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.

The use of anthracyclines is limited by a dose-dependent cardiotoxicity (A-CT). The aim of this study was to gain insight in the currently available guidelines for monitoring cardiotoxicity during anthracycline therapy in children and in the monitoring recommendations currently used in European paediatric oncology trials. An extensive literature search to identify guidelines was performed and one guideline was identified. Twelve protocols including anthracycline therapy were evaluated. With regard to the minimally required diagnostic tests, parameters and definitions of A-CT most protocols roughly followed the guideline. However, both monitoring schedules and recommendations to prevent further cardiac damage in case A-CT was diagnosed varied widely between protocols and only a minority of the protocols followed the recommendations of the guideline. In conclusion, despite an existing guideline, there is a wide variation in the recommendations for monitoring cardiac function during anthracycline therapy in the currently used European paediatric oncology protocols. A possible explanation could be the lack of rigorous evidence on the most optimal way to monitor cardiac function in children treated with anthracyclines. There is a strong need for evidence from clinical research which can support recommendations for monitoring cardiac function during anthracycline therapy for childhood cancer. In the meantime, it is important to standardize the used cardiac monitoring schedules.

Docetaxel has to be considered as the reference control arm for second line chemotherapy for advanced NSCLC. Weekly docetaxel has been compared to standard 3-weekly schedule in a randomized fashion to determine if such schedule improves survival and quality of life. We performed a literature-based meta-analysis of all randomized clinical trials (RCTs) comparing weekly over 3-weekly docetaxel in advanced NSCLC.

The aim of these meta-analyses was to evaluate the effectiveness of interventions for the prevention of oral mucositis in cancer patients treated with head and neck radiotherapy and/or chemotherapy, with a focus on randomized clinical trials. A literature search was performed for reports of randomized controlled clinical studies, published between 1966 and 2004, the aim of which was the prevention of mucositis in cancer patients undergoing head and neck radiation, chemotherapy, or chemoradiation. The control group consisted of a placebo, no intervention, or another intervention group. Mucositis was scored by either the WHO, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) score, or the absence or presence of ulcerations, or the presence or absence of grades 3 and 4 mucositis. The meta-analyses included 45 studies fulfilling the inclusion criteria, in which 8 different interventions were evaluated: i.e., local application of chlorhexidine; iseganan; PTA (polymyxin E, tobramycine, and amphotericin B); granulocyte macrophage-colony-stimulating factor/granulocyte colony-stimulating factor (GM-CSF/G-CSF); oral cooling; sucralfate and glutamine; and systemic administration of amifostine and GM-CSF/G-CSF. Four interventions showed a significant preventive effect on the development or severity of oral mucositis: PTA with an odds ratio (OR) = 0.61 (95% confidence interval [CI], 0.39-0.96); GM-CSF, OR = 0.53 (CI: 0.33-0.87); oral cooling, OR = 0.3 (CI: 0.16-0.56); and amifostine, OR = 0.37 (CI: 0.15-0.89). To date, no single intervention completely prevents oral mucositis, so combined preventive therapy strategies seem to be required to ensure more successful outcomes.

Erythropoiesis-stimulating proteins (ESPs) are indicated for the treatment of chemotherapy-induced anemia (CIA). Evidence-based guidelines and systematic reviews of the management of CIA do not yet include all currently approved ESPs or all of the clinically relevant benefits and risks of ESPs.

To characterize the population pharmacokinetics of tipifarnib.

The risk of thrombosis in children with acute lymphoblastic leukemia (ALL) reportedly ranges between 1% and 37%. Epidemiologic studies have usually been hampered by small numbers, making accurate estimates of thrombosis risk in ALL patients very difficult. The aim of this study was to better estimate the frequency of this complication and to define how the disease, its treatment, and the host contribute to its occurrence. We made an attempt to combine and analyze all published data on the association between pediatric ALL and thrombosis, by using a meta-analytic method. The rate of thrombosis in 1752 children from 17 prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on several factors. Most of the events occurred during the induction phase of therapy. Lower doses of asparaginase (ASP) for long periods were associated with the highest incidence of thrombosis, as were anthracyclines and prednisone (instead of dexamethasone). The presence of central lines and of thrombophilic genetic abnormalities also appeared to be frequently associated with thrombosis. In conclusion, the overall thrombotic risk in ALL children was significant, and the subgroup analysis was able to identify high-risk individuals, a finding that will hopefully guide future prospective studies aimed at decreasing this risk.

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

The colony-stimulating factors (CSFs) are widely utilized to prevent neutropenic complications in both adults and children, but randomized controlled trials in the pediatric setting have reported varied results. A systematic review of the literature and meta-analysis were conducted to definitively assess the impact of prophylactic CSFs on the risk of febrile neutropenia (FN) in pediatric oncology patients.

