Annals of oncology : official journal of the European Society for Medical Oncology
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Review Meta Analysis
Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials.
Aromatase inhibitors (AIs) have been associated with cardiovascular disease in adjuvant randomized controlled trials (RCTs) comparing these drugs to tamoxifen. However, it is unclear whether this risk is real or due to cardioprotective effects of tamoxifen. To address this question, we conducted a systematic review and meta-analysis of all RCTs of AIs and tamoxifen in adjuvant and extended adjuvant setting. ⋯ The increased risk of cardiovascular events with AIs relative to tamoxifen is likely the result of cardioprotective effects of the latter. This new evidence should be considered when assessing the benefits and risks of AIs in the treatment of breast cancer.
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Based upon preclinical synergy in murine models, we carried out a phase I trial to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and biomarkers of response for the combination of BKM120, a PI3K inhibitor, and olaparib, a PARP inhibitor. ⋯ BKM120 and olaparib can be co-administered, but the combination requires attenuation of the BKM120 dose. Clinical benefit was observed in both gBRCAm and gBRCAwt pts. Randomized phase II studies will be needed to further define the efficacy of PI3K/PARP-inhibitor combinations as compared with a PARP inhibitor alone.
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Multicenter Study Clinical Trial
Multimodality treatment for esophageal adenocarcinoma: multi-center propensity-score matched study.
The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups. ⋯ The survival differences between NCRS and NCS maybe modest, if present at all, for the treatment of locally advanced esophageal or junctional adenocarcinoma. Future large-scale randomized trials must control and monitor indicators of the quality of surgery, as the extent of lymphadenectomy appears to influence prognosis in patients treated with NCS, from this large multi-center European study.
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The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. ⋯ Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.
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Sorafenib is a multikinase-tyrosine kinase inhibitor commonly used in a variety of cancers. There are concerns about the increased risk of serious adverse events (SAEs) and fatal adverse events (FAEs) with sorafenib. We performed an up-to-date meta-analysis of all phase 3 randomized controlled trials (RCTs) of sorafenib to quantify the increased risk of SAEs and FAEs. ⋯ This meta-analysis of phase 3 RCTs demonstrates an increased risk of both SAEs and FAEs with sorafenib use in adult patients with solid cancers. This quantification of increased risks of SAEs and FAEs will be important in considering the trade-off of sorafenib treatment during shared decision-making.