Abstract |
N-(phosphonacetyl)- L-aspartic acid ( PALA) inhibits the enzyme L-aspartic acid transcarbamoylase (ATCase) which is important in de novo pyrimidine synthesis. Low dosages of PALA modulate the in vitro activity of 5-fluorouracil (5-FU) and PALA (250 mg/m2) inhibits pyrimidine synthesis in patients. PALA (250 mg/m2 day 1) was combined with an established 5-FU/ folinic acid (FA) regimen [FA (200 mg/m2 over 2 h days 2 + 3) and bolus and 22 h infusional 5-FU (300-500 mg/m2 days 2 + 3)] without the need for dose reduction of 5-FU or FA. 35 patients were entered. Treatment was well tolerated; 4/27 patients experienced > or = ECOG grade 3 toxicity at full 5-FU dosage (500 mg/m2 bolus/infusion). However, the response rate in 33 evaluable patients was only 6.1% [95% confidence intervals (C.I.) 0.2-21.8%]. Median response duration was short (4 months, 95% C.I. 3-6 months) and overall median survival was 10 months (95% C.I. 7-16 months). Although PALA (250 mg/m2) can be combined with full dosage 5-FU/FA, the combination has poor activity in colorectal cancer.
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Authors | D I Jodrell, W Oster, D J Kerr, P A Canney, H Yosef, W P Steward, S B Kaye, J Cassidy |
Journal | European journal of cancer (Oxford, England : 1990)
(Eur J Cancer)
Vol. 30A
Issue 7
Pg. 950-5
( 1994)
ISSN: 0959-8049 [Print] England |
PMID | 7946590
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
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Chemical References |
- Aspartic Acid
- sparfosic acid
- Phosphonoacetic Acid
- Leucovorin
- Fluorouracil
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Topics |
- Adolescent
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Aspartic Acid
(administration & dosage, adverse effects, analogs & derivatives)
- Colonic Neoplasms
(drug therapy, mortality)
- Disease Progression
- Dose-Response Relationship, Drug
- Female
- Fluorouracil
(administration & dosage, adverse effects)
- Humans
- Leucovorin
(administration & dosage, adverse effects)
- Male
- Middle Aged
- Phosphonoacetic Acid
(administration & dosage, adverse effects, analogs & derivatives)
- Rectal Neoplasms
(drug therapy, mortality)
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