torsades de Pointes, among other clinical aspects, were analyzed in each report. Most patients (n=10; 90.9%) were previously treated with anthracyclines owing to acute leukemias: acute myelogenous leukemia (n=5), acute lymphocytic leukemia (n=3) and acute promyelocytic leukemia (n=2). One patient was previously treated with anthracyclines owing to Hodgkin's lymphoma. Most patients were women (n=9; 81.8%). The most prevalent triggers for Torsades de Pointes were the administration of a QT-prolonging agent (n=10; 90.9%) and hypokalemia (n=9; 81.8%). Azole derivatives were the most prevalent of the QT-prolonging agents that triggered Torsades de Pointes (n=5; 45.5%). Although four patients suffered from anthracycline-induced left ventricular dysfunction and five other patients had only one or two questionable triggers for Torsades de Pointes, in only two of these cases the authors considered previous treatment with anthracyclines as a risk factor for Torsades de Pointes. Previous treatment with anthracycline is an underestimated risk factor for Torsades de Pointes. Possible triggers includes azole derivatives, other QT-prolonging agents and hypokalemia. Women patients are particularly at risk.

This meta-analysis examines a wide range of small molecule anticancer drugs to search for a structure common to all. Although they encompass a very wide range of structures, nearly all reveal the presence of an allylic O, N, or S atom. In some, the allylic oxygen is a carbonyl group, or an alcohol group, which can be substituted (ester, lactone, glycoside, ether) or replaced by an amino or imino nitrogen Some antineoplastic drugs do not exhibit this moiety but are converted in vivo to allylic derivatives. An allylic hydroxyl is also present in most sphingolipids, ubiquitous body components that control proliferative and anti-proliferative cell functions. Ceramide, the precursor of all the allylic sphingolipids, seems to be a general inducer of apoptosis in cancer cells. Further examination of sphingolipids and anticancer drugs shows the frequent occurrence of [i] double bonds conjugated to the allylic bond, (ii) two or more allylic moieties in each molecule, (iii) lipophilic features, especially linear chains, and (iv) attachment of an O, N, or S atom to a carbon atom of the allylic double bond, e.g., -CH(2)-C(OMe)=CH-CH(OH)-CH(2)-. Suggested mechanisms of action: (a) allylic ketone drugs undergo a Michael condensation with tumor thiols or other reactive groups; (b) allylic OH drugs undergo oxidation to an allylic ketone, generating reactive oxygen; (c) some interfere with mitochondrial ubiquinone, blocking ATP production; (d) some act as a ceramide mimic (inhibitor or agonist) in ceramide-controlled kinases, phosphatases, and proteases; (e) many antineoplastic drugs stimulate ceramide-forming processes.

Given that the efficacy/safety of thalidomide for relapsed or refractory multiple myeloma have not been well characterized in a randomized, controlled setting, an analysis of larger, single-agent trials was conducted. Nine trials met the following inclusion criteria: primary population of multiple myeloma; all patients relapsed or refractory; single-agent thalidomide; and sample size > or =50. At median doses of 200 - 800 mg per day, the pooled overall response rate (ORR) was 28.2% (95% CI: 22.6 - 33.7%), including a complete response (CR) rate of 1.6% (95% CI: 0.3 - 2.9%) and partial response rate of 26.0% (95% CI: 20.1 - 32.0%). Response was typically based on M-protein reduction alone. Peripheral neuropathy (PN) incidence varied from 12 - 44%, possibly impacted by the short median follow-up (9 - 29 months). Pooled venous thromboembolism (VTE) incidence was 2.7% (95% CI: 1.1 - 4.3%) and discontinuation due to intolerance (DDI) rate was 14.9% (95% CI: 12.0 - 17.7%). Overall survival (OS), progression-free survival (PFS) and PN incidence were not pooled due to lack of reporting and trial heterogeneity. Prognostic factors identified included B2M (PFS) and advanced age (PFS and OS). Overall, thalidomide demonstrated an ORR approaching 30%, with low CR rate of 1.6% and VTE and DDI incidences of 3% and 15%, respectively.

Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.

Comparing antiemetic efficacy of different 5-HT(3)-receptor antagonists (5-HT(3)RAs) is difficult due to inter-study variability. Therefore, a meta-analysis was performed to comparatively evaluate dolasetron, granisetron, ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting (CINV).

Daily chlorhexidine mouthwash is often recommended for preventing chemotherapy-induced oral mucositis. Povidone-iodine, NaCl 0.9%, water salt soda solution and chamomile mouthwash are also recommended. However, the effectiveness of these mouthwashes is unclear. Therefore, we performed a systematic review to assess the effectiveness of mouthwashes in preventing and ameliorating chemotherapy-induced oral mucositis. Based on study quality, three out of five randomized controlled trials were included in a meta-analysis. The results failed to detect any beneficial effects of chlorhexidine as compared with sterile water, or NaCl 0.9%. Patients complained about negative side-effects of chlorhexidine, including teeth discoloration and alteration of taste in two of the five studies on chlorhexidine. The severity of oral mucositis was shown to be reduced by 30% using a povidone-iodine mouthwash as compared with sterile water in a single randomized controlled trial. These results do not support the use of chlorhexidine mouthwash to prevent oral mucositis.

Cytotoxic chemotherapy has a limited place in the management of advanced or recurrent endometrial cancer. Commonly used agents include cisplatin and doxorubicin, but the side-effect profile may be unacceptable for many patients. The feasibility of administration of combination chemotherapy is limited in many patients on account of significant co-morbidity. While early-stage endometrial adenocarcinoma is a common gynaecological cancer with a favourable prognosis, advanced or recurrent disease presents a difficult management problem. The platinum and anthracycline compounds have been widely used for many years, but their impact on progression-free survival (PFS) and overall survival (OS) is not clear. This systematic review aimed to evaluate both the benefits and adverse effects of cytotoxic chemotherapy in these women.

To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta-analysis.

To assess the effect of quinolone prophylaxis following chemotherapy for malignancies on the emergence of resistant bacteria in neutropenic patients.

The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline dosage schedules (i.e. peak doses and infusion durations) have been studied.