Weekly oral paclitaxel as first-line treatment in patients with advanced gastric cancer.

BACKGROUND: Pharmacokinetic study has shown that co-administration of cyclosporin A (CsA), which acts as a P-glycoprotein (P-gp) and CYP-3A blocker, resulted in an 8-fold increase in the systemic exposure of oral paclitaxel. Two doses of oral paclitaxel on 1 day in combination with CsA resulted in higher systemic exposure than single dose administration. PATIENTS AND METHODS: In this phase II study, chemonaïve patients with advanced gastric cancer received oral paclitaxel weekly in two doses of 90 mg/m(2) on the same day; CsA (10 mg/kg) was given 30 min before each dose of oral paclitaxel. RESULTS: In 25 patients, the main toxicities were: nausea CTC grade 2/3, 10 patients (40%); vomiting grade 2/3, 4 patients (20%); diarrhea grade 2/3, 6 patients (24%); neutropenia grade 3/4, 5 patients (20%). In the 24 evaluable patients, eight partial responses were observed, resulting in an overall response rate (ORR) of 33% [95% confidence interval (CI) 18% to 52%]. Eleven patients had stable disease (46%) and 5 patients showed progressive disease (21%). The ORR in the total population was 32% (95% CI 17% to 50%). The median time to progression was 16 weeks (95% CI 9-22). Pharmacokinetic analyses revealed that the mean area under the plasma concentration-time curve (AUC) of orally administered paclitaxel (+/- standard deviation) was 3757.6 +/- 939.4 ng.h/ml in week 1 and 3928.4 +/- 1281 ng.h/ml in week 2. The intrapatient variability in the AUC was 12%. CONCLUSIONS: Oral paclitaxel in combination with CsA is both active and safe in chemonaïve patients with advanced gastric cancer. Toxicities were mainly gastrointestinal.

Synthesis, spectroscopy and catalysis of

Chromium acetyl acetonate [Cr(acac)3] complexes have been grafted onto the surface of two mesoporous crystalline materials; pure silica MCM-41 (SiMCM-41) and Al-containing silica MCM-41 with an Si:Al ratio of 27 (AlMCM-41). The materials were characterized with X-ray diffraction, N2 adsorption, thermogravimetrical analysis, diffuse reflectance spectroscopy in the UV-Vis-NIR region (DRS), electron spin resonance (ESR) and Fourier transform infrared spectroscopy. Hydrogen bonding between surface hydroxyls and the acetylacetonate (acac) ligands is the only type of interaction between [Cr(acac)3] complexes and SiMCM-41, while the deposition of [Cr(acac)3] onto the surface of AlMCM-41 takes place through either a ligand exchange reaction or a hydrogen-bonding mechanism. In the as-synthesized materials, Cr3+ is present as a surface species in pseudo-octahedral coordination. This species is characterized by high zero-field ESR parameters D and E, indicating a strong distortion from O(h), symmetry. After calcination, Cr3+ is almost completely oxidized to Cr6+, which is anchored onto the surface as dichromate, some chromate and traces of small amorphous Cr2O3 clusters and square pyramidal Cr5+ ions. These materials are active in the gas-phase and slurry-phase polymerization of ethylene at 100 degrees C. The polymerization activity is dependent on the Cr loading, precalcination temperature and the support characteristics: a 1 wt % [Cr(acac)3]-AlMCM-41 catalyst pretreated at high temperatures was found to be the most active material with a polymerization rate of 14000 g polyethylene per gram of Cr per hour. Combined DRS-ESR spectroscopies were used to monitor the reduction process of Cr(6+/5+) and the oxidation and coordination environment of Cr(n+) species during catalytic action. It will be shown that the polymer chains initially produced within the mesopores of the Cr-MCM-41 material form nanofibres of polyethylene with a length of several microns and a diameter of 50 to 100 nanometers. These nanofibres (partially) cover the outer surface of the MCM-41 material. The catalyst particles also gradually break up during ethylene polymerization resulting in the formation of crystalline and amorphous polyethylene with a low bulk density and a melt flow index between 0.56 and 1.38g per 10 min; this indicates the very high molecular weight of the polymer.

Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature.

Ifosfamide is an alkylating agent used in the treatment of a variety of solid tumours. Ten to 15% of patients treated with ifosfamide develop an encephalopathy. Methylene blue (MB) may be used in the treatment of this encephalopathy. The purpose of this study was to evaluate the neuroprotective effect of MB in these patients and to review the literature. Between 1993 and 1997, 52 patients (age 16-77 years) with solid tumours were treated with ifosfamide in dosages ranging from 3 to 5 g m(-2) q3w when given in combination schedules and up to 12 g m(-2) q4w when given as a single agent. Twelve patients developed central nervous system (CNS) depression, defined as National Cancer Institute Common Toxicity Criteria (NCI-CTC) neurocortical toxicity grade 2 or higher. Eight were treated with MB at a dose of 6 x 50 mg day(-1) intravenously (i.v.). Four recovered fully within 24 h, two recovered partially after 24 h and completely after 48 h while two recovered only after 72 h. Four patients did not receive MB and all recovered only after 48 h. Three patients received prophylaxis with MB at a dose of 4 x 50 mg day(-1) i.v. for the subsequent chemotherapy cycles. Two developed milder encephalopathy; one had no CNS depression at all. We conclude that MB is an effective treatment for ifosfamide-induced encephalopathy. Our findings suggest that it may also be used as a prophylactic agent.