Pharmacokinetics of Weekly Paclitaxel and Feasibility of Dexamethasone Taper in Japanese Patients with Advanced Non–small Cell Lung Cancer

AbstractPurposeWeekly paclitaxel combined with a platinum-based agent has been advocated as an alternative regimen for patients with advanced non–small cell lung cancer (NSCLC). Limited studies exist on the tolerability of weekly paclitaxel in Japanese patients with advanced NSCLC. Furthermore, the feasibility of dexamethasone taper in the premedication regimen for weekly paclitaxel has not been examined in these patients. To address this issue, we assessed the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of weekly paclitaxel in Japanese patients with advanced NSCLC in a dose-escalation Phase I trial and examined the feasibility of dexamethasone taper in these patients.MethodsWeekly 1-hour infusions of paclitaxel were administered at doses of 80 to 120 mg/m2 (dose escalation of 20 mg/m2). The 7-week treatment cycle consisted of 6 infusions followed by a 2-week treatment interval. Pharmacokinetics were assessed during the first cycle. Dexamethasone was commenced at 16 mg and doses were successively halved if hypersensitivity reactions were absent.FindingsA total of 15 patients with either Stage IIIB or IV NSCLC were enrolled. Although no dose-limiting toxicity was observed at 120 mg/m2, 4 of 6 patients with peripheral neuropathy required discontinuation of treatment. The maximum accepted dose and the recommended dose were 120 and 100 mg/m2, respectively. No grade ≥3 adverse events were observed at 100 mg/m2. The maximum drug concentration and AUC correlated with dose escalation. The pharmacokinetic parameters after the first and sixth infusions were similar, indicating that repeated administration of paclitaxel did not result in drug accumulation or affect its pharmacokinetic profile. Partial response was observed in 3 of 15 patients. Plasma adrenocorticotropic hormone and cortisol levels decreased during treatment but approached baseline levels after a dexamethasone-free interval.ImplicationsWeekly paclitaxel at 100 mg/m2 given as a 1-hour infusion for 6 weeks followed by a 2-week treatment interval was well tolerated by Japanese patients with advanced NSCLC. Dexamethasone taper was feasible in these patients, and no clear trend in plasma adrenocorticotropic hormone or cortisol levels was observed

Histologic Transformation from Follicular Lymphoma to Diffuse Large B-cell Lymphoma Detected during Colonoscopy

A 77-year-old Japanese woman who had been treated for follicular lymphoma for 8 years developed abdominal pain and intra-abdominal lymphadenopathies. Colonoscopy revealed an elevated lesion in the rectum, which presented as two humps with erosions. A diagnosis of histologic transformation of follicular lymphoma to diffuse large B-cell lymphoma was made by endoscopic biopsy. This case underscores the importance of endoscopy examinations and biopsy of newly emerged gastrointestinal lesions for the prompt diagnosis of histologic transformation, since salvage chemotherapy must be initiated quickly in such cases

Datura属植物組織培養におけるアルカロイド生成に関する研究

京都大学0048新制・論文博士薬学博士乙第2996号論薬博第157号新制||薬||74(附属図書館)4770UT51-61-I228(主査)教授 木島 正夫, 教授 井上 博之, 教授 藤田 栄一学位規則第5条第2項該当Kyoto UniversityDA