Vandetanib with FOLFIRI in patients with advanced colorectal adenocarcinoma: results from an open-label, multicentre phase I study.

PURPOSE: The safety and tolerability of vandetanib (ZACTIMA; ZD6474) plus FOLFIRI was investigated in patients with advanced colorectal cancer (CRC). METHODS: Patients eligible for first- or second-line chemotherapy received once-daily oral doses of vandetanib (100 or 300 mg) plus 14-day treatment cycles of FOLFIRI. RESULTS: A total of 21 patients received vandetanib 100 mg (n = 11) or 300 mg (n = 10) + FOLFIRI. Combination therapy was well tolerated at both vandetanib dose levels. There were no DLTs in the vandetanib 100 mg cohort and one DLT of hypertension (CTCAE grade 3) in the 300 mg cohort. The most common adverse events were diarrhoea (n = 20), nausea (n = 12) and fatigue (n = 10). Two patients (one in each cohort) discontinued vandetanib due to adverse events (rash, 100 mg cohort; hypertension, 300 mg cohort). There was no apparent pharmacokinetic interaction between vandetanib and FOLFIRI. Preliminary efficacy results included two confirmed partial responses in the 100 mg cohort and 9 patients with stable disease > or =8 weeks (100 mg, n = 7; 300 mg, n = 2). CONCLUSIONS: Once-daily vandetanib (100 or 300 mg) in combination with a standard FOLFIRI regimen was generally well tolerated in patients with advanced CRC.status: publishe

Optimal Placement of STATCOMs Against Short-Term Voltage Instability

Short-term voltage stability is an increasing concern in today's power systems given growing penetration of induction motors. The instability can lead to catastrophic consequences such as cascading failures and/or wide-spread blackouts. STATCOMs are able to provide rapid and dynamic reactive power (VAr) support into the system and therefore improve system's short-term voltage performance following a large disturbance. Importantly, the sizing and locating of the STATCOM integration determine how much the short-term voltage performance can be improved. This chapter presents a novel systematic method for optimal placement of STATCOMs against short-term voltage instability. The problem is formulated as a multi-objective optimization model minimizing two conflicting objectives: (1) total investment cost and (2) expected unacceptable short-term voltage performance subject to a set of probable contingencies. Indices for quantifying short-term voltage stability and the related risk level are proposed for problem modeling. Candidate buses for STATCOM installations are analytically selected based on trajectory sensitivity technique. Load dynamics are fully considered using a composite load model comprising induction motor and other typical components. For the proposed model, rather than a single solution, a set of trade-off solutions called Pareto optimal solutions can be obtained, and the decision-maker may select one from them depending on practical needs. A relatively new and superior multiobjective evolutionary algorithm called multi-objective evolutionary algorithm based on decomposition (MOEA/D) is introduced and employed to find the Pareto optimal solutions to the model. The proposed method is verified on the New England 10-machine 39-bus system using industry-grade simulation tool and system models. Simulation results have validated the effectiveness of the proposed method. The method can be practically applied to provide decision-support for STATCOM installations

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy

<p>Background: Pre-treatment weight loss (WL) is a prognostic indicator for overall survival (OS) in head and neck cancer (HNC) patients. This study investigates the association between WL before or during radiotherapy and disease-specific survival (DSS) in HNC patients.</p><p>Methods: In 1340 newly diagnosed HNC patients, weight change was collected before and during (adjuvant) radiotherapy with curative intent. Critical WL during radiotherapy was defined as >5% WL during radiotherapy or >7.5% WL until week 12. Differences in 5-year OS and DSS between WL groups were analysed by Cox's regression with adjustments for important socio-demographic and tumour-related confounders.</p><p>Results: Before radiotherapy, 70% of patients had no WL, 16% had 5-10% WL, and 5% had >10% WL. Five-year OS and DSS rates for these groups were 71%, 59%, 47%, and 42% (P10% WL before radiotherapy remained significantly associated with a worse OS (HR 1.7; 95% CI 1.2-2.5; P = 0.002) and DSS (HR 2.1; 95% CI 1.2-3.5; P = 0.007). The 5-year OS and DSS rates for patients with critical WL during radiotherapy were 62% and 82%, compared with 70% and 89% for patients without critical WL (P = 0.01; P = 0.001). After adjustment, critical WL during radiotherapy remained significantly associated with a worse DSS (HR 1.7; 95% CI 1.2-2.4; P = 0.004).</p><p>Conclusion: Weight loss both before and during radiotherapy are important prognostic indicators for 5-year DSS in HNC patients. Randomised studies into the prognostic effect of nutritional intervention are needed.</p>