Induction chemotherapy of dibromodulcitol, Adriamycin, vincristine, tamoxifen, and Halotestin with methotrexate in metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1181).
Induction chemotherapy of dibromodulcitol, Adriamycin, vincristine, tamoxifen, and Halotestin with methotrexate in metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1181).
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二溴调节醇、阿霉素、长春新碱、他莫昔芬和氟甲氨蝶呤联合甲氨蝶呤治疗转移性乳腺癌的诱导化疗：一项东部肿瘤合作组研究 (E1181)。
DOI：
10.1097/00000421-199802000-00023
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Falkson,G
中科院分区：
文献类型：
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作者：
Chang,AY;Putt,M;Pandya,KJ;Harris,J;Gelman,R;Tormey,DC;Falkson,G
患有转移性乳腺癌的患者很少能治愈。按常规剂量和方案进行化疗通常可使10%至20%的患者完全缓解。本研究旨在确定1)二溴调制醇、阿霉素®、长春新碱、他莫昔芬、Halotstin®和甲氨蝶呤联合亚叶酸钙救援方案(DAVTHML)是否能产生50%的完全缓解率；以及2)这种组合对化疗未治疗的转移性乳腺癌患者的毒性。DAVTHML诱导化疗共6个28天周期，第1~10天口服二溴调制醇135 mg/m2；第1天静脉滴注阿霉素45 mg/m2；第1天静脉滴注长春新碱2 mg；他莫昔芬和氟替汀每日20 mg；甲氨蝶呤800 mg/m2静脉滴注第15天和第22天；亚叶酸钙15 mg/m2口服，每6小时1次，共9次，从甲氨蝶呤治疗后4小时开始。诱导后，病情稳定或部分反应的患者接受环磷酰胺、甲氨蝶呤和基于5-氟尿嘧啶的方案(CMF)治疗。完全缓解的患者在完全缓解后再接受3个周期的DAVTHML治疗，然后观察停止治疗直到复发，然后再次给予DAVTHML。58名患者被纳入这项研究。在诱导期间，26%的符合条件的患者经历了完全缓解；总体应答率为80%。符合条件的患者治疗失败的中位时间为11.1个月，中位生存期为24.0个月。当所有患者都被纳入评估时，这一点没有显著变化。3年和5年生存率分别为37%和11%。符合条件的患者中有90%经历了III或IV级毒性。它们是白细胞减少(75%)、贫血(20%)、血小板减少(20%)和呕吐(17%)。治疗过程中未发现致死性毒性反应，但有1名患者后来死于二溴代谢醇引起的骨髓增生异常综合征。我们研究的总体反应和完全缓解率令人振奋。DAVTHML的毒性是可耐受的，但二溴代谢醇引起的骨髓增生异常综合征除外。使用周期中期非骨髓抑制药来提高完全缓解率的概念是可行的。
Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin®, vincristine, tamoxifen, Halotestin®, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m 2 perorally days 1 to 10; Adriamycin® m 45 mg/m 2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin®, 20 mg perorally daily; methotrexate, 800 mg/m 2 intravenously days 15 and 22; and leucovorin, 15 mg/m 2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.