Derigs H G, Huber C, Mahlke M, Kolbe K
Abteilung für Hämatologie, Johannes Gutenberg-Universität, Mainz.
Geburtshilfe Frauenheilkd. 1996 Apr;56(4):190-7. doi: 10.1055/s-2007-1022258.
Current Status and Limits: High-dose chemotherapy with autologous haematopoietic stem cell rescue has become in recent years a widely accepted therapeutic modality for advanced stage breast cancer in North America. The emergence of modern supportive measures like peripheral blood stem cell rescue has significantly decreased the toxicity and cost of high-dose chemotherapy. The rationale for use of escalated chemotherapy doses in breast cancer is the establishment of a dose-response relationship, with higher doses producing increased response rates in preclinical studies as well as in clinical trials. The dose limiting myelotoxicity of several active agents in breast cancer can only be overcome by rescue with previously cryopreserved autologous haematopoietic stem cells. Two phase II clinical trials with high-dose chemotherapy as adjuvant measure in high-risk breast cancer patients with multiple positive axillary nodes have been published so far. Disease-free survival is these 2 studies was 71 and 84% after 5 and 3 years of follow-up, and hence significantly longer compared to historic controls. Randomised phase III trials are urgently needed to confirm these promising results. Several reports of high-dose chemotherapy in disseminated breast cancer have been published so far. Most of these studies could establish a high response rate of about 70%, half of which were complete responses. However, most tumour regressions were short lived and overall survival was not prolonged compared with historic controls. Therefore, high-dose chemotherapy cannot be recommended for disseminated breast cancer patients outside of innovative clinical trials. To improve on the results in disseminated breast cancer patients the use of repeated cycles of high dose chemotherapy or the value of tumour cell purging of the stem cell product are being currently explored by different groups. In general, breast cancer patients should only be treated with high dose chemotherapy in context with a clinical trial.
近年来，高剂量化疗联合自体造血干细胞救援已成为北美晚期乳腺癌广泛接受的治疗方式。外周血干细胞救援等现代支持措施的出现显著降低了高剂量化疗的毒性和成本。在乳腺癌中使用递增化疗剂量的理论依据是建立剂量反应关系，在临床前研究以及临床试验中，更高剂量可产生更高的反应率。乳腺癌中几种活性药物的剂量限制性骨髓毒性只能通过用先前冷冻保存的自体造血干细胞进行救援来克服。迄今为止，已发表了两项将高剂量化疗作为高危乳腺癌患者（多个腋窝淋巴结阳性）辅助治疗措施的II期临床试验。在这两项研究中，随访5年和3年后的无病生存率分别为71%和84%，因此与历史对照相比显著更长。迫切需要进行随机III期试验以证实这些有前景的结果。迄今为止，已发表了几篇关于转移性乳腺癌高剂量化疗的报告。这些研究大多能确立约70%的高反应率，其中一半为完全缓解。然而，大多数肿瘤缓解是短暂的，与历史对照相比总生存期并未延长。因此，对于转移性乳腺癌患者，除了创新性临床试验外，不推荐使用高剂量化疗。为了改善转移性乳腺癌患者的治疗结果，不同研究团队目前正在探索使用重复周期的高剂量化疗或干细胞产品肿瘤细胞清除的价值。一般来说，乳腺癌患者仅应在临床试验的背景下接受高剂量化疗。
