In 1997, the anti-CD20 monoclonal antibody (MAb) rituximab became the first MAb approved for clinical use in oncology, and ushered in a new era of rationally designed targeted agents in cancer therapeutics. It is currently approved for use in non-Hodgkin lymphoma (NHL), chronic lymphoid leukemia (CLL), and rheumatoid arthritis (RA). Rituximab is non-mutagenic, associated with low treatment-related toxicity, and few, if any, long term adverse events, making it an attractive agent to be tried in off-label settings like Hodgkin lymphoma (HL). HL consists of two distinct subtypes - classic HL (cHL) and lymphocyte predominant HL (LPHL). CD20 is present in virtually all patients with LPHL, and in a significant minority of patients with cHL. In this CD20 positive sub-population, the use of rituximab is a rational intervention strategy. Rituximab has been used in patients with cHL as well as LPHL with good efficacy. In this article, we provide a clinically-oriented overview of the use of rituximab in the different sub-types of HL, and report updated results of our series of 8 LPHL patients treated with rituximab. A systematic review of the literature is also presented.

To systematically review randomized, controlled clinical trials for managing osteoporosis, cancer treatment-induced bone loss, and bone metastases from breast cancer using zoledronic acid (ZOL).

This systematic review explores studies using biomechanical analysis of hyoid bone displacement in videofluoroscopy of swallowing as a spatial outcome parameter to evaluate intervention effects. Two authors independently carried out the literature search using the electronic databases Embase, PubMed, and Cochrane Library. Differences in their search findings were settled by discussion. The search was limited to publications in the English, German, French, Spanish, or Dutch language. MeSH terms were used, supplemented by free-text words to identify the most recent publications. In addition, reference lists were searched by hand. Only studies using videofluoroscopy to evaluate the biomechanical effects of swallowing interventions in dysphagic subjects were included in the review. While the body of literature on measuring hyoid bone displacement in videofluoroscopy has grown, only 12 studies met the inclusion criteria. Several of the 12 studies had methodological shortcomings. In general, the conclusions could not be compared across the studies because of their heterogeneous designs and outcome measures. Overall, several intervention effect studies reported significant results. In particular, bolus modification and swallowing maneuvers showed a greater range of hyoid bone displacement. In light of this review, further research on hyoid bone displacement as a spatial variable in well-defined patient populations using well-defined videofluoroscopic protocols to measure intervention effects is recommended.

Preclinical models and data from clinical trials suggest that cancer is a preventable disease. However, demonstration of a preventive effect requires large phase III clinical trials of long duration and involves many thousands of participants. The decision to proceed with phase III studies therefore must be informed by robust efficacy and safety data. This requires a systematic review of all available preclinical, epidemiological, and clinical data, along with a mechanistic understanding of the biology of the disease under study. In this review we identify the issues that are critical to decision-making prior to embarking on late phase prevention clinical trials and provide a framework for making such decisions.

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).

Bevacizumab, an anti vascular endothelial growth factor antibody is licensed in several tumours and widely used in colorectal cancer. However, bevacizumab has several adverse effects which may appear unexpectedly and differ according to the tumour.

To determine whether gonadotropin-releasing hormone (GnRH) analog cotreatment with chemotherapy provides better reproductive outcomes for women at risk of premature ovarian failure (POF) as a side-effect of gonadotoxic chemotherapy.

Among glucocorticoids, dexamethasone is most widely used for treatment of cerebral edema because of its long biological half-life and its low mineralocorticoid activity (sodium retaining).

Dose-dense chemotherapy has become a mainstay regimen in the adjuvant setting for women with high-risk breast cancer. We performed a systematic review and meta-analysis of the existing data from randomized controlled trials regarding the efficacy and toxicity of the dose-dense chemotherapy approach in nonmetastatic breast cancer.

The role of the widely-used angiogenesis inhibitor bevacizumab in the development of serious hemorrhage is not well defined in cancer patients. This study was conducted to determine the overall risk of hemorrhage with bevacizumab by a systematic review and meta-analysis of randomized controlled trials (RCT).

The initial appearance of subacute cutaneous lupus erythematosus (SCLE) skin lesions in conjunction with Ro/SS-A autoantibodies occurring as an adverse reaction to hydrochlorothiazide [i.e. drug-induced SCLE (DI-SCLE)] was first reported in 1985. Over the past decade an increasing number of drugs in different classes has been implicated as triggers for DI-SCLE. The management of DI-SCLE can be especially challenging in patients taking multiple medications capable of triggering DI-SCLE. Our objectives were to review the published English language literature on DI-SCLE and use the resulting summary data pool to address questions surrounding drug-induced SCLE and to develop guidelines that might be of value to clinicians in the diagnosis and management of DI-SCLE. A systematic review of the Medline/PubMed-cited literature on DI-SCLE up to August 2009 was performed. Our data collection and analysis strategies were prospectively designed to answer a series of questions related to the clinical, prognostic and pathogenetic significance of DI-SCLE. One hundred and seventeen cases of DI-SCLE were identified and reviewed. White women made up the large majority of cases, and the mean overall age was 58·0 years. Triggering drugs fell into a number of different classes, highlighted by antihypertensives and antifungals. Time intervals ('incubation period') between drug exposure and appearance of DI-SCLE varied greatly and were drug class dependent. Most cases of DI-SCLE spontaneously resolved within weeks of drug withdrawal. Ro/SS-A autoantibodies were present in 80% of the cases in which such data were reported and most remained positive after resolution of SCLE skin disease activity. No significant differences in the clinical, histopathological or immunopathological features between DI-SCLE and idiopathic SCLE were detected. There is now adequate published experience to suggest that DI-SCLE does not differ clinically, histopathologically or immunologically from idiopathic SCLE. It should be recognized as a distinct clinical constellation differing clinically and immunologically from the classical form of drug-induced systemic lupus erythematosus.

