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- W2005905993 abstract "Background. 5-Fluorouracil (5-FU) has modest activity as a single agent in a number of human adenocarcinomas. The technique of biochemical modulation has been used preclinically to increase the activity of 5-FU. Methods. With doses based on a Phase I study, the authors performed a Phase II trial in patients with advanced metastatic adenocarcinoma of an unknown primary site using N-phosphonacetyl-I-aspartate (PALA), methotrexate (MTX), 5-FU, and leucovorin. In some patients, 5-phosphoriosyl-l-pyrophosphate (PRPP) and uridine triphosphate (UTP) metabolite pools were assayed before and after PALA and MTX to assess metabolite pool shifts. Results. Twenty-one patients were treated in this Phase I1 trial. Toxicity was tolerable. Biopsy specimens of tumor tissue showed increases in PRPP and decreases in UTP levels in two of three and three of four patients, respectively. However, only one objective response was seen, which is not different from that expected with 5-FU alone. Conclusions. Expected PRPP and UTP metabolite pool shifts were seen when biochemical modulation was performed with these drugs according to this schedule. Because toxicity was mild, more intense dose schedules of 5-FU are planned for future studies. Cancer 1992; 70:1988–1992." @default.
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- W2005905993 date "1992-10-01" @default.
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- W2005905993 title "A phase II trial of biochemical modulation using N- phosphonacetyl-L-aspartate, high-dose methotrexate, high-dose 5-fluorouracil, and leucovorin in patients with adenocarcinoma of unknown primary site" @default.
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- W2005905993 doi "https://doi.org/10.1002/1097-0142(19921001)70:7<1988::aid-cncr2820700730>3.0.co;2-k" @default.
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