Heidemann E, Stoeger H, Souchon R, Hirschmann W-D, Bodenstein H, Oberhoff C, Fischer J T, Schulze M, Clemens M, Andreesen R, Mahlke M, König M, Scharl A, Fehnle K, Kaufmann M
Department of Hematology and Medical Oncology, Deaconess Hospital, Oncological Center of Stuttgart, Germany.
Ann Oncol. 2002 Nov;13(11):1717-29. doi: 10.1093/annonc/mdf306.
To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment.
A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status.
After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment.
No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.
确定高危转移性乳腺癌患者一线接受联合化疗是否能从中获益。
共有260例符合高危标准、转移性疾病此前未接受过化疗且有可测量病灶的转移性乳腺癌女性患者，被随机分为两组，一组每3周接受米托蒽醌12mg/m²治疗，另一组接受氟尿嘧啶500mg/m²、表柔比星50mg/m²和环磷酰胺500mg/m²（FEC）的联合治疗。治疗持续至完全缓解加两个周期，或直至疾病进展。若为部分缓解或病情稳定，12个周期后停止治疗。二线治疗采用长春地辛、丝裂霉素和泼尼松龙。使用由疾病进展时间、患者对治疗获益的评分、脱发、呕吐和体能状态组成的改良布鲁纳评分来评估治疗获益。
在1992年至1997年招募患者并于1997年至1999年进行观察后，最终评估显示，在缓解率、客观缓解率、缓解持续时间、缓解时间、最佳缓解时间、疾病进展时间或总生存期方面，米托蒽醌单药治疗与FEC联合治疗无显著差异。然而，使用改良布鲁纳评分评估治疗获益时，单药治疗组有显著差异。没有证据表明任何亚组接受联合治疗效果更好。
在缓解或生存方面，米托蒽醌单药治疗与低剂量FEC联合治疗未检测到显著差异；因此，高危转移性乳腺癌患者一线联合化疗必要性的紧迫性可能受到质疑。由于毒性和生活质量评分有利于米托蒽醌单药治疗组，对于更看重生活质量而非可能轻微延长生存期的患者，可提供这种治疗。
