Although several randomized trials have been performed comparing weekly docetaxel (wD) with standard docetaxel once every 3 weeks (3wD) as second-line treatment of advanced non-small-cell lung cancer (NSCLC), no single trial had sufficient power to detect clinically relevant differences in survival.

Randomized controlled trials (RCTs) reported conflicting results on the impact of high-dose chemotherapy (HDCT) and autologous stem cell transplantation in the first-line treatment of patients with aggressive non-Hodgkin lymphoma (NHL).

Recent years have seen tremendous progress in our understanding of the mechanisms of neovascular diseases of the eye. Antiangiogenic treatment options are now widely used in the management of age-related maculopathy (AMD) and diabetic retinopathy. The aim of this article is to highlight some novel methods of local antiangiogenic treatment of the cornea and conjunctiva and in the anterior chamber of the eye.

Bevacizumab is the first U.S. Food and Drug Association-approved vascular endothelial growth factor-targeted agent that greatly increases progression-free and overall survival in combination with standard chemotherapy regimens in patients with metastatic colorectal cancer. Although bevacizumab is generally well tolerated, some serious adverse events have occurred in some patients in clinical trials, including arterial thromboembolism and gastrointestinal (GI) perforation. GI perforation was first observed in the pivotal phase 3 trial, in which six events occurred in bevacizumab group (1.5%), compared with no events in the control group. Since then, similar rates of GI perforation have been observed in other large trials. Typical presentation was abdominal pain associated with constipation and vomiting. Such events occurred throughout treatment and were not correlated with duration of exposure. No difference in rate of GI perforations was found in patients who did and did not have a baseline history of peptic ulcer disease, diverticulosis, and history of chronic use of nonsteroidal anti-inflammatory drugs. However, the incidence of GI perforation seemed to be higher in patients with primary tumor intact, recent history of sigmoidoscopy or colonoscopy, or previous adjuvant radiotherapy, but it is necessary to confirm these preliminary findings by multivariate analyses. The mechanism responsible for causing GI perforation is not known and may be multifactorial. Bevacizumab should be permanently discontinued in patients who develop GI perforation. This article reviews the incidence, presentation, pathogenesis, risk factors, and management of GI perforation in patients with colorectal cancer who are treated with bevacizumab.

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.

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been suggested as a treatment option for patients with colorectal peritoneal carcinomatosis. However, the survival benefit is achieved at the expense of moderate to high perioperative morbidity and mortality.

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).

Epidemiologic findings are inconsistent concerning risk for breast cancer associated with low folate intake or blood folate levels. We performed a meta-analysis of prospective and case-control studies to examine folate intake and levels in relation to risk of breast cancer.

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.

A number of collaborative trial groups developed prospective randomized trials to compare autologous stem cell transplantation (ASCT) with non-transplant therapy (interferon-alpha alone or in combination) for chronic myeloid leukaemia (CML) with the aim of obtaining reliable evidence on the possible benefit of ASCT. With the arrival of tyrosine kinase inhibitors, notably imatinib, these trials closed early without reaching their recruitment targets and no trial was able to address its objectives. Following discussions with the principal investigators, it was agreed that a meta-analysis be performed to attempt to determine the effect of ASCT on the main outcomes.

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.

A large number of trials have assessed various chemotherapy regimens for the treatment of advanced cervical cancer, but there is uncertainty about the magnitude of survival benefits.

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

Numerous randomized trials have compared different chemotherapy regimens in women with ovarian cancer. Although ovarian cancer survival has improved in recent years, the magnitude of these incremental benefits across diverse regimens is unclear.

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.

The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied.