Phase I trials of WR2721 in combination with radiation therapy and with the alkylating agents cyclophosphamide and cis-platinum.
Phase I trials of WR2721 in combination with radiation therapy and with the alkylating agents cyclophosphamide and cis-platinum.
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WR2721 联合放射治疗以及烷化剂环磷酰胺和顺铂的 I 期试验。
DOI：
10.1016/0360-3016(81)90259-5
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
R. Goodman
中科院分区：
文献类型：
--
作者：
M. Kligerman;A. Blumberg;J. Glick;D. Nelson;D. Glover;J. Yuhas;H. Amols;R. Goodman
放射防护剂S-2-（S-氨丙基氨基）乙基硫代磷酸（WR 2721）的三个I期试验已访问了60名患者。研究1旨在确定在姑息治疗中常规使用的剂量的单次放射治疗前15至30分钟单次剂量的保护剂的最大耐受剂量（MTD）。研究2计划确定姑息性放疗期间3周内最多15次每日剂量药物的MTD。此外，多次给药研究将确定姑息性照射前的MTD，每周少于5次。研究3使用研究I中确定的现有单次给药MTD作为环磷酰胺顺式铂前15 - 30分钟的治疗。中毒症状包括呕吐、低血压、高血压、嗜睡和打喷嚏。只有严重的低血压发作，被认为是特异性的，和1例中度至重度呕吐。41例患者入组研究1，剂量达到600 mg/m2。步骤是继续进行到740 kg/m2的计划最高水平。在多次给药研究中的五名患者中，一名患者在3周内以mg/m2的水平给予WR 2721 15个分数而没有毒性。14名患者进入烷基化剂研究。使用剂量为450 mg/m2，环磷酰胺水平为500 mg/m2。然而，两名接受450 mg/m2的WR 2721和120 mg/m2的顺铂的患者显示出中度的血清肌酐，两者均恢复正常。
THREE PHASE I TRIALS of the radio protector S-2-(s-aminopropylamino) ethlyphosphorothioic acid (WR2721) have accessed 60 patients. Study 1 is devised to determine the maximum tolerated dose (MTD) of a single dose of the protector 15 to 30 minutes before a single radiation treatment of a size used routinely in paliative management. Study 2 plans to determine the MTD for up to 15 daily doses of the drug over 3 weeks during palliative radiotherapy. Also, the multiple-dose study will establish the MTD before palliative irradiation for fewer than five fractions a week. Study 3 uses the existing single-dose MTD determined in Study I as treatment 15 to 30 minutes before cyclophosphamide cis-platimum. Toxic symptoms include emesis, hypoension, hypetension, somnolence, and sneezing. Only the serious episode of hypo tension, considered idiosyntrabc, and one instance of moderate to severe vomiting five occurred. Forty-one patients have been entered in study 1 and dose of 600 mg/m 2 has been reached. The step is to proceed to the planed highest level of 740 kg/m 2. Of five patients in the multiple-dose study, one been given without toxicity, WR2721 at the level of mg/m 2 for 15 fractions over 3 weeks. Fourteen patients are accessed to the alkyl ting agent study. Using doses of 450 mg/m 2, a cyclophosphamide level 500 mg/m 2 has been accomplished. However, two three patients who received 450mg/m 2 of WR2721 120 mg/m 2 of cis-platinum have shown moderateof the serum cretonne, both of which returned normal.