NSC 224131 (PALA)

05/01/1992 - "Two previous studies of patients with colorectal carcinoma documented complete response (CR) and partial response (PR) rates of 40% and 43% using weekly low-dose PALA followed by a 24-hour FU infusion. "
02/01/1980 - "PALA appears inactive in patients with metastatic colorectal carcinoma in the dose and schedule used in this study."
10/01/1997 - "PALA/MTX/5-FU in this dose and schedule is active in patients with colorectal cancer. "
01/01/1994 - "Although PALA (250 mg/m2) can be combined with full dosage 5-FU/FA, the combination has poor activity in colorectal cancer."
05/01/1992 - "Forty-five patients without prior chemotherapy who had advanced colorectal carcinoma were treated with PALA 250 mg/m2 followed 24 hours later by bolus FU at three dose levels, 600, 700, 800 mg/m2, repeated weekly for 6 weeks followed by a 2-week break. "

08/01/1976 - "Lewis lung tumors had reached about 500 mg, PALA neither cured the mice nor produced significant tumor regression. "
02/01/1982 - "PALA equivalents were poorly taken up by mouse tumors and tissues, except kidney, bone, and to a lesser extent, skin and lung, and were rapidly and extensively cleared from all except bone. "
01/01/2015 - "From 1994 to 2004, in the Cancer Institute Hospital, 502 patients who were surgically treated with systematic PLA and PALA were enrolled in this study. "
01/01/1980 - "Delineation of the single-agent activity of PALA in human cancer must still await results of recently activated trials."
03/15/2005 - "The best hCA IV inhibitors were PALA (79 nM) and PPA (5.4 microM), whereas the other compounds showed K(I)s in the range of 0.31-5.34 mM. The mitochondrial isozyme was weakly inhibited by all these compounds (K(I)s in the range of 0.09-41.7 mM), similarly to the transmembrane, tumor-associated isozyme (K(I)s in the range of 0.86-2.25 mM). "

03/01/1981 - "Phase II study of PALA in advanced large bowel carcinoma."
04/01/1993 - "Antitumor activity of the weekly intravenous push schedule of 5-fluoro-2'-deoxyuridine +/- N-phosphonacetyl-L-aspartate in mice bearing advanced colon carcinoma 26."
08/01/1985 - "Evidence presented here supports the ability of DP to potentiate PALA activity against a human ovarian carcinoma cell line. "
08/01/1985 - "In a human ovarian carcinoma cell line (2008), DP increased the activity of PALA by 1 to 2 logs in growth rate and clonogenic assays while exhibiting no cytotoxicity of its own. "
12/01/1984 - "Thirty-six patients with advanced carcinoma of the cervix received PALA at a dosage of 5 gm/m2 every three weeks. "

10/01/1982 - "Differential effect of N-(phosphonacetyl)-L-aspartate on 1-beta-D-arabinofuranosylcytosine metabolism and cytotoxicity in human leukemia and normal bone marrow progenitors."
02/01/1996 - "Ara-C cytotoxicity to leukemic blast cells from 11 untreated patients with different types of leukemia was only modulated to a small extent by high PALA concentrations in only two cases. "
04/01/1985 - "At the clinically relevant concentration of 1 microM, dipyridamole increased the cytotoxicity of PALA against a melanoma, a colon carcinoma, a promyelocytic leukemia (HL-60), and normal marrow (CFU-GM) in clonogenic assays. "
04/01/1993 - "At the maximum tolerated doses, the antitumor activity in mice bearing advanced colon carcinoma can be summarized as follows: (a) FdUrd is significantly more active than FUra; (b) for both drugs the weekly for 3 weeks i.v. push schedule is superior to the c.i. or i.v. push daily for 4 days schedules; (c) pretreatment with PALA enhances the antitumor activity of FdUrd and FUra and resulted in 95 and 13% complete responses, respectively; (d) long-term survivors with FUra could only be achieved in the presence of PALA; in mice bearing leukemia 1210 cells, FdUrd or FUra with or without PALA exhibited no significant antitumor activity when PALA was administered in a single dose 24 h prior to fluoropyrimidine treatment; and (e) in C-26 and L1210, PALA reduced the pools of CTP and UTP equally, to about 10% of controls with significant difference in their rates of recovery."
08/01/1976 - "PALA, unlike other antimetabolites, was less effective against ascitic leukemias than against two solid tumors, B16 melanoma and Lewis lung carcinoma. "

11/01/2001 - "Twenty-seven patients with gastrointestinal tract adenocarcinomas were treated with PALA 1266 mg/m2/15 min followed by a 72-hour infusion of FUra and LV (1750 & 500 mg/m2/day) given by fixed- or variable-rate (peak at 4:00 A.M.). "
03/15/1996 - "A 72-h exposure to PALA (> or = 25 microM) delayed the growth of human ovarian adenocarcinoma BG-1 cells by 40% compared to that of the untreated control cells. "
01/01/1996 - "PALA and 5-FU is inactive against gastric adenocarcinoma at the doses and schedule used in this trial."
01/01/1996 - "In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an initial period of 8 weeks. "
10/01/1994 - "This Phase I study was undertaken to determine the feasibility and evaluate the qualitative and quantitative toxicities of PALA and escalating doses of 5-FU administered concomitantly with radiation therapy in patients with locally advanced nonmetastatic pancreatic adenocarcinoma. "