Second (2nd)-generation tyrosine kinase inhibitors (TKI) (dasatinib, nilotinib) are effective in patients with all phases of chronic myeloid leukaemia (CML). Dose reductions and treatment interruptions are frequently required due to toxicity, but their significance is unknown. We analysed the impact of dose reductions/interruptions and dose intensity of 2nd-generation TKI on response and survival. A total of 280 patients with CML (all phases) were analysed. Dose reductions were considered when the daily dose was below the standard dose. Dose intensity was determined based on the percentage of the ideal dose intensity. Overall, 176 patients (63%) required treatment interruptions and/or dose reduction at least once during therapy. Dose reductions/interruptions, analysed as a time-dependent covariate, were associated with worse failure-free survival only in patients with untreated CML. Dose intensity analysis did not reveal a worse response or survival in patients who received a lower dose intensity (<100%) during therapy or during the first 6 months. In conclusion, dose reductions and treatment interruptions of 2nd generation TKI in patients with CML have a minimal impact in the response rate and survival of these patients. Further studies are required to determine whether there might be a minimum adequate dose of these agents.

Treatment with the chemotherapeutic agent bevacizumab, a humanized mAb that neutralizes vascular endothelial growth factor, can lead to proteinuria and renal damage. The risk factors and clinical outcomes of renal adverse events are not well understood. We performed a systematic review and meta-analysis of published randomized, controlled trials to assess the overall risk for severe proteinuria with bevacizumab. We analyzed data from 16 studies comprising 12,268 patients with a variety of tumors. The incidence of high-grade (grade 3 or 4) proteinuria with bevacizumab was 2.2% (95% confidence interval [CI] 1.2 to 4.3%). Compared with chemotherapy alone, bevacizumab combined with chemotherapy significantly increased the risk for high-grade proteinuria (relative risk 4.79; 95% CI 2.71 to 8.46) and nephrotic syndrome (relative risk 7.78; 95% CI 1.80 to 33.62); higher dosages of bevacizumab associated with increased risk for proteinuria. Regarding tumor type, renal cell carcinoma associated with the highest risk (cumulative incidence 10.2%). We did not detect a significant difference between platinum- and non-platinum-based concurrent chemotherapy with regard to risk for high-grade proteinuria (P = 0.39). In conclusion, the addition of bevacizumab to chemotherapy significantly increases the risk for high-grade proteinuria and nephrotic syndrome.

The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT₃ receptor antagonists to assess its translational validity.

The objective of this work is to perform a systematic review and meta-analysis of all randomized controlled trials comparing a single intravenous dose of palonosetron (PAL) 0.25 mg with other 5-HT(3)R in patients receiving moderately or highly emetogenic (MoHE) chemotherapy.

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

To evaluate the efficacy and safety in treatment of ocular neovascularization by Bevacizumab versus Ranibizumab.

Preclinical cellular response profiling of tumor models has become a cornerstone in the development of novel cancer therapeutics. As efforts to predict clinical efficacy using cohorts of in vitro tumor models have been successful, expansive panels of tumor-derived cell lines can recapitulate an "all comers" efficacy trial, thereby identifying which tumors are most likely to benefit from treatment. The response profile of a therapy is most often studied in isolation; however, drug treatment effect patterns in tumor models across a diverse panel of compounds can help determine the value of unique molecular target classes in specific tumor cohorts. To this end, a panel of 19 compounds was evaluated against a diverse group of cancer cell lines (n = 311). The primary oncogenic targets were a key determinant of concentration-dependent proliferation response, as a total of five of six, four of four, and five of five phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, insulin-like growth factor-I receptor (IGF-IR), and mitotic inhibitors, respectively, clustered with others of that common target class. In addition, molecular target class was correlated with increased responsiveness in certain histologies. A cohort of PI3K/AKT/mTOR inhibitors was more efficacious in breast cancers compared with other tumor types, whereas IGF-IR inhibitors more selectively inhibited growth in colon cancer lines. Finally, specific phenotypes play an important role in cellular response profiles. For example, luminal breast cancer cells (nine of nine; 100%) segregated from basal cells (six of seven; 86%). The convergence of a common cellular response profile for different molecules targeting the same oncogenic pathway substantiates a rational clinical path for patient populations most likely to benefit from treatment. Cancer Res; 70(9); 3677-86. (c)2010 AACR.

Post-chemotherapy nausea remains a significant burden to cancer patients. While some studies indicate that expecting nausea is predictive of experiencing nausea, there are a number of conflicting findings.

This meta-analysis was undertaken to assess the efficacy and safety of drug-eluting stents (DESs) compared to bare metal stents (BMSs) in saphenous vein graft (SVG) interventions. DESs decrease the risk of target vessel revascularization in native coronary arteries compared to BMSs. The ideal treatment strategy in patients with SVG disease is unknown. A search of the published reports was conducted to identify studies that compared DESs and BMSs in SVG intervention with a minimum follow-up of 6 months. A total of 19 studies (2 randomized trials and 17 registries), including 3,420 patients who had undergone SVG intervention (DESs, n = 1,489 and BMS, n = 1,931), met the selection criteria. The mean length of follow-up was 20 + or - 12 months. Using the fixed effect model, target vessel revascularization was less frequently performed in patients who had undergone SVG intervention with a DES than with a BMS (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49 to 0.72). The incidence of myocardial infarction was lower in patients with a DES than in those with a BMS (OR 0.69, 95% CI 0.49 to 0.99). No differences were found in the risk of death (OR 0.78, 95% CI 0.59 to 1.02) or stent thrombosis (OR 0.41, 95% CI 0.15 to 1.11) between the 2 groups. In conclusion, these findings support the use of DESs in SVG lesions.

