Kris M G, Gralla R J, Clark R A, Tyson L B
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
J Clin Oncol. 1988 Apr;6(4):659-62. doi: 10.1200/JCO.1988.6.4.659.
GR-C507/75 (GR38032F) antagonizes the 5-HT3 (serotonin) receptor and prevents cisplatin-induced emesis in animals. In this dose-ranging trial, 44 patients with cancer receiving chemotherapy known to produce nausea and vomiting (including cisplatin, cyclophosphamide, and doxorubicin) received three intravenous (IV) infusions of GR-C507/75 every two hours beginning 30 minutes before chemotherapy. Ten dosage levels were explored, ranging from 0.04 mg/kg to 0.35 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, headache, transient elevations of SGOT or alanine aminotransferase (ALT), and dry mouth. No akathisia or acute dystonic reactions were observed. Antiemetic effects were seen in patients receiving cisplatin at 120 mg/m2. GR-C507/75 can be safely administered on this schedule at IV dosages up to 0.35 mg/kg in patients receiving chemotherapy. Further studies of this agent at higher dosages and by different schedules are appropriate.
GR - C507/75（GR38032F）可拮抗5 - HT3（血清素）受体，并能预防动物顺铂诱导的呕吐。在这项剂量范围试验中，44例接受已知会引起恶心和呕吐的化疗（包括顺铂、环磷酰胺和阿霉素）的癌症患者，在化疗前30分钟开始，每两小时静脉输注三次GR - C507/75。研究了十个剂量水平，三次输注中每次的剂量范围为0.04 mg/kg至0.35 mg/kg。毒性较轻，包括镇静、头晕、头痛、血清谷草转氨酶（SGOT）或谷丙转氨酶（ALT）短暂升高以及口干。未观察到静坐不能或急性肌张力障碍反应。接受120 mg/m²顺铂治疗的患者出现了止吐作用。对于接受化疗的患者，按此给药方案静脉剂量高达0.35 mg/kg时，GR - C507/75可安全给药。对该药物进行更高剂量和不同给药方案的进一步研究是合适的。
