Phase I trial of sequential high-dose chemotherapy with escalating dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.
Phase I trial of sequential high-dose chemotherapy with escalating dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.
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发表时间：
1998-07
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通讯作者：
L. Vahdat;K. Papadopoulos;C. Balmaceda;T. McGovern;J. Dunleavy;E. Kaufman;B. Fung;T. Garrett;D. Savage;A. Tiersten;J. Ayello;E. Bagiella;D. Heitjan;K. Antman;C. Hesdorffer
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作者：
L. Vahdat;K. Papadopoulos;C. Balmaceda;T. McGovern;J. Dunleavy;E. Kaufman;B. Fung;T. Garrett;D. Savage;A. Tiersten;J. Ayello;E. Bagiella;D. Heitjan;K. Antman;C. Hesdorffer
一个单一的高剂量化疗周期与干细胞支持可以产生至少3年的无病生存率为15-20%的妇女与响应阶段IV乳腺癌。北美自体骨髓移植登记数据表明，完全缓解（CR）是与无病生存期延长相关的唯一最重要的预后因素。因此，如果序贯大剂量化疗可以提高CR率，那么可能会有更多的患者保持无病状态。对诱导化疗至少有部分反应（PR）的妇女接受三个独立的高剂量化疗周期，外周血祖细胞支持和粒细胞集落刺激因子。第一次强化是紫杉醇（400-825 mg/ m2）剂量递增，第二次强化是美法仑（180 mg/m2），第三次强化包括6000 mg/m2环磷酰胺（1500 mg/m2/天）、500 mg/m2塞替派（125 mg/m2/天）和800 mg/m2卡铂（200 mg/m2/天; CTCb）。36名妇女入组，31名妇女完成了所有三个周期。紫杉醇输注后，大多数患者发生可逆性感觉神经病变。在19例有可测量疾病的患者中，6例转化为CR，7例转化为PR*（所有软组织或内脏疾病伴既往溶骨性病变硬化完全消退），2例进一步PR，总缓解率为79%。两名患者没有进一步的反应，两名患者的疾病进展，因此他们在CTCb之前退出研究。78%的患者在中位随访14个月（范围3-24+）时无进展。三个连续周期的高剂量化疗是可行的，在这项研究中没有死亡率。剂量高达825 mg/m2的紫杉醇单药耐受性良好，具有中度可逆毒性。
A single high-dose cycle of chemotherapy with stem cell support can produce disease-free survival of 15-20% for at least 3 years in women with responding stage IV breast cancer. North American Autologous Bone Marrow Transplant Registry data suggest that a complete response (CR) is the single most important prognostic factor associated with prolonged disease-free survival. Therefore, if sequential high-dose chemotherapy can increase the CR rate, then perhaps an increased proportion of patients will remain disease free. Women with at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and granulocyte colony-stimulating factor. The first intensification was a dose escalation of paclitaxel (400-825 mg/ m2), the second intensification was melphalan (180 mg/m2), and the third intensification consisted of 6000 mg/m2 cyclophosphamide (1500 mg/m2/day), 500 mg/m2 thiotepa (125 mg/m2/day), and 800 mg/m2 carboplatin (200 mg/m2/day; CTCb). Thirty-six women were enrolled and 31 completed all three cycles. After the paclitaxel infusion most patients developed reversible predominantly sensory neuropathy. Of the 19 patients with measurable disease, 6 converted to CR, 7 converted to a PR* (the complete resolution of all soft tissue or visceral disease with sclerosis of prior lytic bone lesions), and 2 had a further PR for an overall response rate of 79%. Two patients had no further response and disease in two patients progressed, and thus they were taken off the study before CTCb. Seventy-eight percent are progression-free at a median follow-up of 14 months (range, 3-24+). Three sequential cycles of high-dose chemotherapy are feasible and were administered in this study with no mortality. Single agent paclitaxel at doses up to 825 mg/m2 were well tolerated with moderate reversible toxicity.