Capecitabine for locally advanced and metastatic colorectal cancer:A review

Capecitabine (Xeloda) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specif ic conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capecitabine with standard folinic acid (leucovorin, LV)-modulated intravenous 5-fluorouracil (5-FU) bolus regimens in patients with metastatic colorectal cancer. Moreover the efficacy of Capecitabine on metastatic colorectal cancer, either alone or in various combinations with other active drugs such as Irinotecan and Oxaliplatin was also assessed. Finally, neoadjuvant therapy con- sisting of Capecitabine plus radiation therapy, for locally advanced rectal cancer was analysed. This combination of chemotherapy and radiotherapy has a special role in tumor down staging and in sphincter preservation for lower rectal tumors. Comparative trials have shown that Capecitabine is at least equivalent to the standard LV-5-FU combination in relation to progression-free and overall survival whilst showing a better tolerability prof ile with a much lower incidence of stomatitis. It is now known that Capecitabine can be combined with other active drugs such as Irinotecan and Oxaliplatin. The combination of Oxaliplatin with Capecitabine represents a new standard of care for metastatic colorectal cancer. Combinating the Capecitabine-Oxaliplatin regimen with promising new biological drugs such as Bevacizumab seems to give a realistic prospect of further improvement in time to progression of metastatic disease. Moreover, preoperative chemo-radiation using oral capecitabine is better tolerated than bolus 5-FU and is more effective in the promotion of both down-staging and sphincter preservation in patients with locally advanced rectal cancer. Finally, the outcomes of recently published trials suggest that capecitabine seems to be more cost effective than other standard treatments for the management of patients with colorectal cancer.

Direct adaptive regulation of unknown nonlinear systems with analysis of the model order problem

A new method for the direct adaptive regulation of unknown nonlinear dynamical systems is proposed in this paper,paying special attention to the analysis of the model order problem.The method uses a neurofuzzy (NF) modeling of the unknown system,which combines fuzzy systems (FSs) with high order neural networks (HONNs).We propose the approximation of the unknown system by a special form of an NF-dynamical system (NFDS),which,however,may assume a smaller number of states than the original unknown model.The omission of states,referred to as a model order problem,is modeled by introducing a disturbance term in the approximating equations.The development is combined with a sensitivity analysis of the closed loop and provides a comprehensive and rigorous analysis of the stability properties.An adaptive modification method,termed ‘parameter hopping’,is incorporated into the weight estimation algorithm so that the existence and boundedness of the control signal are always assured.The applicability and potency of the method are tested by simulations on well known benchmarks such as ‘DC motor’ and ‘Lorenz system’,where it is shown that it performs quite well under a reduced model order assumption.Moreover,the proposed NF approach is shown to outperform simple recurrent high order neural networks (RHONNs).