To define the efficacy of gefitinib in chemotherapy-naive patients with advanced non-small cell lung cancer, we carried out a meta-analysis of randomised controlled trials. Medline, Embase, the Cochrane controlled trials register and the Science Citation Index were searched. Seven trials were identified, covering a total of 4656 subjects. As compared with chemotherapy, gefitinib was effective in the selected patients: the corresponding summary hazard ratios (gefitinib versus chemotherapy) for progression-free survival were 0.43 (0.32, 0.58) (P < 0.001) for the subgroup of patients with epidermal growth factor receptor (EGFR) mutant treated with gefitinib monotherapy, 0.71 (0.60, 0.83) (P < 0.001) for the subgroup of patients with lung adenocarcinoma; but was detrimental for the patients without EGFR mutant treated by gefitinib monotherapy [hazard ratio = 2.16 (1.17, 3.99), P = 0.01]. Significantly improved survival was found in the gefitinib group compared with the control in the subgroup of patients with lung adenocarcinoma [hazard ratio = 0.89 (0.81, 0.99); P = 0.03], but not found in the subgroup of patients with EGFR mutant [hazard ratio = 0.87 (0.68, 1.12); P = 0.28]. In conclusion, first-line treatment with gefitinib conferred prolonged progression-free survival than treatment with systemic chemotherapy in a molecularly or histologically defined population of patients with non-small cell lung cancer, and improved survival in the subgroup of patients with lung adenocarcinoma.

The purpose of this study was to assess the efficacy and toxicity of vandetanib in the second-line treatment for advanced non-small cell lung cancer (NSCLC).

This meta-analysis aimed to investigate the effects of beta-carotene supplements alone on cancer prevention as reported by randomized controlled trials (RCTs). We searched PubMed, EMBASE, and CENTRAL. Among the 848 articles searched, 6 randomized controlled trials, including 40,544 total participants, 20,290 in beta-carotene supplement groups, and 20,254 in placebo groups, were included in the final analysis. In a meta-analysis of 6 RCTs, beta-carotene supplements had no preventive effect on either cancer incidence [relative risk (RR) = 1.08, 95% confidence interval (CI) = 0.99-1.18] or cancer mortality (RR = 1.00, 95% CI = 0.87-1.15). Similar findings were observed in both primary prevention trials and secondary prevention trials. Subgroup analyses by various factors revealed no preventive effect of beta-carotene supplementation on cancer prevention and that it significantly increased the risk of urothelial cancer, especially bladder cancer (RR = 1.52, 95% CI = 1.03-2.24) and marginally increased the risk of cancer among current smokers (RR = 1.07, 95% CI = 0.99-1.17). The current meta-analysis of RCTs indicated that there is no clinical evidence to support the overall primary or secondary preventive effect of beta-carotene supplements on cancer. The potential effects, either beneficial or harmful, of beta-carotene supplementation on cancer should not be overemphasized.

Iron supplementation could improve the hematopoietic response of erythropoiesis-stimulating agents (ESAs) used for chemotherapy-induced anemia.

Capecitabine- and 5-fluorouracil (5-FU)-based regimens are widely used for the treatment for advanced gastric cancer (AGC). We aimed to compare the efficacy of the two regimens for both Caucasian and Asian subjects, through a meta-analysis of the available trial evidence.

Clinical trials conducted over the last two decades have demonstrated that 5 years of treatment with tamoxifen (TAM) after local treatment in postmenopausal patients with positive hormone receptor early breast cancer improves disease-free survival and overall survival. More recently, aromatase inhibitors (AI) have been tested in several randomized clinical trials in this setting. The studies have tested either AI versus TAM or different sequential approaches combining the two agents. While the most effective strategy remains to be determined, overall, incorporation of AI resulted in better disease-free survival, particularly in the worst-prognosis subgroup of patients. In addition, long-term treatment with AI was, in general, well tolerated. However, mature results are needed in order to be able to assess the effect in overall survival. The authors of this supplement paper include the key points of roundtable presentations and discussions of hormonal therapy in breast cancer by topic.

To assess the role of the novel second-line treatments in nonsmall cell lung cancer (NSCLC).

Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity.

Many women with ovarian cancer eventually develop resistance to conventional chemotherapy drugs, and so novel agents are being developed to target specific molecular pathways. One such class of drugs inhibits angiogenesis (the development of new blood vessels), which is essential for tumour growth. It is important to establish whether the addition of these new drugs to conventional chemotherapy regimens improves survival, and what the side-effects may be.

