Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor approved for advanced renal cell carcinoma and imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumor. Following administration, sunitinib is metabolized by cytochrome P450 3A4 to an active metabolite (SU12662). The objective of this analysis was to assess sunitinib and SU12662 pharmacokinetics and to identify covariates that might explain variability in exposure following oral administration.

The primary objective of the analysis was to compare duration of survival in patients who received bevacizumab plus 5FU/LV, irinotecan or oxaliplatin based chemotherapy with the survival rate in a combined control groups of patients who received the same protocols alone, without bevacizumab.

Anthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non-randomized studies suggest that cardiotoxicity may be a problem. Individual patient data from trials in childhood ALL that randomized anthracyclines or methods of reducing cardiotoxicity were analysed by standard meta-analysis methods. Results were grouped and combined according to: addition of an anthracycline to standard therapy, type of anthracycline, mode of administration, and the use of a cardioprotectant. Data from 958 patients in 4 trials, recruiting between 1972 and 1984, showed that addition of an anthracycline reduced bone marrow relapse and, non-significantly, non-bone marrow relapse, resulting in an increased relapse-free interval. However there was a non-significant increase in induction failures, and in deaths in first remission. Event-free survival at 5 years was 56.7% with anthracycline versus 52.8% without (Odds Ratio = 0.91; 95% Confidence Interval = 0.76-1.10; P = 0.3). There were no significant differences found in other treatment comparisons. The limited data from trials did not demonstrate differences in clinically evident cardiotoxicity. Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL. The evidence on type of anthracycline, method of administration or use of cardioprotectant was insufficient to be able to rule out important differences.

Hand-foot skin reaction (HFSR) is an emerging issue in cancer treatment with multitargeted tyrosine kinase inhibitors (TKIs), leading to morbidity, suboptimal dosing, and poor compliance. The overall risk of HFSR is not clear for sunitinib, a TKI effective for metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor. We therefore conducted a systematic review and a meta-analysis to determine the risk of developing HFSR with sunitinib. Databases from PubMed and Web of Science for articles from July 1966 until July 2007 and abstracts presented at the American Society of Clinical Oncology conferences were searched to identify relevant studies. Eligible studies were prospective clinical trials that had described events of HFSR for patients who received singleagent sunitinib. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model. A total of 5005 patients with RCC and other cancers from 10 clinical trials were included for analysis. Among patients receiving sunitinib, the summary incidences of all-grade and high-grade HFSR were 18.9% (95% CI, 14.1%-24.8%) and 5.5% (95% CI, 3.9%-7.9%), respectively. Interestingly, patients with RCC have significantly decreased risk of HFSR compared with patients with non-RCC malignancy (RR, 0.56; 95% CI, 0.50-0.64; P < .001). In addition, sunitinib was associated with a significantly increased risk of all-grade HFSR (RR, 9.86; 95% CI, 3.1-31.31; P < .001) in comparison with controls. There is a significant risk of developing HFSR in patients with cancer receiving sunitinib. Adequate monitoring and intervention are recommended for reducing the toxicity.

Multiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups.

Follicular lymphoma is characterized by slow growth and an initially high rate of response to treatment, but patients typically relapse and experience progressive disease. Rituximab in combination with chemotherapy has been shown to improve overall survival in patients with follicular lymphoma compared with chemotherapy alone, but data from randomized clinical trials evaluating rituximab maintenance treatment in these patients are limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the overall survival of patients with follicular lymphoma.

Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more pronounced among STEMI patients. The aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of Sirolimus-Eluting Stent (SES) as compared to BMS in patients undergoing primary angioplasty for STEMI.

We aimed to assess the incidence of febrile neutropenia in patients with non small cell lung cancer treated with docetaxel as second line chemotherapy by systematic review and meta-analysis of clinical studies. Published studies were retrieved and included if they considered docetaxel at the licensed dose after a previous chemotherapy regimen, and reported the proportion of patients getting FN. Meta-analysis was conducted to estimate the proportion of patients who experience one or more episodes of FN. The pooled, random effects meta-analysis estimate for the proportion of patients who experience one or more episodes of FN on docetaxel was 5.95% (95% CI 4.22-8.31) based on 13 studies, comprising 1609 patients. No significant differences were seen either between studies that permitted the use of prophylactic granulocyte colony-stimulating factors or between phase II and phase III trials.Evidence from randomised controlled trials suggests that the incidence of FN with docetaxel is around 6% and therefore an important factor to consider in the choice of the chemotherapy regimen.

