Burdette-Radoux Susan, Wood Marie E, Olin Julie J, Laughlin Rebecca S, Crocker Abigail M, Ashikaga Takamaru, Muss Hyman B
Vermont Cancer Center, University of Vermont, Burlington, Vermont 05401, USA.
Breast J. 2007 May-Jun;13(3):274-80. doi: 10.1111/j.1524-4741.2007.00421.x.
This phase I/II trial investigates the safety and feasibility of six cycles of concurrent taxane, anthracycline and cyclophosphamide on a dose dense schedule. Patients with stage II/III breast cancer were treated with docetaxel (T) 75 mg/m(2), epirubicin (E) 75 mg/m(2) (cohort 1, n = 3) or 100 mg/m(2) (cohort 2, n = 12), and cyclophosphamide (C) 500 mg/m(2) IV on day 1, with pegfilgrastim 6 mg subcutaneously on day 2, every 2 weeks for six cycles. Patients were assessed for toxicity every 2 weeks; cardiac function and response (if neoadjuvant) were assessed after six cycles. All patients in cohort 1 received 100% planned dose intensity; in cohort 2, five of twelve patients received 100% and 11/12 received >80%. There were no dose reductions or delays for day 1 myelotoxicity. Dose reductions as a result of febrile neutropenia (FN) occurred in cohort 2, with six of twelve patients experiencing FN in seven of sixty-nine cycles. Six patients had anemia > or =grade 3; five received RBC transfusion and seven received an erythropoietic growth factor. Four patients required dose reductions for nonhematologic toxicity (two mucositis; one neurotoxicity; one diarrhea + cellulitis). Four patients developed thrombophlebitis, which was associated with FN in one of four. Two of fourteen evaluable patients had asymptomatic decreases in LVEF >10%; all remained within normal range. All four patients receiving neoadjuvant TEC had significant clinical responses (one CR, three PR). No pathologic CRs were seen.
Dose dense TEC chemotherapy is feasible, has acceptable toxicity at doses equivalent to TAC (docetaxel 75 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide 600 mg/m(2)), and has moderate but manageable toxicity using a higher epirubicin dose of 100 mg/m(2), with FN occurring in six of twelve patients at the higher dose.
本I/II期试验研究了六个周期的多西他赛、蒽环类药物和环磷酰胺按剂量密集方案联合使用的安全性和可行性。II/III期乳腺癌患者接受多西他赛（T）75mg/m²、表柔比星（E）75mg/m²（队列1，n = 3）或100mg/m²（队列2，n = 12），以及环磷酰胺（C）500mg/m²静脉注射，第1天给药，第2天皮下注射培非格司亭6mg，每2周进行六个周期。每2周对患者进行毒性评估；六个周期后评估心脏功能和反应（如果是新辅助治疗）。队列1中的所有患者接受了100%计划剂量强度；在队列2中，12名患者中有5名接受了100%，12名中有11名接受了>80%。第1天的骨髓毒性未出现剂量减少或延迟。队列2中因发热性中性粒细胞减少（FN）导致剂量减少，12名患者中有6名在69个周期中的7个周期出现FN。6名患者贫血≥3级；5名接受了红细胞输血，7名接受了促红细胞生成生长因子。4名患者因非血液学毒性需要减少剂量（2名口腔炎；1名神经毒性；1名腹泻+蜂窝织炎）。4名患者发生血栓性静脉炎，其中4名中有1名与FN相关。14名可评估患者中有2名左心室射血分数（LVEF）无症状下降>10%；均仍在正常范围内。所有4名接受新辅助TEC治疗的患者均有显著临床反应（1名完全缓解，3名部分缓解）。未观察到病理完全缓解。
剂量密集TEC化疗是可行的，在与TAC（多西他赛75mg/m²、表柔比星75mg/m²、环磷酰胺600mg/m²）等效的剂量下具有可接受的毒性，使用100mg/m²的更高表柔比星剂量具有中度但可管理的毒性，12名患者中有6名在更高剂量下出现FN。
