A pilot study of individualized maximum repeatable dose (iMRD), a new dose finding system, of weekly gemcitabine for patients with metastatic pancreas cancer
A pilot study of individualized maximum repeatable dose (iMRD), a new dose finding system, of weekly gemcitabine for patients with metastatic pancreas cancer
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DOI：
10.1097/01.mpa.0000153335.73352.c7
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发表时间：
2005-04-01
期刊：
影响因子：
2.9
通讯作者：
Nishioka, K
中科院分区：
文献类型：
--
作者：
Takahashi, Y;Mai, M;Nishioka, K
目的：我们开发和建立了一个新的剂量发现系统，个性化的最大可重复剂量（iMRD），适合诱导延长TTP而不是肿瘤shortcenter.Methods：我们应用这个系统在每周吉西他滨治疗18例转移性胰腺癌患者。在每周剂量调整后，我们在第5周确定iMRD。我们从500 mg/m2开始（1/2最大耐受剂量）的吉西他滨，并重复治疗，增加或减少100 mg/m2，每周，如果毒性分别为0或大于1级。吉西他滨每周一次的iMRD为300 mg/m2（2例患者）、400 mg/m2（3例患者）、500 mg/m2（5例患者）、600 mg/m2（6例患者）和700 mg/m2（2例患者），显示了个体患者之间的显著差异。仅1例患者（5.6%）发生3级骨髓抑制。在这18例患者中，3例（16.7%）、13例（72.2%）和2例（11.1%）患者分别显示部分缓解、疾病稳定和疾病进展。中位疾病进展时间和生存期分别为4.5和9.5个月。胰腺癌的肿瘤标志物CA 19 -9降低50%以上的患者与低分化的胰腺癌患者相比，（500 mg/m2或更低）及更高（600 mg/m2或更高）iMRD。结论：这些结果表明，iMRD是确定个人定制化疗剂量的简单方法，并且可能是不可治愈癌症患者的最佳剂量例如转移性胰腺癌。
Objectives: We developed and established a new dose-finding system, the individualized maximum repeatable dose (iMRD), suitable to induce prolonged TTP rather than tumor shrinkage.Methods: We applied this system in weekly gemcitabine therapy for 18 metastatic pancreas cancer patients. We determined the iMRD at the 5th week, after weekly dose adjustments. We started at 500 mg/m(2) (1/2 maximum tolerated dose) of gemcitabine and repeated the treatment with an increase or a decrease of 100 mg/m(2) each week, if toxicity was 0 or more than grade 1, respectively.Results: The iMRD of weekly gemcitabine was 300 mg/m2 in 2 patients, 400 mg/m(2) in 3 patients, 500 mg/m(2) in 5 patients, 600 mg/m(2) in 6 patients, and 700 mg/m(2) in 2 patients, demonstrating significant differences among individual patients. Grade 3 marrow depression occurred in only 1 patient (5.6%). Of these 18 patients, 3 (16.7%), 13 (72.2%) and 2 (11.1%) patients showed partial response, stable disease, and progressive disease, respectively. The median of times to progressive disease and survival were 4.5 and 9.5 months, respectively. There were no significant differences in 1-year survival time and more than 50% reduction rate of serum CA19-9, a tumor marker for pancreatic cancer, between patients with lower (500 mg/m(2) or less) and higher (600 mg/m(2) or more) iMRD.Conclusion: 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 noncurable cancers such as metastatic pancreas cancer.