Androgen deprivation therapy (ADT), which is used in the treatment of prostate cancer (PCa), is associated with increased morbidity. Severe bone loss is a major consequence of androgen ablation and with an increasing number of patients undergoing this treatment, the incidence of osteoporosis and fractures can be expected to increase with a significant impact on healthcare. To evaluate the prevalence of osteoporosis, we conducted a review of the literature on bone health in men with PCa undergoing ADT. A meta-analysis was conducted using the quality effects model, and sources of heterogeneity were further explored by consideration of discordant effect sizes of included studies in the meta-analysis and examining reasons thereof. Our analyses indicate that the prevalence of osteoporosis varies between 9 and 53 % with this variation partially explained by treatment duration, disease stage, ethnicity and site of osteoporosis measurement. While it is well known that a rapid decline in bone health amongst men with PCa on ADT occurs, this meta-analysis documents the high prevalence of osteoporosis in this population and reinforces the need of preventative approaches as part of usual care of PCa patients.

Temozolomide (TMZ) has received much attention, notably in the treatment of malignant glioma and malignant melanoma. The objective of this study was to compare the clinical efficacy and safety of TMZ alone and TMZ-based combination drug therapy in patients with melanoma. Using "temozolomide" as a keyword combined with "melanoma" and "randomized controlled trials" as Medical Subject Headings, the following electronic databases were searched: the Cochrane library, MEDLINE, EBSCO, EMBASE, Ovid, cNKI, and cBMDisc. The evaluating indicators were overall response rate (ORR), 1-year survival rate, and several of the most frequent adverse events. Five randomized controlled trials met our criteria and were included in the meta-analysis, with a total of 703 participants (309 patients received TMZ alone, and 394 patients received combined regimens). The meta-analysis showed that the ORR for TMZ-based drug therapy was higher than TMZ alone [relative risk (RR) = 1.44; 95% confidence interval (CI), 1.06-1.95], but the 1-year survival rate was not significantly different between the two groups (RR = 1.13; 95% CI, 0.92-1.40). These results suggested that the impact of these increased response rates was not translated into a survival benefit. Moreover, we found no difference in the incidence of adverse events analyzed. The currently available evidence showed that the TMZ-combination therapy may moderately improve the response rate, but there was no corresponding increased toxicity. Future large-scale, high-quality, placebo-controlled, double-blind trials are needed.

Regorafenib is a novel multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). Hypertension is one of the major adverse events of this agent, but to date the incidence and risk of hypertension with regorafenib have not been systematically investigated. We have conducted a systematic review and meta-analysis of published clinical trials to determine its overall incidence and risk.

No randomized trials have directly compared dasatinib with nilotinib for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase. The objective of this study was to indirectly compare these therapies using evidence from randomized trials versus imatinib, the current standard of care.

Several studies have demonstrated that sorafenib is effective in the treatment of unresectable hepatocellular carcinoma (HCC). We performed a systematic review of the efficacy and safety of sorafenib in Child-Pugh A patients with unresectable HCC. The value of sorafenib treatment in different subgroups was examined.

UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. However, knowledge about the effects of these polymorphisms is rarely used for the individualization of drug therapy. Here, we present a quantitative systematic review of clinical studies on the impact of UGT variants on drug metabolism to clarify the potential for genotype-adjusted therapy recommendations. Data on UGT polymorphisms and dose-related pharmacokinetic parameters in man were retrieved by a systematic search in public databases. Mean estimates of pharmacokinetic parameters were extracted for each group of carriers of UGT variants to assess their effect size. Pooled estimates and relative confidence bounds were computed with a random-effects meta-analytic approach whenever multiple studies on the same variant, ethnic group, and substrate were available. Information was retrieved on 30 polymorphic metabolic pathways involving 10 UGT enzymes. For irinotecan and mycophenolic acid a wealth of data was available for assessing the impact of genetic polymorphisms on pharmacokinetics under different dosages, between ethnicities, under comedication, and under toxicity. Evidence for effects of potential clinical relevance exists for 19 drugs, but the data are not sufficient to assess effect size with the precision required to issue dose recommendations. In conclusion, compared to other drug metabolizing enzymes much less systematic research has been conducted on the polymorphisms of UGT enzymes. However, there is evidence of the existence of large monogenetic functional polymorphisms affecting pharmacokinetics and suggesting a potential use of UGT polymorphisms for the individualization of drug therapy.

The management of individual patients requiring anthracyclines remains challenging because uncertainty persists on predictors of cardiotoxicity. We aimed to perform a systematic review and meta-analysis on incidence and predictors of anthracycline chemotherapy in patients with cancer. Databases were searched for pertinent studies. Meta-analytic pooling with random-effects methods was performed for incidence estimates, while relying on descriptive statistics for prevalence and strength of association of predictors. From 16,054 retrieved citations, 18 studies reporting on 49,017 patients with cancer were included, with 22,815 treated with anthracyclines. After a median follow-up of 9 years, clinically overt cardiotoxicity occurred in 6% (95% confidence interval 3% to 9%), whereas subclinical cardiotoxicity developed in 18% (95% confidence interval 12% to 24%). Appraisal of independent risk factors of cardiotoxicity showed that cumulative anthracycline dose was most consistently reported as an accurate and robust predictor of cardiotoxicity, with an acceptable prognostic role also for chest radiotherapy, African-American ethnicity, very young or very old age, diabetes, hypertension, very high or very low body weight, or severe co-morbidities. In conclusion, despite ongoing refinements in chemotherapy regimens, anthracyclines still pose a significant risk of cardiotoxicity, especially in those requiring a high cumulative dose or chest radiotherapy.

