Cardoso F, Ferreira Filho A F, Crown J, Dolci S, Paesmans M, Riva A, Di Leo A, Piccart M J
Jules Bordet Institut, Brussels, Belgium.
Anticancer Res. 2001 Jan-Feb;21(1B):789-95.
Doxorubicin (A) and Docetaxel (T) are amongst the most active agents in breast cancer treatment. The impact of drug sequencing is an issue still under evaluation.
To evaluate the feasibility and tolerability of two A and T-based sequential regimens, in which the sequence of drug administration was reversed.
The study included patients pts aged < or = 70 years, with operable node positive breast cancer. Two consecutive groups of patients received one of the following regimens: 1) Sequential A-->T-->CMF: Doxorubicin 75 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by i.v. CMF days 1 and 8 q4wks x 3 cycles. 2) Sequential T-->A-->CMF: same doses for Doxorubicin and Docetaxel but reverse sequence of administration, followed by oral CMF (CPA 100 mg/m2, oral, days 1-14 + MTX 40 mg/m2, i.v., days 1 and 8 + 5FU 600 mg/m2, i.v., days 1 and 8, q4wks). An analysis of treatment administration and toxicity was performed for the first six cycles of CT, in the two treatment groups.
Group 1 with 20 patients and group 2 with 14 patients were balanced in terms of patient and tumour characteristics. There was one early treatment discontinuation in each group due to toxicity (one allergic and one skin reaction to docetaxel). Median relative dose intensity was 100% for both drugs in both groups. The most relevant side effects were (overall incidence, group 1 vs group 2): Myalgia: 45% vs 72%; Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis 65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic Fever 20% vs 21% and Fatigue 80% vs 93%. Grade 3/4 adverse events' rate was low in the two groups.
阿霉素（A）和多西他赛（T）是乳腺癌治疗中最有效的药物之一。药物给药顺序的影响仍是一个有待评估的问题。
评估两种基于A和T的序贯方案的可行性和耐受性，这两种方案中药物给药顺序相反。
该研究纳入年龄≤70岁、可手术的淋巴结阳性乳腺癌患者。连续两组患者接受以下方案之一：1）序贯A→T→CMF：阿霉素75mg/m²，静脉注射，第1天，每3周1次，共3个周期，随后多西他赛100mg/m²，静脉注射，第1天，每3周1次，共3个周期，随后静脉注射CMF，第1天和第8天，每4周1次，共3个周期。2）序贯T→A→CMF：阿霉素和多西他赛剂量相同，但给药顺序相反，随后口服CMF（环磷酰胺100mg/m²，口服，第1 - 14天 + 甲氨蝶呤40mg/m²，静脉注射，第1天和第8天 + 氟尿嘧啶600mg/m²，静脉注射，第1天和第8天，每4周1次）。对两个治疗组CT的前六个周期进行治疗给药和毒性分析。
第1组20例患者和第2组14例患者在患者和肿瘤特征方面均衡。每组各有1例因毒性导致早期治疗中断（1例对多西他赛过敏，1例对多西他赛有皮肤反应）。两组中两种药物的中位相对剂量强度均为100%。最相关的副作用为（总体发生率，第1组 vs 第2组）：肌痛：45% vs 72%；关节痛：15% vs 57%；皮肤：35% vs 57%；神经感觉：55% vs 64%；口腔炎65% vs 36%；结膜炎25% vs 57%；中性粒细胞减少性发热20% vs 21%；疲劳80% vs 93%。两组3/4级不良事件发生率较低。
1）由于治疗给药优化且G3 - G4级副作用发生率有限，两种给药顺序均被认为可行。2）来格司亭的同时使用可能部分解释了所报道的肌痛和关节痛发生率。3）由于患者数量有限，无法就最耐受的方案得出结论。
