Bleiberg H, Piccart M, Lips S, Panzer J M, N'Koua Mbon J B
Service de Médecine Interne et Laboratoire d'Investigation Clinique H.J. Tagnon, Unité de Gastroentérologie, Brussels, Belgium.
Ann Oncol. 1992 Feb;3(2):141-3. doi: 10.1093/oxfordjournals.annonc.a058130.
Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.
氯波必利是一种新型苯甲酰胺衍生物，与该类其他成员一样，具有抗多巴胺能活性。在动物实验中，在无高催乳素血症和锥体外系症状相关副作用的剂量下，其治疗指数优于甲氧氯普胺。本研究旨在确定经组织学证实的晚期癌症患者接受顺铂剂量大于50mg/m²治疗时的最大耐受剂量（MTD）。大多数患者曾接受过预处理且对标准止吐药无效。在一组6名患者中，氯波必利起始剂量为0.10mg/kg，并在每个剂量水平增加0.2mg。总共纳入了30名患者。副作用包括嗜睡、腹泻和锥体外系样症状。后者在几乎所有剂量水平下均有发生，占周期数的14%，并限制了研究的继续进行。该组患者的疗效令人鼓舞，但考虑到锥体外系症状的发生率，不建议进一步增加剂量，应研究较低无毒水平下的疗效。
