Buzdar A U, Hortobagyi G N, Kau S W, Smith T L, Fraschini G, Holmes F A, Gutterman J U, Hug V M, Singletary S E, Ames F C
Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030.
J Clin Oncol. 1992 Oct;10(10):1540-6. doi: 10.1200/JCO.1992.10.10.1540.
A prospective study in breast cancer patients was undertaken to determine whether escalating doses of doxorubicin and cyclophosphamide would result in a higher fraction of patients free of disease, and to evaluate the role of leukocyte alpha-interferon.
Between 1982 and 1986, 319 consecutive patients with stage II or III breast cancer with one or more positive nodes were assigned randomly to receive adjuvant chemotherapy that consisted of escalating doses of doxorubicin and cyclophosphamide in combination with vincristine and prednisone or the same chemotherapy regimen followed by 1 year of leukocyte alpha-interferon. Doxorubicin was administered by 72-hour continuous infusion through a central venous catheter (maximum total cumulative dose, 430 mg/m2). All patients with positive or unknown estrogen receptor status were also given tamoxifen for 1 year.
The median follow-up was 71 months (range, 35 to 99 months). Correlation of disease-free survival (DFS) with dose-intensity of cyclophosphamide and doxorubicin showed no improvement in DFS for patients who were able to receive escalated drug doses compared with those who were not. Doxorubicin administered by continuous infusion was associated with a negligible risk of cardiotoxicity in this study despite the administration of higher accumulative doses than in our previous adjuvant therapy studies. The DFS rates of patients who did and those who did not receive leukocyte alpha-interferon were similar.
In this study, there was no real evidence that higher drug dose intensity was associated with longer DFS. Leukocyte alpha-interferon as it was used in this study had no therapeutic value. Doxorubicin administered by infusion was associated with a reduced risk of cardiotoxicity.
对乳腺癌患者进行一项前瞻性研究，以确定递增剂量的阿霉素和环磷酰胺是否会使无病患者比例更高，并评估白细胞α-干扰素的作用。
1982年至1986年期间，319例连续的II期或III期乳腺癌且有一个或多个阳性淋巴结的患者被随机分配接受辅助化疗，化疗方案为递增剂量的阿霉素和环磷酰胺联合长春新碱和强的松，或相同化疗方案后加用1年的白细胞α-干扰素。阿霉素通过中心静脉导管进行72小时持续输注（最大总累积剂量为430mg/m²）。所有雌激素受体状态为阳性或未知的患者还接受了1年的他莫昔芬治疗。
中位随访时间为71个月（范围35至99个月）。无病生存期（DFS）与环磷酰胺和阿霉素剂量强度的相关性显示，与未能接受递增药物剂量的患者相比，能够接受递增药物剂量的患者DFS并无改善。在本研究中，尽管阿霉素的累积剂量高于我们之前的辅助治疗研究，但通过持续输注给药时心脏毒性风险可忽略不计。接受和未接受白细胞α-干扰素的患者DFS率相似。
在本研究中，没有实际证据表明更高的药物剂量强度与更长的DFS相关。本研究中使用的白细胞α-干扰素没有治疗价值。通过输注给药的阿霉素心脏毒性风险降低。
