Areas covered: Herein we review pharmacodynamics and kinetics, clinical data and treatment-related toxicities of bevacizumab in the treatment of metastatic, recurrent or persistent cervical cancer. Additionally, future areas of development are reviewed.
Expert commentary: Anti-angiogenesis therapy with bevacizumab is central to metastatic, persistent, and recurrent cervical cancer treatment. Additional anti-angiogenesis drugs are in development. Future studies will need to establish if the addition of multiple anti-angiogenesis agents or anti-angiogenesis in combination with immunotherapy is more effective than bevacizumab with chemotherapy. 相似文献
Areas covered: Sonidegib is an oral hedgehog pathway inhibitor with a novel structure. It has recently been licensed for the treatment of laBCC.
This article provides a comprehensive review of the literature regarding sonidegib, detailing the pharmacology of the compound, clinical trial data, competitor compounds and a future perspective.
Expert commentary: Sonidegib is a novel smoothened (SMO) inhibitor with comparable efficacy to vismodegib, with patient response rates of 44% (sonidegib) and 43% (vismodegib). The adverse effect profile of these two treatments is similar with the main effects being considered to be class effects of SMO inhibitors. 相似文献
Objective: To determine risk factors for the development of AKI in patients treated for endocarditis.
Methods: This single centre, retrospective univariate and multivariate analysis to determine risk factors for the development of AKI included patients diagnosed with endocarditis between January 2009 and October 2013.
Results: Of 211 included patients, a total of 84 (39.8%) patients developed AKI. We identified multiple independent variables associated with the development of AKI, including: age ≥ 65 years, presence of hardware, chronic kidney disease, AKI on admission, infection with Staphylococcus spp, receipt of nafcillin or oxacillin or aminoglycoside and nafcillin or oxacillin or aminoglycoside and vancomycin, vancomycin trough level ≥ 20.0 mcg/ml, aminoglycoside total daily dose reduction, duration of vancomycin exceeding three days, receipt of loop diuretic or more than three concomitant nephrotoxins and duration of loop diuretic or non-steroidal anti-inflammatory drug therapy exceeding seven days.
Conclusions: In patients treated for endocarditis, multiple risk factors for AKI were identified. Prospective studies are needed to evaluate these variables for causation of AKI in patients treated for endocarditis. 相似文献
Areas covered: This review gives a brief overview of the contemporary clinical data on lenvatinib including its mechanism of action, pharmacokinetics, efficacy and safety profile in combination with everolimus. The clinical applications of lenvatinib in combination with everolimus are addressed within the context of the current competitive therapeutic landscape of RCC.
Expert commentary: Lenvatinib is a new VEGF receptor-targeted tyrosine kinase inhibitor approved in combination with everolimus for second-line therapy in patients with advanced renal cell carcinoma progressing on a first-line VEGF receptor-targeted tyrosine kinase inhibitor. The combination of lenvatinib with everolimus significantly improved progression-free survival compared with everolimus with a hazard ratio of 0.40 and increased objective response to 43%. Optimal sequence of therapy targeting the tumor and the immune system remains a challenge and further investigation is warranted. 相似文献
Methods: Three cases of MWA application in the emergent control of life-threatening hepatic tumour haemorrhage were analysed and reported.
Results: Satisfactory hemostasis for hepatic tumour rupture was achieved by MWA in all three cases. No major complications, such as post-operative haemorrhage, bile duct injury, liver abscess, colon perforation, skin burns, tumour seeding or renal dysfunction, were identified.
Conclusions: MWA may be a feasible, effective and simple strategy for the emergent control of intraoperative hepatic tumour bleeding. To the best of our knowledge, this study represents the first reported cases of this novel application of MWA. 相似文献
Patients and methods: We retrospectively collected data from patients affected by NS-NSCLC treated with platinum plus bevacizumab across Tuscany.
Results: We evaluated 62 (median age: 63.5 [30–77] years) pts. All but one presented with adenocarcinoma and the majority had ECOG PS of 0/1. 17.7% presented with central lesion, 11.3% with brain metastasis, 38.7% with hypertension and 4.8% with mild haemoptysis. We observed a median time to progression (TTP) of 6.5 [2–37] and a median overall survival (OS) of 10.5 [2–39] months. Overall response rate (ORR) was 59.6% with a disease control rate (DCR) of 80.6%. Safety profile was acceptable. We observed five cardiovascular events and two major bleedings with no toxic deaths.
Conclusion: Safety and efficacy real world data are consistent with those from clinical trials even in a less selected population. 相似文献
Areas covered: Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) are involved in the pathogenesis of GC. Clinical studies have evaluated VEGFR-2 blocked in second line. Two phase III trials using ramucirumab alone or associated to paclitaxel have demonstrated that second-line therapy could improve the survival of patients with GC.