• To estimate the benefits and harms of 5-α-reductase inhibitors (5-α-RIs) in preventing prostate cancer.

To conduct a systematic review in order to compare adverse effects (AE) and the reporting of harm in randomised controlled trials (RCTs) and non-RCTs evaluating intravitreal ranibizumab and bevacizumab in age-related macular degeneration.

We performed a systematic review and meta-analysis to determine the impact of neutropenia or leukopenia experienced during chemotherapy on survival.

Trastuzumab is used widely for the treatment of early and advanced breast cancer. However, concerns have arisen regarding its cardiac toxicity. We did a systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess the overall risk of cardiac dysfunction associated with trastuzumab treatment.

Rituximab is a chimeric monoclonal antibody against CD20 that is used mainly for the treatment of CD20-positive lymphoma. Recently, its use has been expanded to include treatment of other nonmalignant diseases such as rheumatologic diseases and autoimmune cytopenia. Correlating with the increased use of rituximab has been an increased number of reports of its late adverse effects. One of these is late-onset neutropenia (LON). Most investigators define LON as grade III-IV neutropenia occurring 3-4 weeks after the last treatment with rituximab, in the absence of an alternative explanation for the neutropenia.We report 6 cases of LON identified in our institution. Four patients were treated for diffuse large B-cell lymphoma, and 2 patients for follicular lymphoma. Median patient age was 68 years (range, 33-83 yr); LON appeared after a median interval of 77 days (range, 42-153 d) and lasted for a median of 5 days (range, 1-45 d). Five of the 6 patients presented with infectious complications, and 4 patients experienced recurrent episodes of neutropenia. One patient presented with LON and concomitant subacute pulmonary disease that was attributed to rituximab therapy.In addition to our own case series we present a systematic review of the literature, which we performed to compile data to describe better the syndrome of LON. Systematic studies, case series, and case reports were extracted. Most studies dealing with LON are retrospective by design and are limited by the heterogeneous populations included in the analysis. The incidence of LON is generally reported to be in the range of 3%-27%. Data regarding populations at risk are not consistent, and in some instances are conflicting.Patients considered at increased risk of LON include patients after autologous stem cell transplantation, patients treated for acquired immunodeficiency syndrome (AIDS)-related lymphoma, and patients treated with purine analogues. Patients who received previous cytotoxic treatment as well as those treated with more intensive chemotherapy or with chemotherapy in combination with radiotherapy are also considered to be at risk of LON. In addition, advanced stages of disease and having received multiple doses of rituximab are risk factors for LON.The mechanism of LON is poorly understood. Direct toxicity is very unlikely. Some speculate that there may be an infectious etiology involved, as well as an antibody-mediated process, but these ideas have not been substantiated. The concept of a lymphocyte subpopulation imbalance leading to LON has been presented based on the demonstration of T-LGL in peripheral blood and bone marrow of patients with LON. Perturbations in stromal-derived factor-1 and in the BAFF cytokine have also been discussed as potential players in the pathogenesis of LON. A recent study correlated specific polymorphism in the immunoglobulin G Fc receptor FCγRIIIa 158 V/F with increased rates of LON.The clinical significance of LON is important because it may affect treatment strategies. Of note, infectious complications are not very frequent and not very severe. Pooling data from the major retrospective studies reveals an infection rate of 16.9%. Most infections were mild and resolved promptly. One death occurred from infection during neutropenia. Repeated episodes of LON are not uncommon, but it is so far impossible to identify those patients at risk of these relapsing episodes of LON. Re-treatment with rituximab after LON may result in recurrent episodes, but the implications and risks are uncertain at the present time. The role of growth factors once LON appears is ill defined, and the decision to use them should be made on a case-by-case basis.

Nausea and vomiting are still a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting and associated clinical problems.

The nursing profession has been associated with several adverse pregnancy outcomes. However, the associations between occupational exposures and adverse pregnancy outcomes among this group have not been systematically examined. This review collates all epidemiological evidence to examine the strength of associations and consistency among eligible studies.

Today the occupational health and safety risk involved when handling most anticancer drugs is well recognized and, as a result of regulatory requirements, safety measures have been established. There is little knowledge about the occupational hazard posed by handling monoclonal antibodies assigned to ATC Class L01XC. The aim of our study was to evaluate the occupational risk of monoclonal antibodies. Using the information obtained in a systematic review of the literature, the potentially dangerous properties of the active drug substances were assessed using a specially devised algorithm. As a result, all monoclonal antibodies in question were categorized as substances with developmental toxicity. In addition, gemtuzumab ozogamicin was categorized as mutagenic. In view of the high molecular weights and the proteinogenic nature of monoclonal antibodies, the route of exposure for health care staff is limited to inhalation, unless there is an accident. Employers should implement the necessary administrative and engineering controls. Employees should adhere to the standards in order to avoid occupational exposure. The hazard assessment algorithm devised and the evaluation procedure may also be used for other drugs considered to be dangerous.

To compare intravitreal bevacizumab (IVB) injection versus macular photocoagulation (MPC) or a combination of intravitreal bevacizumab and intravitreal triamcinolone acetonide (IVB/IVTA) injection in improving visual acuity (VA) of patients with primary diabetic macular oedema (DMO).