Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m2), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m2), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m2), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m2). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P =0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe. 相似文献
Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown.
Methods
Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety.
Results
Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations.
Conclusion
Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.
The aims of this study were to evaluate the fluorine depth profiles of pure titanium (Ti), stainless steel (SUS), and polymethyl methacrylate (PMMA) modified by plasma-based fluorine ion implantation and the effects of fluorine ion implantation on contact angle, fluoride ion release, and S. mutans adhesion. Fluorine-based gases used were Ar+F2 and CF4. By means of SIMS, it was found that the peak count of PMMA was the lowest while that of Ti was the highest. Then, up to one minute after Ar sputtering, the presence of fluorine and chromic fluoride could be detected by XPS in the surface and subsurface layer. As for the effects of using CF4 gas for fluorine ion implantation into SUS substrate, the results were: contact angle was significantly increased; no fluoride ion release was detected; antibacterial activity was significantly increased while initial adhesion was decreased. These findings thus indicated that plasma-based fluorine ion implantation into SUS with CF4 gas provided surface antibacterial activity which was useful in inhibiting bacterial adhesion. 相似文献
Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs]) are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA) on odontogenic differentiation of SCAPs in vitro and in vivo.
Methods
SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice.
Results
ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs.
Conclusions
These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase–AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration. 相似文献
PURPOSE: It is unclear whether surgical factors can affect the upper lip sensitivity. The aim of this study was to assess the factors that can affect the recovery period of hypoaesthesia of the upper lip after Le Fort I osteotomy, using trigeminal somatosensory evoked potential (TSEP) objectively. PATIENTS AND METHODS: Twenty-nine patients with mandibular prognathism underwent Le Fort I osteotomy with and without artificial pterygoid plate fracture. Trigeminal nerve hypoaesthesia at the region of the upper lip was assessed bilaterally by the TSEP method. The distance between the infraorbital foramen and the osteotomy line (IO) or the nearest plate/screw position (IP) was measured on three-dimensional computed tomography (CT). The relationship between the recovery period in upper lip hypoaesthesia and surgical factors (these distances, movement amount, pterygoid plate fracture) were analysed statistically. RESULTS: The recovery period in upper lip hypoaesthesia did not significantly correlate with IO, IP and movement amount. There was no significant difference between pterygoid plate fracture group and non-fracture group. CONCLUSION: Temporary hypoaesthesia of upper lip after Le Fort I osteotomy could not be avoided, however, osteotomy line, plate/screw position and pterygoid plate fracture in Le Fort I osteotomy did not affect the recovery period of upper lip hypoaesthesia with TSEP. 相似文献