Efficacy and Tolerability of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer After Moderately Emetogenic Chemotherapy

PURPOSE: This is the first study in which the NK(1)-receptor antagonist, aprepitant (APR), was evaluated for the prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy. PATIENTS AND METHODS: Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide +/- doxorubicin or epirubicin. Patients were randomly assigned to either an aprepitant regimen (day 1, APR 125 mg, ondansetron (OND) 8 mg, and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, APR 80 qd) [DOSAGE ERROR CORRECTED] or a control regimen (day 1, OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, OND 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary. The primary efficacy end point was the proportion of patients with complete response, defined as no vomiting and no use of rescue therapy, during 120 hours after initiation of chemotherapy in cycle 1. The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis questionnaire. RESULTS: Of 866 patients randomized, 857 patients (99%) were assessable. Overall complete response was greater with the aprepitant regimen than with the control regimen (50.8% v 42.5%; P = .015). More patients in the aprepitant group reported minimal or no impact of CINV on daily life (63.5% v 55.6%; P = .019). Both treatments were generally well tolerated. CONCLUSION: The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide.published_or_final_versio

New insight into kinetics behavor of the structural formation process in Agar gelation

A time-resolved experimental study on the kinetics and relaxation of the structural formation process in gelling Agar-water solutions was carried out using our custom-built torsion resonator. The study was based on measurements of three naturally cooled solutions with agar concentrations of 0.75%, 1.0% and 2.0% w/w. It was found that the natural-cooling agar gelation process could be divided into three stages, sol stage (Stage I), gelation zone (Stage II) and gel stage (Stage III), based on the time/temperature evolutions of the structural development rate (SDR). An interesting fluctuant decaying behavior of SDR was observed in Stage II and III, indicative of a sum of multiple relaxation processes and well described by a multiple-order Gaussisn-like equation: . More interestingly, the temperature dependences of the fitted values of Wn in Stage II and Stage III were found to follow the different Arrhenius laws, with different activation energies of EaII= 39-74 KJ/mol and EaIII~7.0 KJ/mol. The two different Arrhenius-like behaviors respectively suggest that dispersions in Stage II be attributed to the relaxation of the self-assembly of agar molecules or the growth of junction zones en route to gelation, in which the formation or fission of hydrogen bonding interactions plays an important role; and that dispersions in Stage III be attributed to the relaxation dynamics of water released from various size domains close to the domain of the viscous flow of water during the syneresis process.Comment: 24 pages, 4 figures, 1 tabl

Comparison between gamma and beta irradiation effects on hydroxypropylmethylcellulose and gelatin hard capsules

The effects of electron beam or λ-irradiation on technological performances (capsule hardness, expressed as deforming work and dissolution time) of empty 2-shell capsules made of gelatin or hydroxypropylmethylcellulose (HPMC) were studied. Capsule structural changes induced by radiation treatment were investigated by capillary viscometry and atomic force microscopy (AFM). The capsules were irradiated in the air at 5, 15, and 25 kGy. The deforming work of nonirradiated HPMC capsules (0.06±0.01 J) was lower than that of gelatin capsules (0.10±0.01 J). The dissolution time of the HPMC capsules (414±33 seconds) was slightly higher than that determined for gelatin hard capsules (288±19 seconds). The hardness and dissolution time of gelatin and HPMC capsules were not significantly influenced by the irradiation type and the applied irradiation dose. As the viscometry analyses are concerned, irradiation caused a reduction of the intrinsic viscosity and water and dimethyl sulfoxide solvent power in both the cases. AFM analysis showed that the radiation treatment did not appreciably affect the surface roughness of the samples nor induce structural changes on capsule surface. However, measurements of force-distance curves pointed out a qualitative parameter for the identification of the irradiated capsules. On the bases of these preliminary results, empty gelatin or HPMC hard capsules can be sanitized/sterilized by ionizing radiation