There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms.

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).

Oral and gastrointestinal (GI) mucositis are frequent complications of chemotherapy and radiotherapy for cancer, contributing to not only the morbidity of treatment but its cost as well. The risk associated with specific chemotherapeutic agents, alone and in combination, has been characterized previously. In the current study, we sought to estimate the risk associated with newer regimens for the treatment of non-Hodgkin's lymphoma (NHL) and common solid tumors.

High intake of soy foods has been proposed to contribute to the low breast cancer risk in Asian countries. However, results of epidemiologic studies of this association are highly variable, and experimental data suggest that soy constituents can be estrogenic and potentially risk enhancing. Thus, rigorous evaluation of available epidemiologic data is necessary before appropriate recommendations can be made, especially for women at high risk of breast cancer or those who have survived the disease.

Benefit and harm associated with treating actinic keratosis (AK) with the immune response modifier imiquimod was assessed using published randomized-controlled trials. Five randomized double-blind trials lasted 12-16 weeks and treated 1,293 patients. Complete clearance occurred in 50% of patients treated with imiquimod, compared to 5% treated with vehicle, and the number needed to treat (NNT) for one patient to have their keratosis completely cleared after 12-16 weeks was 2.2 (95% confidence interval 2.0-2.5). For partial (>/=75%) clearance the NNT was 1.8 (1.7-2.0). The proportion of patients with any adverse event, any local adverse event, or any treatment-related adverse event was substantially higher with imiquimod than with vehicle, and numbers needed to harm for one additional adverse event with imiquimod over 12-16 weeks ranged from 3.2 to 5.9. Particular local adverse events with imiquimod included erythema (27%), scabbing or crusting (21%), flaking (9%), erosion (6%), edema (4%), and weeping (3%). Imiquimod 5% cream was effective in the treatment of AK, preventing potential development of squamous cell carcinoma. Future investigation might be aimed at elucidating optimal dosing to minimize adverse events without detriment to efficacy, and evaluating long-term recurrence.

Despite several randomised trials comparing radiotherapy alone with concomitant radio-chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC), it is not clear whether the addition of chemotherapy improves survival.

A systematic review and meta-analysis was conducted to test the hypothesis that oncology health care workers are at an increased risk of cancer, reproductive complications and acute toxic events.

Nonsurgical fertility-preserving treatment of well-differentiated endometrial cancer with systemic progestins has been described for young women who desire to preserve their fertility. The overall response to progestin treatment in 9 retrospective studies is 79% with 79 subsequent live births. Recurrence can be expected in approximately 36-40% of conservatively treated patients who initially responded. Synchronous ovarian cancer has been reported in approximately 9%. However, amongst 162 receiving systemic, continuous treatment with progestins no death caused by cancer has been reported. We review guidelines for diagnosis, treatment and follow-up in young women undergoing conservative treatment for endometrial cancer.

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

In this analysis of the safety and efficacy of BAY 43-9006 (sorafenib) -- a novel, oral multi-kinase inhibitor with effects on tumour and its vasculature -- pooled data were obtained from four phase I dose-escalation trials. Time to progression (TTP) was compared in patients with/without grade 2 skin toxicity/diarrhoea. Grade 3 hand-foot skin reactions (HFS; 8%) and diarrhoea (6%) were common. At the recommended 400mg bid dose for phase II/III trials (RDP), 15% of patients experienced grade 2/3 HFS, and 24% experienced grade 2/3 diarrhoea. Sorafenib induced stable disease for 6 months in 12% of patients (6% stabilized for 1 year). Patients receiving sorafenib doses at or close to the RDP, who experienced skin toxicity/diarrhoea, had a significantly increased TTP compared with patients without such toxicity (P < 0.05). Sorafenib was well tolerated at the RDP, and induced sustained disease stabilization, particularly in patients with skin toxicity/diarrhoea.

Multiple myeloma accounts for 10% of all haematologic malignancies worldwide. In Europe, over 10,000 new cases and nearly 8000 deaths were attributed to multiple myeloma in 2000. Unlike other malignancies, in which surgery and radiation are important treatment modalities, myeloma is exclusively treated with stem cell transplantation and drug therapy, requiring pharmacists to stay abreast of new developments. The melphalan-prednisolone and vincristine-doxorubicin-dexamethasone (VAD) regimens, which have been standard treatments for multiple myeloma over the past few decades, have yielded responses without real survival benefits. Transplantation utilizing high-dose chemotherapy has produced the only meaningful survival benefits for patients with multiple myeloma, but many patients are not candidates for this aggressive treatment option. More effective therapies for multiple myeloma are needed.