Amadori D, Frassineti G L, De Matteis A, Mustacchi G, Santoro A, Cariello S, Ferrari M, Nascimben O, Nanni O, Lombardi A, Scarpi E, Zoli W
Divisione di Oncologia Medica, Ospedale L. Pierantoni, Forlì, Italy.
Breast Cancer Res Treat. 1998 Jun;49(3):209-17. doi: 10.1023/a:1006063412726.
Previous results from our preclinical studies have shown that lonidamine (LND) can positively modulate the antiproliferative activity of doxorubicin (DOX) on breast cancer cell lines. To evaluate the effect of LND in a clinical setting, a multicenter randomized trial was carried out on patients with advanced breast cancer. From September 1991 to July 1993, 181 patients were enrolled in the trial and received an initial treatment of DOX at 75 mg/m2 for 3 cycles. The 137 patients who reached complete remission, partial remission, or stable disease were randomized to receive either DOX alone (75 mg/m2 day 1) (arm A) or DOX plus LND (600 mg orally/day) (arm B). The patients enrolled in the two arms were fairly homogeneous in terms of major clinical characteristics. Toxicity was similar in both arms except for myalgia: WHO grade > or=2 was observed in 57% of arm B patients. Overall response rate to DOX + LND was 50% and to DOX alone 38% in evaluable patients, and 48% vs 37% in all registered patients, as determined by an intention-to-treat analysis. The differences did not reach statistical significance. Conversely, in agreement with previous findings, we observed a significant difference in response rate in the subgroup of patients with liver metastases, regardless of the extent of hepatic involvement (DOX + LND 68% vs DOX 33%, p=0.03). This observation makes LND an important tool in association with anthracyclines in the treatment of this subgroup of patients.
我们临床前研究的先前结果表明，氯尼达明（LND）可正向调节阿霉素（DOX）对乳腺癌细胞系的抗增殖活性。为了评估LND在临床环境中的作用，对晚期乳腺癌患者进行了一项多中心随机试验。从1991年9月至1993年7月，181名患者入组该试验，并接受了初始治疗，即阿霉素75mg/m²，共3个周期。137名达到完全缓解、部分缓解或病情稳定的患者被随机分为两组，一组单独接受阿霉素治疗（75mg/m²，第1天）（A组），另一组接受阿霉素加氯尼达明治疗（口服600mg/天）（B组）。两组入组患者在主要临床特征方面相当一致。除肌痛外，两组毒性相似：B组57%的患者观察到世界卫生组织（WHO）≥2级肌痛。根据意向性分析，可评估患者中，阿霉素加氯尼达明的总体缓解率为50%，单独使用阿霉素为38%；所有登记患者中，该比例分别为48%和37%。差异未达到统计学显著性。相反，与先前的研究结果一致，我们观察到肝转移患者亚组的缓解率存在显著差异，无论肝脏受累程度如何（阿霉素加氯尼达明组为68%，阿霉素组为33%，p = 0.03）。这一观察结果使氯尼达明成为与蒽环类药物联合用于治疗该亚组患者的重要工具。
