Safety analysis of weekly paclitaxel plus S-1 versus paclitaxel plus 5-fluorouracil/calcium folinate as first-line therapy in advanced gastric cancer: a multicenter open random phase II trial.

PURPOSE: To report the results of a safety analysis from a phase II trial comparing administration of weekly paclitaxel plus S-1 (TS) versus paclitaxel plus 5-fluorouracil (5-FU)/calcium folinate (LV) (TLF) as first-line therapy for advanced gastric cancer. METHODS: Patients (n = 240) with previously untreated advanced gastric cancer were randomly assigned to receive either TS or TLF in a 28-day cycle for six cycles. RESULTS: The clinical features of both sets of patients were similar, with the exception of the incidence of prior chemotherapy (P>0·05). Most treatment-related adverse events occurred at similar rates in both treatment arms. However, patients receiving TS experienced an increase in all-grade especially grade 3/4 neutropenia, with an incidence of 43·7% in the TS arm and 16·3% in the TLF arm, respectively (P<0·05). Other severe adverse events were infrequent and not significantly different between the groups. CONCLUSION: The safety and tolerance of weekly paclitaxel plus S-1 or 5-FU/LV is well in untreated advanced gastric cancer patients.

[A phase II prospective randomized controlled trial of weekly paclitaxel combined with S-1 or fluorouracil for advanced gastric carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma. METHODS: Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed. RESULTS: Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different. CONCLUSIONS: Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

The antifibrosis effect of adrenomedullin in human lung fibroblasts.

Adrenomedullin (AM) is a regulatory peptide involved in cellular proliferation and protein synthesis. The authors investigated AM and the AM receptor system in the human fetal lung fibroblasts (HFLFs), and assessed whether AM can inhibit proliferation and collagen synthesis in HFLFs under hypoxia. Fibroblasts were exposed to hypoxia (2% O(2)) after the addition of AM. The effects of AM and transforming growth factor ß1 (TGF-ß1) on the proliferation of fibroblasts were determined by the methanethiosulfonate (MTS) assay. Total collagen synthesis was determined by [(3)H]proline incorporation. TGF-ß1 levels in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of intracellular calciumion ([Ca(2+)](i)) in fibroblasts was detected with a laser scanning confocal microscope. AM, adrenomedullin receptor (ADMR), calcitonin receptor-like receptor (CRLR), AM receptor chaperone receptor activity-modifying protein-1 (RAMP1),RAMP2, and RAMP3 were detected in the HFLFs. The hypoxia-induced increases in cell proliferation, collagen synthesis, and TGF-ß1 production were inhibited by AM. AM also inhibited proliferation and collagen synthesis in fibroblasts induced by TGF-ß1. AM caused a decrease of the hypoxia-induced [Ca(2+)](i) in fibroblasts. This study suggests that AM is produced by HFLFs and AM may function as an antifibrosis factor that protects cells from hypoxic pulmonary damage through its receptors.

[Effect of vaginal administration of controlled-release oxycodone on cancer pain].

BACKGROUND AND OBJECTIVE: Controlled-release oxycodone is an orally administered strong opioid analgesic for moderate to severe cancer pain. Sometimes, its oral administration has to be stopped because of continuous nausea, vomiting, conscious disturbance, or inability to swallow. This study was to investigate analgesic effect of vaginal administration of controlled-release oxycodone on cancer pain and observe adverse events to provide a new choice for female patients who can not tolerate the adverse events caused by oral administration. METHODS: Controlled-release oxycodone tablets were vaginally administered to 36 female patients with moderate to severe cancer pain. The initial dose was 10 mg every 12 h to patients who had never taken opioid analgesics; former dose continued to patients switching to vaginal route from oral route. RESULTS: Among the 36 patients, six had complete relief of cancer pain, 20 had significant relief, four had moderate relief, and four had slight relief, two had no relief. The relief rate of cancer pain was 83.3%. The mean time for onset of analgesic effect was 49 min; the mean duration of analgesic effect was 13.8 h. Main adverse event was vaginal burning sensation in nine (25.0%) patients. No patient discontinued vaginal administration because of adverse events. CONCLUSION: The vaginal administration of controlled-release oxycodone is a safe,effective and simple means of managing cancer pain in female patients who can not tolerate the adverse events caused by oral administration.

