Pilot study of PALA and 5-FU in patients with advanced cancer.
Pilot study of PALA and 5-FU in patients with advanced cancer.
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PALA 和 5-FU 在晚期癌症患者中的初步研究。
DOI：
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发表时间：
1982
期刊：
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通讯作者：
C. Moertel
中科院分区：
文献类型：
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作者：
M. O’connell;G. Powis;J. Rubin;C. Moertel
在21例晚期实体瘤患者中进行了一项初步研究，以确定以5天为周期给予PALA和5-FU的适当剂量水平，以产生确定但可耐受的临床毒性。虽然观察到皮炎、腹泻、白细胞减少和血小板减少，但口腔炎是剂量限制的副作用。进一步临床试验的推荐初始剂量水平为每日625mg /m2 PALA x 5和每日250- 300mg /m2 5- fu x 5，每4周重复一次疗程。还进行了研究，以确定在PALA治疗后5-FU进入细胞RNA的预期增加的时间过程。在小鼠P388白血病中，PALA可使氚化5-FU掺入率提高70%，效果在1小时内达到最大，并可维持25小时。无法证明接受PALA和5-FU联合化疗的患者对正常人白细胞RNA的氚化5-FU摄取增加，可能是因为RNA合成率较低。
A pilot study was carried out among 21 patients with advanced solid tumors to establish appropriate dose levels of PALA and 5-FU given on a 5-day schedule to produce definite but tolerable clinical toxicity. While dermatitis, diarrhea, leukopenia, and thrombocytopenia were observed, stomatitis was the dose-limiting side effect. The recommended initial dose levels for further clinical trials are 625 mg/m2 of PALA daily x 5 and 250-300 mg/m2 of 5-FU daily x 5, with courses repeated at 4-week intervals. Studies were also conducted to establish the time course of anticipated increased incorporation of 5-FU into cellular RNA following treatment with PALA. In murine P388 leukemia, PALA increased tritiated 5-FU incorporation by as much as 70%, the effect being maximal within 1 hour and maintained up to 25 hours. It was not possible to demonstrate increased tritiated 5-FU uptake into normal human leukocyte RNA from patients receiving combination chemotherapy with PALA and 5-FU, perhaps because of low rates of RNA synthesis.