Moxibustion is a traditional Chinese method that uses the heat generated by burning herbal preparations containing Artemisia vulgaris to stimulate acupuncture points. Considering moxibustion is closely related to acupuncture, it seems pertinent to evaluate the effectiveness of moxibustion as a treatment of symptoms of cancer. The objective of this review was to systematically assess the effectiveness of moxibustion for supportive cancer care.

Randomized controlled trials (RCTs) have reported conflicting results on the impact of high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT) as the first-line treatment for patients with aggressive non-Hodgkin lymphoma (NHL). We performed a systematic meta-analysis to assess the efficacy of HDCT compared to conventional chemotherapy in patients with aggressive NHL with regard to overall survival (OS) at 3 years. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 11/2008) searches. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random effect model. Fourteen RCTs were identified that were published in full text and included a total of 2,413 patients. There was evidence that HDCT showed decreased OS (HR 1.20, 95% CI 1.05-1.37, P=0.006) at 3 years when compared with conventional chemotherapy. The variation in OS probabilities between studies was not statistically significant (test for heterogeneity, Q=10.14, df=13, P=0.683). Thus, our meta-analysis showed that HDCT in aggressive non-Hodgkin lymphoma had decreased overall survival outcome compared with conventional chemotherapy.

The previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.

Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib.

Life-threatening diarrhoea is observed in up to 25% of cancer patients receiving irinotecan. The associations between the UGT1A1*28 polymorphism and irinotecan-induced diarrhoea remains controversial because of conflicting data in the literature. Meta-analyses were performed on published data in terms of relationships between UGT1A1*28 and severe diarrhoea. We searched databases for relevant studies that were published in English or Chinese. Two reviewers extracted data and assessed methodological quality. UGT1A1*28 related odds ratios (ORs) were pooled by use of a fixed-effects model. The studies included were stratified into subgroups representing different races and irinotecan doses, and meta-regression analyses were performed to investigate the effect of study characteristics on the association between UGT1A1*28 and diarrhoea. Twenty trials including a total of 1760 cancer patients were included. The risk of severe diarrhoea at medium and high irinotecan doses was higher among patients with a UGT1A1*28/*28 genotype than among those with a UGT1A1*1/*1 genotype (OR=3.69, 95% confidence interval [CI]=2.00-6.83; P<0.001). Considering the patients with a UGT1A1*1/*28 genotype, the risk of toxicity was also higher than among those with a wild-type genotype at medium and high doses (OR=1.92, 95% CI=1.31-2.82; P=0.001). No association was observed between UGT1A1*28 and severe diarrhoea at low doses (<125 mg/m(2)). In conclusion, patients carrying UGT1A1*28 allele(s) are at an increased risk of irinotecan-induced severe diarrhoea. This increased risk is only apparent in those who are administrated with medium or high irinotecan doses.

There is clear evidence from two systematic reviews that radiotherapy (RT) reduces the risk of local recurrence in patients with resectable rectal cancer, though the data on survival are still equivocal.

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

Non-small-cell lung cancer (NSCLC) accounts for more than 85% of all cases of lung cancer. The 5-year survival of patients presenting with advanced stage NSCLC is less than 15%, indicating that additional treatment options are needed. Bevacizumab is a recombinant humanized version of the murine anti-human vascular endothelial growth factor (VEGF) monoclonal antibody with a high binding specificity for VEGF.

Multigene assays have been developed and validated to determine the prognosis of breast cancer. In this study, we assessed the additional predictive value of the 70-gene MammaPrint signature for chemotherapy (CT) benefit in addition to endocrine therapy (ET) from pooled study series. For 541 patients who received either ET (n = 315) or ET + CT (n = 226), breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) at 5 years were assessed separately for the 70-gene high and low risk groups. The 70-gene signature classified 252 patients (47%) as low risk and 289 (53%) as high risk. Within the 70-gene low risk group, BCSS was 97% for the ET group and 99% for the ET + CT group at 5 years with a non-significant univariate hazard ratio (HR) of 0.58 (95% CI 0.07-4.98; P = 0.62). In the 70-gene high risk group, BCSS was 81% (ET group) and 94% (ET + CT group) at 5 years with a significant HR of 0.21 (95% CI 0.07-0.59; P < 0.01). DDFS was 93% (ET) versus 99% (ET + CT), respectively, in the 70-gene low risk group, HR 0.26 (95% CI 0.03-2.02; P = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17-0.71; P < 0.01). Results were similar in multivariate analysis, showing significant survival benefit by adding CT in the 70-gene high risk group. A significant and clinically meaningful benefit was observed by adding chemotherapy to endocrine treatment in 70-gene high risk patients. This benefit was not significant in low risk patients, who were at such low risk for recurrence and cancer-related death, that adding CT does not appear to be clinically meaningful.

Hypertension is associated with the use of bevacizumab, an angiogenesis inhibitor widely used in cancer therapy. Currently, the risk of severe hypertension associated with bevacizumab is unclear. We performed a systematic review and meta-analysis of published randomized-controlled clinical trials (RCTs) to assess the risk of high-grade hypertension in cancer patients treated with bevacizumab.