Turrisi A T, Glover D J, Hurwitz S, Glick J, Norfleet A L, Weiler C, Yuhas J M, Kligerman M M
Cancer Treat Rep. 1986 Dec;70(12):1389-93.
Two hundred one patients were entered in a single-dose phase I trial of WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid]. Major toxic effects included emesis and hypotension. The observed minor toxic effects were somnolence and sneezing. Two infusion schedules were tested: long-infusion time, which fixed the rate, but varied total time; and short-infusion time, which varied the rate, but fixed the time to 15 minutes. Emesis was significantly influenced by infusion time; the long schedule caused a 57% incidence whereas the short schedule caused only a 28% incidence. Within the long-infusion group, higher-dose patients and women were more likely to vomit. Although only 15% of the entire group had hypotension, the long-infusion schedule had a hypotension incidence of 23%; the short schedule had an incidence of only 3% (P less than 0.0005). Within the long-infusion group, dose and tumor site significantly influenced the incidence of hypotension. No factors were associated with these toxic effects in the short-infusion schedule. However, certain toxic effects were too infrequent to detect significant differences. For future trials we recommend 740 mg/m2 infused in 15 minutes. With this schedule, vomiting was seen in 25% of infusions and hypotension was seen in only one of 68 infusions. To date, no delayed toxic effects have been detected in any organ system, and the trial resulted in no toxic deaths.
201名患者参与了WR-2721[ S-2-(3-氨丙基氨基)乙硫代磷酸]的单剂量I期试验。主要毒性作用包括呕吐和低血压。观察到的次要毒性作用为嗜睡和打喷嚏。测试了两种输注方案：长时间输注方案，固定速率但总时间可变；短时间输注方案，速率可变但时间固定为15分钟。呕吐受输注时间的显著影响；长时间输注方案的发生率为57%，而短时间输注方案仅为28%。在长时间输注组中，高剂量患者和女性更易呕吐。尽管整个组中只有15%的患者出现低血压，但长时间输注方案的低血压发生率为23%；短时间输注方案的发生率仅为3%（P<0.0005）。在长时间输注组中，剂量和肿瘤部位显著影响低血压的发生率。短时间输注方案中没有因素与这些毒性作用相关。然而，某些毒性作用发生频率过低，无法检测到显著差异。对于未来试验，我们建议在15分钟内输注740mg/m²。采用该方案，25%的输注出现呕吐，68次输注中仅1次出现低血压。迄今为止，在任何器官系统中均未检测到延迟毒性作用，且该试验未导致毒性死亡。