It is unclear if differential chemotherapy effects exist on overall survival (OS), response rate (RR) and toxicity depending on primary tumour origin [oesophageal versus oesophago-gastric junction (OGJ) versus gastric adenocarcinoma].

Gestational trophoblastic neoplasia (GTN) is a rare but curable disease. The incidence in Europe and North America is nearly 1.5 per 1000 live births but much higher rates are reported from Africa and Asia. The majority of the patients respond to evacuation of the uterus plus or minus chemotherapy, however, occasional patients will die. Patients are categorised into low or high risk groups using a variety of scoring systems. A large number of regimens are used worldwide in the management of low risk GTN; there are reports of 14 different regimens in the English literature. The choice of the regimen is usually dependent on geographic location, prior training and current experience with the specific regimen. Regimens have significant differences in the route of administration, hospitalisation and side effects and so have a bearing on healthcare cost. Patients are therefore exposed to different regimens with the potential for different response rates and different side effect profiles.

One of the most important adverse effects of anthracyclines is cardiotoxicity. A well-informed decision on the use of anthracyclines in the treatment of different types of childhood cancer should be based on the available evidence on both antitumour efficacy and cardiotoxicity.

Currently, no standard treatment is available for elderly patients with de novo/secondary acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy. New, less aggressive therapies are therefore needed. Histone deacetylase inhibitors (HDACi) are known to reduce proliferation and induce differentiation in hematological malignancies. With all-trans retinoic acid (ATRA) these effects have been reported to be even enhanced. Valproic acid (VPA) is an HDACi and has been known as anti-epileptic agent for many years. We treated 21 patients with de novo/secondary AML and 1 patient with myelodysplastic syndrome with ATRA (45 mg/m(2)/day in 2 doses, 14 days, q29 days) and VPA (150 mg/day 1 week, then 300 mg/day, continuously). Treatment was tolerated well with moderate side effects. 4 patients revealed hematological improvement and another 4 patients experienced a reduction in transfusion dependency. The overall response rate was 27%. Our study is presented together with an overview of the literature on the topic.

Basal cell carcinoma (BCC) is regarded as the most prevalent malignant skin tumor in whites. A variety of surgical and nonsurgical interventions are available to treat BCC. In recent years, an immune response modifier drug, imiquimod, has been approved in treating superficial BCC (sBCC). The objective of the authors was to review the published literature to evaluate outcomes such as efficacy, safety, and quality of life associated with imiquimod treatment among patients with sBCC. A MEDLINE search of the literature was performed to identify studies published between January 1, 1995 and March 31, 2008 that evaluated imiquimod efficacy, safety, and quality of life in treating BCC. Overall, imiquimod 5% cream was associated with increased clinical and histologic clearance among patients with sBCC as compared to placebo. The findings from short-term cost effectiveness studies suggest that use of imiquimod 5% cream can be more cost-effective than surgical interventions such as excision surgery among patients with superficial BCC. Future studies evaluating long term cost effectiveness of imiquimod treatment are warranted.

Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.

Venous thromboembolism is one of the leading causes of morbidity and mortality in patients with cancer. Concerns have arisen regarding the risk of venous thromboembolism with the novel antiangiogenic agent bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in venous thromboembolism is controversial.

To characterize the population pharmacokinetics of plitidepsin (Aplidin) in cancer patients.

Granulopoiesis-stimulating factors, such as granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF), are being used to prevent febrile neutropenia and infection in patients undergoing treatment for malignant lymphoma. The question of whether G-CSF and GM-CSF improve dose intensity, tumour response, and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive, a systematic review was undertaken.

Encephalopathy occurs in 10-40% of patients treated with high-dose ifosfamide. Proposed risk factors for encephalopathy include hepatic or renal dysfunction, brain metastases, electrolyte imbalances and drug-drug interactions.

Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis.