HIGH-DOSE, DOSE-INTENSIVE CHEMOTHERAPY WITH DOXORUBICIN AND CYCLOPHOSPHAMIDE FOR THE TREATMENT OF ADVANCED BREAST-CANCER
HIGH-DOSE, DOSE-INTENSIVE CHEMOTHERAPY WITH DOXORUBICIN AND CYCLOPHOSPHAMIDE FOR THE TREATMENT OF ADVANCED BREAST-CANCER
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DOI：
10.1038/bjc.1993.151
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发表时间：
1993-04-01
影响因子：
8.8
通讯作者：
HOWELL, A
中科院分区：
文献类型：
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作者：
FERGUSON, JE;DODWELL, DJ;HOWELL, A
18例晚期乳腺癌患者开始接受高剂量阿霉素（100 mg m-2）或阿霉素（100 mg m-2）和环磷酰胺（500 mg m-2）治疗，每2周间隔一次。计划进行三个疗程的治疗。rG-CSF在每个周期化疗后24小时开始皮下注射，持续10天。18例患者中有16例（89%）缓解，其中6例（33%）完全缓解。12例（67%）完成了三个计划周期，4例（22%）接受了两个周期，2例（11%）只接受了一个周期。中位进展时间为5个半月，中位生存期为18个半月。中性粒细胞减少发生在89%的疗程后，65%的疗程伴有显著（世卫组织III级或IV级）感染。中性粒细胞减少持续时间短（平均5.4天），从治疗开始到绝对中性粒细胞计数恢复（ANC > 1000 x 10(6)升）的平均时间为11天。43%的疗程伴有中度至重度上皮毒性（WHO分级3或4级），且剂量有限。结论：高剂量、高剂量强化化疗对晚期乳腺癌具有良好的初始治疗效果，但并没有延长缓解期或延长总生存期。虽然皮下注射rG-CSF大大缩短了中性粒细胞减少的预期持续时间，但中性粒细胞减少和需要静脉注射抗生素的感染的总体发生率很高。此外，几乎一半的疗程伴有中度至重度口腔黏膜炎和/或轻度至中度掌和足底炎症。缺乏生存效益和过量的毒性严重限制了该方案的广泛应用。它不应该用来代替标准剂量的姑息性化疗转移性乳腺癌。
Eighteen patients with advanced breast cancer were commenced on treatment with high dose doxorubicin (100 mg m-2) or doxorubicin (100 mg m-2) and cyclophosphamide (500 mg m-2) at 2 weekly intervals. Three cycles of treatment were planned. rG-CSF was given subcutaneously for 10 days, starting 24 h after each cycle of chemotherapy. Sixteen out of 18 patients responded (89%) of whom six (33%) achieved a complete remission. Twelve (67%) completed the three planned cycles, four (22%) received two cycles and two (11%) received one cycle only. The median time to progression was 5 1/2 months and the median survival was 18 1/2 months. Neutropenia occurred after 89% of courses and 65% of courses were accompanied by a significant (WHO grade III or IV) infection. The duration of neutropenia was short (mean 5.4 days) and mean time to absolute neutrophil count recovery (ANC > 1,000 x 10(6) litre) from the start of treatment was 11 days. Moderate to severe epithelial toxicity (WHO grade 3 or 4) accompanied 43% of courses and was dose limiting. Conclusion: High dose, dose intensive chemotherapy has an excellent initial therapeutic effect in advanced breast cancer but does not prolong duration of remission or overall survival beyond that of standard treatment. Although subcutaneous rG-CSF curtailed the expected duration of neutropenia substantially, the overall incidence of neutropenia and of infections requiring intravenous antibiotics was high. Furthermore, almost half of the courses were complicated by moderate to severe oral mucositis and/or mild to moderate palmar and plantar inflammation. The lack of survival benefit and excess toxicity seriously limits the wider application of this regime. It should not be used in place of standard dose palliative chemotherapy for metastatic breast cancer.