Tailored dose chemotherapy and the relationship with PK.

我们已经开发并建立了一个新的剂量发现系统，一个个人化的最大可重复剂量（iMRD），适合于鼓励TTP比肿瘤收缩更严重，但通过毒性等级1 marrow depression来确定。我们在每周的21名Metastical Gastic癌症患者中应用了这个系统，作为第二行。我们在第五周确定了iMRD，在每周调整后。我们从60毫克/米^2开始服用紫杉醇，并重复治疗，每次增加或减少10毫克/米^2，如果毒性低于1级或更高，请注意。Moreover，我们研究了11名患者的iMRD和AUC之间的相关性，浓度为60毫克/平方米。每周吉西他滨的iMRD为40毫克/米^2在1个病人中， 50毫克/米^2在6个病人中， 60毫克/米^2在6个病人中， 70毫克/米^2在4个病人中，80毫克/米^2在1个病人中表现出明显的差异。2名患者中的3级marrow depression不饱和（9.5%）在这21名患者中， 5名（23.8%）、12名（57.2%）和4名（19.0%）患者展示了PR、SD和PD。TTP的中位数和存活时间分别为5.0个月和9.5个月，值得注意。患者iMRD的AUC值小于50毫克/米^2 （n=3）、50毫克/米^2或60毫克/米^2（n=4）、大于60毫克/米^2（n=3）分别为4133、3721和2057纳克/毫升 * 小时。iMRD和AUC之间存在反向关联。这些结果建议说，iMRD是一种简单的方法，可以确定一个个人用于化疗的尾药，也可以是一种对患者使用这种非正常癌症（如Metastatic Stomach Cancer）的最佳剂量，并且可以由AUC预测开始剂量。

We developed and established a new dose-finding system, the individualized maximum repeatable dose (iMRD), suitable to induce prolonged TTP rather than tumor shrinkage, which is determined by toxicity grade 1 marrow depression. We applied this system in weekly paclitaxel therapy for・21 metastatic gastric cancer patients as second line. We determined the iMRD at the 5th week, after weekly dose adjustments. We started at 60 mg/m^2 of paclitaxel and repeated the treatment with an increase or a decrease of 10 mg/m^2 each week, if toxicity was 0 or more than grade 1, respectively. Moreover, we studied the correlation between iMRD and AUC at 60 mg/m2 of paclitaxel in 11 patients. The iMRD of weekly gemcitabine was 40 mg/m^2 in 1 patient, 50 mg/m^2 in 6 patients, 60 mg/m^2 in 6 patients, 70 mg/m^2 in 4 patients, and 80 mg/m^2 in 1 patient, demonstrating significant differences among individual patients. Grade 3 marrow depression occurred in 2 patients (9.5%). Of these 21 patients, 5 (23.8%), 12 (57.2%) and 4 (19.0%) patients showed PR, SD and PD, respectively. The median of TTP and survival was 5.0 months and 9.5 months, respectively. Means of AUC of the patients whose iMRD were less than 50 mg/m^2 (n=3), 50 mg/m^2 or 60 mg/m^2(n=4), more than 60 mg/m^2(n=3) were 4133, 3721, and 2057 ng/ml*hr, respectively. There were reverse correlation between iMRD and AUC. These results suggest that iMRD is a simple method to determine an individual's tailored dose for chemotherapy and could be the optimal dose for patients with non-curable cancers such as metastatic stomach cancer, and could be predicted by AUC of the starting dose.