The aspartate transcarbamoylase inhibitor, N-(phosphonacetyl)-L- aspartate (PALA), synergistically enhanced the cytotoxicity of a combination of 5-fluorouracil (5-FU) and interferon-α (IFN) against human colon cancer ceil lines in vitro. To test the efficacy of this combination in the clinical setting, patients with locally advanced or advanced gastric carcinoma were treated with the combination of PALA, 5-FU and IFN (PFI). Patients were required to have biopsy-proven disease beyond the scope of surgical resection, measurable disease, no prior chemotherapy, adequate bone marrow, renal and hepatic function, to be fully ambulatory and to have given informed consent. Drug was administered as follows: PALA, 250 mg/m2, 15 min i.v. infusion, days 1, 15, 22, 29, and then weekly; 5-FU, 750 mg/m2 daily x 5 as a continuous i.v. infusion beginning day 2, then at 750 mg/m2 days 16, 23 and 30, then weekly; IFN, 9 MU subcutaneously three times per week beginning day 2. There were 22 patients enrolled. The major toxicities were fatigue and associated neurotoxicity, with acceptable gastrointestinal and haematological toxicities. There was one complete responder (5%) and 3 partial responders (14%); two of these responses were durable (> 3 years). Despite this modest clinical activity, other regimens for advanced gastric cancer such as FAMTX and ELF appear to have greater activity with comparable toxicity.
- N-(phosphonacetyl)-L-aspartate (PALA)
- biochemical modulation
- gastric cancer
ASJC Scopus subject areas
- Cancer Research