Meng Zhiqiang, Yang Peiying, Shen Yehua, Bei Wenying, Zhang Ying, Ge Yongqian, Newman Robert A, Cohen Lorenzo, Liu Luming, Thornton Bob, Chang David Z, Liao Zongxing, Kurzrock Razelle
International Center of Integrative Oncology, Fudan University Cancer Hospital, Shanghai, China.
Cancer. 2009 Nov 15;115(22):5309-18. doi: 10.1002/cncr.24602.
Huachansu, a Chinese medicine that comes from dried toad venom from the skin glands of Bufo gargarizans or B. melanostictus, has been used in the treatment of various cancers in China. The authors conducted a pilot study, using a phase 1 trial design, of huachansu in patients with advanced cancer.
Huachansu was administered intravenously for 14 days followed by 7 days off (1 cycle). Without significant adverse events or progressive disease, treatment continued beyond 2 cycles. The dose of huachansu was escalated as follows with 3 patients per cohort: 10 (level 1), 20 (level 2), 40 (level 3), 60 (level 4), and 90 (level 5) mL/m(2).
Fifteen patients (hepatocellular cancer, n = 11; nonsmall cell lung cancer, n = 2; pancreatic cancer, n = 2) were enrolled in the trial, and no dose-limiting toxicities (DLTs) were found. Eleven patients had no drug-related toxicity greater than grade 1. Six (40%) had stable disease (median duration, 6.0 months; range, 3.5-11.1 months). One of these patients (with hepatocellular cancer) had 20% regression (duration, 11 months) (dose level 1). Quality of life improved for patients with stable disease. Plasma bufalin concentration reached maximal levels at the end of the 2-hour infusion and was proportional to the amount of drug being administered (0.81-3.38 ng/mL).
No DLT was observed with the use of huachansu at doses up to 8x higher than typically used in China. Six patients had prolonged stable disease or minor tumor shrinkage.
华蟾素是一种源自中华大蟾蜍或黑眶蟾蜍皮肤腺干燥毒液的中药，在中国已被用于治疗多种癌症。作者采用1期试验设计，对晚期癌症患者进行了华蟾素的初步研究。
华蟾素静脉给药14天，随后停药7天（1个周期）。若无明显不良事件或疾病进展，则治疗持续超过2个周期。华蟾素剂量按以下方式递增，每个队列3例患者：10（1级）、20（2级）、40（3级）、60（4级）和90（5级）mL/m²。
15例患者（肝细胞癌11例、非小细胞肺癌2例、胰腺癌2例）入组该试验，未发现剂量限制性毒性（DLT）。11例患者无大于1级的药物相关毒性。6例（40%）病情稳定（中位持续时间6.0个月；范围3.5 - 11.1个月）。其中1例患者（肝细胞癌）肿瘤缩小20%（持续时间11个月）（剂量水平1）。病情稳定的患者生活质量有所改善。血浆蟾毒灵浓度在输注2小时结束时达到最高水平，且与给药量成正比（0.81 - 3.38 ng/mL）。
使用比中国通常使用剂量高8倍的华蟾素未观察到剂量限制性毒性。6例患者病情长期稳定或肿瘤轻微缩小。
