Blumberg A L, Nelson D F, Gramkowski M, Glover D, Glick J H, Yuhas J M, Kligerman M M
Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):561-3. doi: 10.1016/0360-3016(82)90684-8.
The radioprotector with clinical potential, S-2-(3 aminopropylamino)-ethylphosphorothioic acid (WR-2721) is undergoing two Phase I trials. The objectives of these trials are 1) to determine the maximum tolerated dose (MTD) of WR-2721 in a single dose and 2) to determine the highest dose of WR-2721 that can be tolerated daily in the greatest number of fractions per week. A total of 65 patients have been treated. The single maximum tolerated dose has not yet been reached, though 740 mg/m2 is well tolerated. A single dose of 910 mg/m2 has been successfully administered to one patient. The multiple dose MTD is at an early stage with patients currently receiving 170 mg/m2 four times a week. Among the toxicities noted in both trials are hypotension, hypertension, emesis and somnolence. In addition, in the multiple dose trial there have been three patients who have had allergic reactions including one which was life-threatening. Phase II studies are planned and will begin when the maximum tolerated dose is established from each Phase I trial.
具有临床应用潜力的辐射防护剂S-2-(3-氨丙基氨基)乙硫代磷酸（WR-2721）正在进行两项I期试验。这些试验的目的是：1）确定WR-2721的单剂量最大耐受剂量（MTD）；2）确定每周能耐受最大次数分次给药的WR-2721最高剂量。共有65名患者接受了治疗。虽然740mg/m²耐受性良好，但尚未达到单剂量最大耐受剂量。一名患者成功接受了910mg/m²的单剂量给药。多剂量MTD尚处于早期阶段，目前患者每周接受4次170mg/m²的给药。两项试验中观察到的毒性反应包括低血压、高血压、呕吐和嗜睡。此外，在多剂量试验中，有3名患者出现过敏反应，其中1例危及生命。计划进行II期研究，待每项I期试验确定最大耐受剂量后开始。
