PHASE-II TRIAL OF N-(PHOSPHONACETYL)-L-ASPARTATE (PALA), 5-FLUOROURACIL AND RECOMBINANT INTERFERON-ALPHA-2B IN PATIENTS WITH ADVANCED GASTRIC-CARCINOMA

The aspartate transcarbamoylase inhibitor, N-(phosphonacetyl)-L-aspart ate (PALA), synergistically enhanced the cytotoxicity of a combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN) against human col on cancer cell lines in vitro. To test the efficacy of this combinatio n 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 chemoth erapy, adequate bone marrow, renal and hepatic function, to be fully a mbulatory and to have given informed consent. Drug was administered as follows: PALA, 250 mg/m(2), 15 min i.v. infusion, days 1, 15, 22, 29, and then weekly; 5-FU, 750 mg/m(2) daily x 5 as a continuous i.v. inf usion beginning day 2, then at 750 mg/m(2) days 16, 23 and 30 then wee kly; IFN, 9 MU subcutaneously three times per week beginning day 2. Th ere were 22 patients enrolled. The major toxicities were fatigue and a ssociated neurotoxicity, with acceptable gastrointestinal and haematol ogical toxicities. There was one complete responder (5%) and 3 partial responders (14%); two of these responses were durable (> 3 years). De spite this modest clinical activity, other regimens for advanced gastr ic cancer such as FAMTX and ELF appear to have greater activity with c omparable toxicity. Copyright (C) 1996 Elsevier Science Ltd.