当前位置： SCI文献检索 > CANCER CHEMOTHERAPY AND PHARMACOLOGY期刊下所有文献 > Phase I trial of combination therapy of cancer with N-phosphonacetyl-L-aspartic acid and dipyridamole.

Phase I trial of combination therapy of cancer with N-phosphonacetyl-L-aspartic acid and dipyridamole.

Abstract：

:While N-phosphonacetyl-L-aspartic acid (PALA), an inhibitor of de novo pyrimidine biosynthesis, demonstrated a unique spectrum of activity during preclinical drug evaluation, multiple clinical trials have shown it to possess minimal clinical activity. One explanation for the disappointing results is the possibility that tumor cells are able to utilize circulating uridine in the synthesis of pyrimidines (salvage pathway). Dipyridamole, an inhibitor of nucleoside transport, has been demonstrated experimentally to potentiate the cytotoxicity of PALA significantly. In addition, this agent has a long safety record when used clinically in man. A phase I trial of this two-drug combination was therefore conducted, with a fixed oral dose of dipyridamole (50 mg/m2 every 6 h) and an escalating i.v. dose of PALA administered every 3 weeks. The dose-limiting toxicity with this schedule was diarrhea and abdominal cramping pain at a PALA dose of 3900-4200 mg/m2. Among the 65 patients participating in this trial 4 objective responses (2 partial, 2 minimal) were observed. Because of the potential for unique clinical synergy between PALA and dipyridamole further investigation should be considered.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Markman M,Chan TC,Cleary S,Howell SB

doi

10.1007/BF00296262

subject

Has Abstract

pub_date

1987-01-01 00:00:00

pages

80-3

issue

1

eissn

0344-5704

issn

1432-0843

journal_volume

19

pub_type

杂志文章

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