Piccart M J, Bruning P, Wildiers J, Awada A, Schornagel J H, Thomas J, Tomiak E, Bartholomeus S, Witteveen P O, Paridaens R
Jules Bordet Institute, Brussels, Belgium.
Ann Oncol. 1995 Sep;6(7):673-7. doi: 10.1093/oxfordjournals.annonc.a059283.
In an attempt to increase chemotherapy dose intensity by step-wise reduction of the time interval between treatment cycles, filgrastim was administered to breast cancer patients receiving a three-month combination chemotherapy with epirubicin (E) and cyclophosphamide (C).
Chemotherapy-naïve patients with locally advanced or metastatic breast cancer received fixed doses of E (120 mg/m2) and C 9830 mg/m2) by 15-min i.v. infusion on day 1 of each cycle and filgrastim at a dose of 4 micrograms/kg once daily by SC injection starting 24 hours after chemotherapy. Cohorts of patients were treated in successive schedules, each schedule corresponding to a specified time interval between chemotherapy cycles. The toxicity observed in each schedule was evaluated before patients were accrued to the next schedule, which corresponded to a shorter time interval between chemotherapy cycles.
The maximum tolerated schedule was E (120 mg/m2) plus C 9830 mg/m2) given every 14 days with filgrastim support from day 2 until day 13. On this schedule, 5 of 12 patients experienced dose-intensity-limiting toxicities (DLT) during the 3-month study period. Non-hematological DLT occurred in 2/12 patients (mucositis, skin toxicity) while /312 experienced febrile neutropenia requiring i.v. antibiotics. All patients achieved recovery of ANC to >1.5 x 10(9)/l by the time of scheduled retreatment. The combination of filgrastim with this regimen did not seem to add major toxicities. The efficacy was high, with 87% of patients achieving an objective response and a median response duration of 18 months (range: 4-52 months).
Filgrastim permits at 33% increase in 'EC' dose intensification over that of the conventional every-3-week administration. Randomized studies should now be initiated to evaluate the merit, if any, of 'accelerated' chemotherapy in advanced breast cancer.
为了通过逐步缩短治疗周期之间的时间间隔来提高化疗剂量强度，对接受表柔比星（E）和环磷酰胺（C）三个月联合化疗的乳腺癌患者给予非格司亭。
初治的局部晚期或转移性乳腺癌患者在每个周期的第1天通过15分钟静脉输注接受固定剂量的E（120mg/m²）和C（830mg/m²），并在化疗后24小时开始每天一次皮下注射剂量为4μg/kg的非格司亭。患者队列按连续方案进行治疗，每个方案对应化疗周期之间的特定时间间隔。在将患者纳入下一个方案（对应化疗周期之间更短的时间间隔）之前，评估每个方案中观察到的毒性。
最大耐受方案是每14天给予E（120mg/m²）加C（830mg/m²），并从第2天至第13天给予非格司亭支持。在此方案下，12名患者中有5名在3个月的研究期间出现剂量强度限制毒性（DLT）。2/12名患者出现非血液学DLT（粘膜炎、皮肤毒性），而3/12名患者经历了需要静脉使用抗生素的发热性中性粒细胞减少。所有患者在计划再次治疗时ANC均恢复至>1.5×10⁹/L。非格司亭与该方案联合使用似乎并未增加主要毒性。疗效较高，87%的患者获得客观缓解，中位缓解持续时间为18个月（范围：4 - 52个月）。
与传统的每3周给药相比，非格司亭可使“EC”剂量强度提高33%。现在应启动随机研究，以评估晚期乳腺癌“加速”化疗的益处（如果有的话）。
