Phase I-phase II trial of N-phosphonacetyl-L-aspartic acid given by intravenous infusion and 5-fluorouracil given by bolus injection.
Phase I-phase II trial of N-phosphonacetyl-L-aspartic acid given by intravenous infusion and 5-fluorouracil given by bolus injection.
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N-膦乙酰基-L-天冬氨酸静脉输注和5-氟尿嘧啶推注的I期-II期试验。
DOI：
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发表时间：
1982
期刊：
影响因子：
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通讯作者：
B. Chabner
中科院分区：
文献类型：
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作者：
C. Erlichman;R. Donehower;J. Speyer;R. Klecker;B. Chabner
对30例患者进行了n -乙酰- l-天冬氨酸（PALA）和5-氟尿嘧啶（FUra）的I期临床试验。PALA静脉滴注15分钟，每天1次，连续5天，FUra在第2、3、4、5天静脉滴注。治疗周期每3周重复一次。剂量限制性毒性表现为口腔炎和腹泻。皮肤皮疹也被观察到，但不是剂量限制。未观察到一致的造血或肾毒性。对17例弥散性转移性黑色素瘤和可测量疾病患者的反应进行了评估。我们看到了一个部分反应；然而，这种反应与明显的毒性有关，治疗不能重复。黑色素瘤3例，结肠癌1例，卵巢癌1例，病情稳定。我们的研究结果表明，按照上述方案给予PALA和FUra治疗黑色素瘤的临床活性均小于25% （P < 0.05）。FUra的药代动力学研究显示PALA预处理对血浆中FUra消失没有一致的影响。血浆中FUra的平均消除半线为7.11 +/- 0.84分钟（SEM），与单独FUra的报告没有差异。II期研究的推荐剂量为1000mg PALA/m2/day iv，每天5天，200mg FUra/m2/day iv，第2、3、4和5天。
A phase I clinical trial of N-phosphonacetyl-L-aspartic acid (PALA) and 5-fluorouracil (FUra) was performed on 30 patients. PALA was given as a 15-minute iv infusion once daily for 5 days, and FUra was given as a bolus injection on days 2, 3, 4, and 5. Cycles of treatment were repeated every 3 weeks. Dose-limiting toxicity was manifested by stomatitis and diarrhea. Skin rash was observed also but was not dose limiting. No consistent hematopoietic or renal toxicity was observed. Seventeen patients with disseminated metastatic melanoma and measurable disease were evaluated for response. One partial response was seen; however, the response was associated with significant toxicity, and the treatment could not be repeated. Stable disease was observed in 3 patients with melanoma, 1 patient with colon carcinoma, and 1 patient with ovarian carcinoma. Our findings suggest that the clinical activity of PALA and FUra given according to the above schedule for melanoma is less than 25% (P less than 0.05). Pharmacokinetic studies of FUra revealed no consistent effect of PALA pretreatment on FUra disappearance in plasma. The mean FUra elimination half-line in plasma was 7.11 +/- 0.84 minutes (SEM), which is no different from that reported for FUra alone. The recommended doses on this schedule for phase II studies are 1,000 mg PALA/m2/day iv daily for 5 days and 200 mg FUra/m2/day iv on days 2, 3, 4, and 5.