The Oxford Overview process has provided us with extremely high-powered meta-analyses assessing the role of adjuvant chemotherapy in early breast cancer. From the most recent publication, the proportional benefits from chemotherapy are relatively equivalent across all patient subgroups, a finding contradictory to our growing understanding of the role of tumour biology in dictating chemosensitivity. Several factors, including heterogeneity of patient groups and chemotherapy regimens, lack of data on underlying tumour biological subtypes, and confounding effect of chemotherapy-induced ovarian suppression in premenopausal women with hormone receptor positive breast cancer, impact on the applicability and clinical utility of the Overview in current and future oncological practice. With these considerations, the Overview has become less clinically relevant as a tool for guiding adjuvant chemotherapy treatment decisions, and a new direction is required.

To explore the combination therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) on acute promyelocytic leukemia (APL).

Various antiemetic agents are commonly administered during and after chemotherapy to prevent nausea and vomiting depending on the emetogenic risk. Data specific for patients older than 65 are rarely discussed and it is often assumed that such patients have less risk of nausea and vomiting and might not need the same prevention.

Observational and preclinical studies suggested an association between the expression of thymidylate synthase (TS) and clinical effects of pemetrexed-based chemotherapy in non-small-cell lung cancer (NSCLC) patients. However, the predictive value of TS for pemetrexed-containing chemotherapy regimen remained controversial. The aim of the study was to further appraise the association between the expression of TS and clinical efficacy pemetrexed-based chemotherapy in NSCLC patients.

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.

There are many phase I trials of oncology drug combinations, very few of which report clinically significant pharmacokinetic interactions. We hypothesized that the utility of such pharmacokinetic drug-drug interaction (DDI) studies is low in the absence of a mechanistic hypothesis.

Patients with metastatic renal cell carcinoma (mRCC) and a good performance status typically receive an anti-vascular endothelial growth factor receptor (VEGFR) TKI (sunitinib or pazopanib) as initial therapy. Upon disease progression or intolerance, there are four orally administered agents approved in the second-line setting (including cytokine-refractory). However, head-to-head comparative trial data are limited. In this study, an indirect statistical comparison of safety and efficacy was undertaken between axitinib, sorafenib, pazopanib and everolimus in second-line therapy mRCC.

Mammalian target of rapamycin (mTOR) inhibitors, temsirolimus and everolimus, are currently approved for the treatment of several malignancies. Hematological toxicities have been reported with these drugs, but overall incidence and relative risk remains undefined. We perform an up-to-date meta-analysis to determine the incidence and risk of hematologic toxicities associated with mTOR inhibitors.

The objective of this meta-analysis in patients with myeloma was to test the hypothesis that the addition of bortezomib to induction therapy not only improves the depth of response but also improves post-transplant progression-free survival (PFS) and overall survival (OS) outcomes.

Abstract We conducted a systematic review of grade 3/4 adverse events (AEs) reported in prospective trials enrolling patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) receiving maintenance rituximab (MR). Random-effects models were used to calculate summary estimates and 95% confidence intervals for the proportion of AEs occurring during MR. Differences by induction program, histology, setting and MR schedule were examined by stratified analyses and univariate random-effects meta-regression. Eleven trials met the search criteria, with nine sufficiently reporting AEs during the MR phase. Of 1009 patients receiving MR, the proportion experiencing cumulative grade 3/4 toxicity was 24% (95% confidence interval [CI]: 14-36%). Patients receiving MR every 6 months as four weekly infusions for 2 years had significantly less toxicity compared with those receiving MR every 2 months (10% vs. 28%; p = 0.035). Patients treated with rituximab alone during induction had fewer toxicities compared to those treated with rituximab plus chemotherapy induction (12% vs. 35%; p = 0.031). Myelosuppression and infections were the most common toxicities. Our literature analysis suggests that MR given every 6 months and rituximab alone as induction may be associated with fewer grade 3/4 AEs for patients with FL and MCL; however, assessing the true independent impact of induction regimens and schedule on toxicity will require prospective trials.

The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving tyrosine kinase inhibitors (TKIs) through a large up-to-date meta-analysis of available clinical trials.

To compare the efficacy and safety between anthracycline & taxane and anthracycline in the treatment of breast cancer.

The incidence rates of colorectal cancer (CRC) are increasing in a number of different regions, and recent studies have indicated that addition of bevacizumab to CRC therapy is beneficial. To better understand the relative risk (RR) of adverse events associated with use of bevacizumab, we systematically reviewed published clinical trials that studied use of bevacizumab in treatment of patients affected by metastatic CRC (mCRC).