Raber M N, Adams F, Kavanagh J, Legha S, Dimery I, Krakoff I
Cancer Treat Rep. 1987 Apr;71(4):349-52.
We conducted a phase I trial of caracemide, a new chemotherapeutic agent, which is active in the MX1 (mammary) and CX1 (colon) human tumor xenografts. Using a 5-day bolus schedule, dose-limiting toxicity consisting of burning perioral pain associated with flushing, nasal stuffiness, and excess lacrimation was seen at 650 mg/m2/day. Using a 5-day continuous-infusion schedule, dose-limiting toxicity in the form of changes in affect, lethargy, disorientation, and cognitive dysfunction with electroencephalogram abnormalities was noted at 800 mg/m2/day. The recommended phase II dose levels are 525 mg/m2/day using the 5-day bolus schedule and 650 mg/m2/day using the continuous-infusion schedule. Because of venous pain at the site of infusion, the drug must be delivered via central venous access. The pathophysiology of both the peripheral and central side effects of caracemide may be related to increased cholinergic activity.
我们开展了一项关于新化疗药物卡醋胺的I期试验，该药物对MX1（乳腺）和CX1（结肠）人肿瘤异种移植模型具有活性。采用5天推注给药方案时，在剂量为650 mg/m²/天时出现了剂量限制性毒性，表现为伴有面部潮红、鼻塞和流泪过多的口周灼痛。采用5天持续静脉输注给药方案时，在剂量为800 mg/m²/天时出现了剂量限制性毒性，表现为情绪改变、嗜睡、定向障碍以及伴有脑电图异常的认知功能障碍。推荐的II期剂量水平为：采用5天推注给药方案时为525 mg/m²/天，采用持续静脉输注给药方案时为650 mg/m²/天。由于输注部位出现静脉疼痛，该药物必须通过中心静脉通路给药。卡醋胺外周和中枢副作用的病理生理学机制可能与胆碱能活性增加有关。
