Mansi J L, de Graeff A, Newell D R, Glaholm J, Button D, Leach M O, Payne G, Smith I E
Breast Unit, Royal Marsden Hospital, Sutton, Surrey.
Br J Cancer. 1991 Sep;64(3):593-7. doi: 10.1038/bjc.1991.356.
Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity. In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24+ months) and three (11%) a minor response. Two patients have stable disease (greater than 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required. Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity. Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.
氯尼达明是一种具有独特作用机制的取代吲唑羧酸，早期临床研究已报道其具有抗肿瘤活性。在一项II期研究中，32例先前接受过治疗的晚期乳腺癌患者口服氯尼达明，每日分剂量为600mg。在28例可评估反应的患者中，3例（11%）获得部分缓解（4 - 24 +个月），3例（11%）获得轻微缓解。2例患者病情稳定（超过3个月），20例病情进展。毒性非常轻微。31例患者中有16例（53%）出现肌痛，持续时间中位数为2周。对4例患者进行了核磁共振波谱研究，但这些变化与肌痛程度无关。未观察到其他主要副作用，也无需减量。在治疗开始1个月后，对17例患者的氯尼达明药代动力学进行了研究。所有患者的血浆中均检测到氯尼达明，但氯尼达明水平与临床反应或毒性之间没有明确关系。氯尼达明似乎对晚期乳腺癌有活性，其低毒性将允许与化疗进行联合研究。