A new modified dura mater implant: characteristics in recipient dogs.

Duraplasty is critical to the maintenance of anatomical integrity and the protection of brain tissue. Allotransplantation of cadaveric dura mater was abandoned after it was found to transmit Creutzfeldt-Jakob disease (CJD). In this study, the usefulness of a xenogeneic dura mater for dural reconstruction was tested. Twelve dogs were randomly assigned to 4 groups. To simulate the condition of patients with brain surface injury, an area of approximately 2 cm x 1.5 cm of the dura mater was removed to create a defect. Xenogeneic dura mater derived from porcine pericardium was trimmed to the shape and size of the defect and sutured to the endogenous dura mater. Muscles at the apex of the skull and scalp were also sutured. Three dogs were euthanized at 3, 6, 9, and 12 months after implantation and the xenogeneic dura mater and surrounding endogenous tissue were examined macroscopically and microscopically. Three months after implantation, the graft site had begun to heal. Macroscopically, at 6, 9, and 12 months after implantation, the graft had healed completely with the surrounding tissue. No boundary between the graft and surrounding tissue was distinguishable, and the two could not be separated. The graft was smoothly epithelialized and nonadherent to the brain surface. Microscopically, the inner surface of the implant was covered with epithelial cells, and internal capillaries, subepithelial fibrous tissue deposition, and fibroblast proliferation were observed. The xenogeneic dura mater progressively degraded over time. No cysts and no neutrophilic or lymphocytic inflammatory cell response developed between the implant and the recipient brain parenchyma. The modified xenogeneic dura mater is sufficiently biocompatible to allow epithelialization of its inner surface without adherence to brain tissue. No abnormalities develop in recipients, and the xenograft is gradually biodegraded and replaced by endogenous tissue identical to the endogenous dura mater.

[Changes of pulmonary tissue area density and their mechanisms in rats with hypoxic pulmonary hypertension].

OBJECTIVE: To investigate the changes of pulmonary tissue area density and their mechanisms in rats with hypoxic pulmonary hypertension (HPH). METHODS: 54 Wistar rats were divided into hypoxia 10 d (n = 12), 20 d (n = 12), 30 d (n = 12) groups and control group (n = 18). The rats in hypoxia groups were exposed to a simulated hypoxia environment at a height of 5 km above sea level to establish HPH models. The changes in pulmonary tissue area density and pathological morphology were determined by image analysis, optical microscope, electron microscope and histochemistry. RESULTS: After hypoxia, the pulmonary tissue area density markedly increased on 10 d (27.08% +/- 1.29%, P < 0.05), especially on 20 d (31.33% +/- 0.27%) and 30 d (31.10% +/- 1.95%) while that in control group was 22.78% +/- 1.17% (P < 0.01). The area density on 20 d was higher than that on 10 d (P < 0.05) but there wasn't significantly different between 10 d and 30 d (P = 0.057) after hypoxia. Pathological examination showed: edema and collapse of pulmonary tissue, swelling and degeneration of type II alveolus epithelial cells (PII); congestion, accumulation of polymorphonuclear neutrophils and platelets in capillaries; swelling and degeneration of endothelial cells, thickening of basement membranes. CONCLUSIONS: Hypoxia can induce increase in pulmonary tissue area density and decrease in aerial exchange area in alveoli. These changes may be related to the pulmonary collapse caused by the damage of PII and pulmonary surfactant system, structural remodeling of small pulmonary arteries, increase in blood cells and protein granules in alveolar cavity.