Expert commentary: VEGF-2 receptor blockade is effective at treating GC. The combination of paclitaxel with ramucirumab can be used to establish an angiogenic blockade in second-line therapy. The magnitude of the treatment effect suggests that this combination should be used as the current standard. 相似文献
Areas covered: We review the key preclinical and clinical data surrounding its use in the maintenance setting.
Expert commentary: We also consider the market profile, regulatory issues surrounding the agent and offer a five year speculative viewpoint of its future development in ovarian cancer. 相似文献
Objectives: to quantify CTCs and identify CTM as well as the EGF Receptor (EGFR) protein expression in these cells and correlate with clinical outcome in metastatic STS.
Materials and methods: Approximately 8mL of blood was prospectively collected from patients with different types of high-grade STS, before the beginning of chemotherapy. The samples were processed and filtered by ISET (Rarecells, France) for the isolation and quantification of CTCs and CTMs. EGFR expression was analyzed by immunocytochemistry (ICC) on CTCs/ CTMs.
Results: We analyzed 18 patients with median age of 49 years (18-77 y). The positivity for EGFR protein expression in CTCs was observed in 93.75% of the patients. This result shows that targeting EGFR positive CTCs from STS origen can be translated in clinical benefit for some patients. In addition, if target therapy is chosen, the EGFR expression in CTCs can be used in follow-up to measure treatment effectiveness.
Conclusions: This is the first study to demonstrate the expression of EGFR protein in CTCs from sarcoma patients. It may open an area for future investigations. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of EGFR in sustaining tumor metastasis in sarcomas. 相似文献
Objective: We discuss possible options to optimize the management of injured children in light of the available literature findings.
Results: The risk of viral infection is low. However, blood investigations are mandatory, as well as appropriate counselling. Anti-HBV immunoglobulins are recommended in all unvaccinated subjects exposed to a HBsAg-positive source; however, there is no agreement regarding their administration in unvaccinated children. Use of anti-tetanus immunoglobulins in unvaccinated child with minor and clean wound is well defined; however, wound type classification in the event of needlestick injury may be difficult and subjective. There is no agreement on the routine use of antiretroviral prophylaxis.
Conclusion: From a practical point of view, several unsolved issues have emerged regarding the management of the children with needlestick injury, which appear particularly relevant in the anti-vaccination movement era. International guidelines should be encouraged at this regard. 相似文献
A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC.
Methods: We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included.
Results: Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation.
Conclusion: There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed. 相似文献
Methods: A web-based survey was emailed to 63 ROs, who were identified through publications, guideline panel membership, and/or affiliation with institutions of high MCC volume. ROs provided treatment recommendations for two hypothetical case scenarios of early stage MCC.
Results: Among 28 respondents (45%), 26 regularly saw and treated MCC patients for a median 7 years (range, 0–30). While all ROs recommended adjuvant radiation for a stage II upper extremity MCC, only 48% recommended adjuvant radiation for stage I head and neck MCC.
Conclusion: Among US-based MCC RO ‘specialists,’ there is equipoise on the role of radiotherapy for stage I MCC. Ideally, prospective studies are needed to identify which patients may benefit from radiation. 相似文献
significantly decreased mortality from breast cancer (BC).
Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase
recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops.
Expert commentary: Compliance ensures optimal benefit from extended antihormone adjuvant therapy.Retarding acquired resistance using CDK4/6 or mTOR inhibitors is discussed. Preventing acquired resistance from mutations of ER could be achieved with Selective ER Downregulators (SERDs), eg fulvestrant. Fulvestrant is a depot injectable so oral SERDs are sought for extended use. In reality, a ‘super SERD’ which destroys ER but improves women’s health like a Selective ER Modulator (SERM), would aid compliance to prevent recurrence and death. Estrogen-induced apoptosis occurs in 30% of BC with antihormone resistance. The ‘one in three’ rule that dictates that one in three unselected patients respond to either hormonal or antihormonal therapy in BC occurs with estrogen or antiestrogen therapy and must be improved. The goal is to maintain patients for their natural lives by blocking cancer cell survival through precision medicine using short cycles of estrogen apoptotic salvage therapy, and further extended antihormone maintenance. 相似文献
Areas covered: A literature search for recurrent HCC was performed using Medline and PubMed up to May 2016.
Expert commentary: The long term survival results after re-resection for recurrent HCC were favourable and aggressive management of postoperative intrahepatic recurrence remains the most important strategy in prolonging the survival of patients after resection of HCC. 相似文献
Patients and methods: A total of 86 patients were treated with preoperative radiochemotherapy and deep regional hyperthermia at our institution. For every patient, the 5-year probability for death, distant metastases and local failure based on a previously published nomogram were calculated and patients were divided into three risk groups.
