Tormey D C, Simon R, Falkson G, Bull J, Band P, Perlin E, Blom J
Cancer Res. 1977 Feb;37(2):529-34.
A phase 1 to 2 evaluation of a combination of adriamycin (ADR) and dibromodulcitol (DBD) was performed in patients with progressive, metastatic breast carcinoma. All but one patient had been treated previously with chemotherapy. ADR was given on Day 1 or Days 1 and 8, and DBD was given on Days 1 to 10 of each 21- to 28-day treatment cycle. Side effects were evaluable in 54 patients, and 50 patients were evaluable for therapeutic response. The dose-limiting toxicities were leukopenia and thrombocytopenia. The severity of both toxicities increased as both the ADR and DBD doses increased; however, the effect of increases in DBD dose was much more profound. The mean white blood cell count and platelet nadirs occurred, respectively, on Days 15.3 and 15.9; both nadirs were delayed for 0.6 day by each 30-mg/sq m/day increase in the DBD dose and delayed for 1.7 to 3.9 days using the Day 1, 8 rather than the Day 1 ADR schedule Recovery of the peripheral counts by Day 29 was prolonged by the Day 1, 8 ADR schedule and by increasing the DBD dose. A tolerable dose schedule for previously treated patients was considered to be ADR, 40 mg/sq m on Day 1, and DBD, 135 mg/sq m on Days 1 to 10 repeated every 28 days. Responses were observed in 46% (23 of 50) of the patients. There were 1 complete remission, 19 partial remissions, and 3 improvements. Thirteen patients showed no change and 14 developed progressive disease. There were responses in 13 of 37 (36%) with visceral dominant disease as compared to 7 of 8 (87%) with osseous and 3 of 5 (60%) with soft tissue-dominant disease. There were 22 of 48 (46%) responses in patients previously exposed to alkylating agent therapy. Twnety-two patients had responded and 19 had failed to respond to prior alkylating agent-containing regimens; the response rates to DBD in these groups were respectively, 45 and 42%. The median time to remission was 29 days. The median time to therapeutic failure was 5.1 months for responders, 2.3 months for patients with no change, and 29 days for progressors. The combination of ADR and DBD appears to be an active and well-tolerated program in patients with previously treated metastatic breast carcinoma.
对阿霉素（ADR）和二溴卫矛醇（DBD）联合用药进行了1至2期评估，受试对象为进展期转移性乳腺癌患者。除1例患者外，其他所有患者此前均接受过化疗。在每21至28天的治疗周期中，ADR于第1天或第1天和第8天给药，DBD于第1天至第10天给药。54例患者的副作用可评估，50例患者的治疗反应可评估。剂量限制性毒性为白细胞减少和血小板减少。随着ADR和DBD剂量的增加，两种毒性的严重程度均增加；然而，DBD剂量增加的影响更为显著。平均白细胞计数和血小板最低点分别出现在第15.3天和第15.9天；DBD剂量每增加30mg/平方米/天，两个最低点均延迟0.6天，采用第1天、第8天而非第1天的ADR给药方案时，最低点延迟1.7至3.9天。第29天外周血细胞计数的恢复因第1天、第8天的ADR给药方案和DBD剂量增加而延长。对于先前接受过治疗的患者，可耐受的给药方案被认为是ADR在第1天为40mg/平方米，DBD在第1天至第10天为135mg/平方米，每28天重复一次。50例患者中有46%（23例）出现反应。有1例完全缓解，19例部分缓解，3例病情改善。13例患者无变化，14例病情进展。在内脏为主型疾病的37例患者中有13例（36%）出现反应，相比之下，骨转移为主型的8例患者中有7例（87%），软组织为主型的5例患者中有3例（60%）出现反应。在先前接受过烷化剂治疗的患者中，48例中有22例（46%）出现反应。22例患者对先前含烷化剂的治疗方案有反应，19例无反应；这些组中对DBD的反应率分别为45%和42%。缓解的中位时间为29天。有反应者治疗失败的中位时间为5.1个月，无变化者为2.3个月，病情进展者为29天。ADR和DBD联合用药似乎是先前接受过治疗的转移性乳腺癌患者的一种有效且耐受性良好的方案。