The typical class side effect of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (panitumumab and cetuximab) is a cutaneous maculopapular rash, although hypomagnesemia is also described to be a frequent adverse event. The purpose of our meta-analysis is to evaluate the frequency and the relative risk of hypomagnesemia in patients treated with cetuximab or panitumumab in randomized trials.

A central goal of gene expression studies coupled with drug response screens is to identify predictive profiles that can be exploited to stratify patients. Numerous methods have been proposed towards this end, most of them focusing on novel statistical methods and model selection techniques that attempt to uncover groups of genes, whose expression profiles are directly and robustly correlated with drug response. However, biological systems process information through the crosstalk of multiple signaling networks, whose ultimate phenotypic consequences may only be determined by the combined input of relevant interacting systems. By restricting predictive signatures to direct gene-drug correlations, biologically meaningful interactions that may serve as superior predictors are ignored. Here we demonstrate that predictive signatures, which incorporate the interaction between background gene expression patterns and individual predictive probes, can provide superior models than those that directly relate gene expression levels to pharmacological response, and thus should be more widely utilized in pharmacogenetic studies.

Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma (RCC) and GI stromal tumor. Congestive heart failure (CHF) is an important adverse effect that has been reported with sunitinib, but overall incidence and relative risk (RR) remain undefined. We performed an up-to-date meta-analysis to determine the risk of developing CHF in patients with both RCC and non-RCC tumors treated with sunitinib.

As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen.

To perform a meta-analysis in order to quantify the actual cumulative randomized evidence for the benefit and toxicity of trastuzumab combined with neoadjuvant chemotherapy in HER2-positive breast cancer.

Discovery of the over-expression of Her-2/neu or the amplification of its regulatory gene in stomach and esophageal cancer has resulted in targeted treatment directed at this protein. The fact itself and its consequences have been the topic of an abundance of studies and clinical trials. In the present report we review the current state of the art as regards diagnosis of the over-expression and amplification of Her-2/neu, its inhibition as a new therapeutic concept, treatment toxicity, and the development of resistance to Her-2/neu as a limiting factor in stomach and esophageal adenocarcinoma.

Imatinib at a dose of 400 mg daily is considered frontline treatment in chronic phase chronic myeloid leukemia (CP-CML). We conducted a systematic review and meta-analysis of randomized controlled trials comparing frontline treatment with imatinib 400 mg daily versus higher doses (≥600 mg daily) in patients with CP-CML. The search yielded four trials, randomizing 1,673 patients. At 12 months, high dose compared with standard dose imatinib improved complete cytogenetic response (CCyR) (RR 1.17, 95% CI 1.08-1.26, four trials, I(2) = 33%) as well as major molecular response (MMolR) (RR 1.26, 95% CI 1.12-1.42, four trials, I(2) = 0%). There was no difference in all-cause mortality or disease progression at the end of follow up. Adverse events requiring discontinuation were more common in the high-dose arm (RR 1.98, 95% CI 1.20-3.26, three trials, I(2) = 0%), as were Grade III/IV neutropenia and thrombocytopenia: RR 1.56, 95% CI 1.15-2.12 and RR 1.86, 95% CI 1.28-2.70, respectively. There is currently insufficient evidence to support the routine use of higher doses of imatinib as frontline treatment for CP-CML. Extended follow up is needed to evaluate if the superior CCyR and MMolR with higher doses of imatinib will translate to long-term clinical benefit.

Aromatase inhibitors are associated with consistent improvements in disease-free survival but not in overall survival. We conducted a literature-based meta-analysis of randomized trials to examine whether the relative toxicity of aromatase inhibitors compared with tamoxifen may explain this finding.

Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies it is important to know the risk of, and associated risk factors for, hepatic late adverse effects.

Randomized controlled trials (RCTs) of multikinase inhibitors sunitinib, sorafenib, and pazopanib have reported efficacy compared with results from placebo and interferon-α (INF-α). To date, these drugs have not been compared in head-to-head trials.

Since the introduction of chemotherapy, survival in localised high-grade osteosarcoma has improved considerably. However, there is still no worldwide consensus on a standard chemotherapy approach. In this systematic review evidence for effectiveness of each single drug and the role of response guided salvage treatment of adjuvant chemotherapy are addressed, whereas in a meta-analysis the number of drugs in current protocols is considered.