Results: Low-lying and clinically lymph node positive tumours were more frequent in the validation cohort. Five-year Kaplan–Meier estimates for overall survival (OS), distant metastases-free survival (DMFS) and local control (LC) were 87.3%, 79.9%, 95.8% (observed) and 75.5%, 71%, 90% (predicted), respectively. Discrimination between low- and high-risk groups was at a significant level for all endpoints. The c-index was 0.81 (OS), 0.67 (DMFS) and 0.92 (LC), respectively.
Conclusions: The nomogram showed reasonable performance when deep regional hyperthermia is incorporated into preoperative therapy. The higher than predicted rates seen for OS and DMFS in particular in the high-risk groups warrant further prospective validation and subsequent investigation of the underlying mechanisms. 相似文献
The results were evaluated both clinically and with the aid of diagnostic imaging techniques during a 5-year follow-up study.
Materials and methods: Eleven patients affected by spinal OB were treated in a single session with biopsy and CT-guided RFA. Pre- and post-evaluations of the patients were performed both clinically and with CT and magnetic resonance imaging (MRI).
Results: Complete success in terms of pain relief was achieved in all patients. Additional treatments were not required in any patients. There were no complications. During follow-up, neither complications nor pathological findings related to the treatment were observed.
Conclusions: Our experience demonstrates that RFA for spinal OB is safe and effective. One of the main advantages of this technique is represented by its lower grade of invasiveness compared with that for potentially hazardous surgical manoeuvres. 相似文献
Methods: All the eligible studies were searched by PubMed, Medline, Embase and the Cochrane Library. The meta-analysis was performed to compare odds ratios (ORs) for overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS).
Results: Eight studies were included in the meta-analysis. Chemotherapy group did not significantly differ from RT group. The pooled OR and 95% confidence interval (CI) for 1-year, 3-year, 5-year and 10-year OS was 1.25 [0.84, 1.87], 1.10 [0.76, 1.58], 0.83 [0.59, 1.17] and 1.05 [0.70, 1.56]. In addition, the combined OR and 95% CI for 5-year DFS and PFS were 0.96 [0.53, 1.73] and 0.71 [0.45, 1.12].
Conclusions: The current evidence suggests that CMT was not superior to RT alone. Radiotherapy may be still the main method in the treatment of early stage nasal NK/T-cell lymphoma. 相似文献
Areas covered: This review provides an overview of available therapeutic strategies after radical cystectomy and examines ongoing clinical trials including cytotoxic chemotherapy and immunotherapy.
Expert commentary: Cytotoxic chemotherapy offers limited benefit in UCUB patients. However, the recent introduction of immunotherapy provides new hope for durable responses or possibly complete cures. 相似文献
Methods: Primary mediastinal sarcomas (1988 - 2013) were assembled from the SEER database. The incidence and 10-year cancer-specific survival rates were compared to other primary mediastinal malignancies (thymic carcinoma, germ cell tumors, neurogenic tumors, Hodgkin / non Hodgkin lymphomas) as well as to non mediastinal sarcomas.
Results: A total of 204 patients were recruited into this cohort. Multivariate analysis showed better overall survival for patients with younger age at diagnosis, low grade [hazard ratio 0.427 (95% CI: 0.224-0.814; P= 0.010)], posterior mediastinum location [hazard ratio 0.458 (95% CI: 0.268-0.781; P= 0.004)], node negative disease [hazard ratio 0.463 (95% CI: 0.232-0.923; P= 0.029)] and surgical treatment [hazard ratio 0.488 (95% CI: 0.336-0.709; P <0.0001)]. Compared to other mediastinal malignancies, primary mediastinal sarcomas have the worst 10-year overall survival. Similarly compared to non mediastinal sarcomas, primary mediastinal sarcomas have worse 10-year overall survival (23% versus 55%).
Conclusion: Primary mediastinal sarcoma is a rare entity with worse prognosis compared to non-mediastinal counterparts. Surgical resection plays a particularly important role in the management. 相似文献
Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of systemic treatment of metastatic colorectal cancer. This article reviews the current evidence for targeted therapies in advanced colorectal cancer, including up-to-date data regarding anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF) agents, the relevance of primary tumor location and novel subgroups such as BRAF mutated, HER2 amplified, and mismatch-repair-deficient cancers.
Expert commentary: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for metastatic colorectal cancer (mCRC). The use of EGFR-targeted antibodies should be restricted to patients with extended RAS wild-type profiles, and there is evidence that they should be further restricted to patients with left-sided tumors. Clinically, mCRC can be divided into subgroups based on RAS, BRAF, HER2, and MMR status, each of which have distinct treatment pathways. 相似文献