Wadler S, Gleissner B, Hilgenfeld R U, Thiel E, Haynes H, Kaleya R, Rozenblit A, Kreuser E D
Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Eur J Cancer. 1996 Jun;32A(7):1254-6. doi: 10.1016/0959-8049(96)00035-4.
The aspartate transcarbamoylase inhibitor, N-(phosphonacetyl)-L-aspartate (PALA), synergistically enhanced the cytotoxicity of a combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN) against human colon cancer cell 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.
天冬氨酸转氨甲酰酶抑制剂N-（膦酰乙酰基）-L-天冬氨酸（PALA）在体外可协同增强5-氟尿嘧啶（5-FU）与α干扰素（IFN）联合用药对人结肠癌细胞系的细胞毒性。为了在临床环境中测试这种联合用药的疗效，对局部晚期或晚期胃癌患者采用PALA、5-FU和IFN联合用药（PFI）进行治疗。患者需经活检证实疾病超出手术切除范围、有可测量病灶、未曾接受过化疗、骨髓、肾脏和肝脏功能正常、能够完全自主活动且已签署知情同意书。给药方案如下：PALA，250mg/m²，静脉输注15分钟，第1、15、22、29天给药，之后每周给药一次；5-FU，750mg/m²，从第2天开始持续静脉输注，每日一次，共5天，然后在第16、23和30天给予750mg/m²，之后每周给药一次；IFN，从第2天开始，每周皮下注射3次，每次9MU。共有22例患者入组。主要毒性为疲劳及相关神经毒性，胃肠道和血液学毒性可接受。有1例完全缓解者（5%）和3例部分缓解者（14%）；其中2例缓解持续时间超过3年。尽管临床活性有限，但其他晚期胃癌治疗方案，如FAMTX和ELF，似乎具有更高的活性且毒性相当。
