Patnaik A, MacKinnon J, Goss P, Nagy T, Stewart K, Keating A, Crump M
Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Canada.
J Clin Oncol. 2000 Jun;18(12):2363-8. doi: 10.1200/JCO.2000.18.12.2363.
To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high complete and overall response rates in metastatic breast cancer (MBC).
Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline-based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m(2)/d and mitoxantrone 16 mg/m(2)/d combined with escalating doses of carboplatin 200 to 500 mg/m(2)/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 microg/d subcutaneously starting on day 1.
A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with < or = 400 mg/m(2) of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 10(9)/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 10(9)/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6).
The maximum-tolerated dose of carboplatin was 400 mg/m(2)/d in combination with mitoxantrone 16 mg/m(2)/d and cyclophosphamide 1,500 mg/m(2), all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment.
强化一种高剂量环磷酰胺、米托蒽醌和卡铂的治疗方案，该方案先前在转移性乳腺癌（MBC）中产生了较高的完全缓解率和总缓解率。
44例年龄中位数为43岁（范围25至57岁）且先前未接受过治疗的MBC患者，对基于蒽环类药物或单药紫杉烷化疗有反应，接受环磷酰胺1.5 g/m²/d和米托蒽醌16 mg/m²/d，联合递增剂量的卡铂200至500 mg/m²/d，每种药物均在第-6天至-3天每日给药。造血功能通过在第0天输注动员的外周血干细胞以及从第1天开始皮下使用粒细胞-巨噬细胞集落刺激因子300 μg/d来支持。
共检查了六个剂量水平的卡铂。3级和4级毒性分别发生在10例和1例患者中，在接受≤400 mg/m²卡铂治疗的31例患者中，仅5例发生3级毒性。主要的剂量限制性毒性为心脏、肺部和肾脏毒性。4例患者发生充血性心力衰竭：2例在外周血干细胞移植（PBSCT）后11个月和36个月时射血分数持续较低，2例恢复。血液学恢复至绝对中性粒细胞计数大于0.5×10⁹/L的中位时间为11天（范围8至25天），血小板计数大于20×10⁹/L的中位时间为10.5天（范围6至60天）。有2例因败血症导致的毒性死亡：1例在第27天（5级），1例在第42天因心脏骤停死亡（6级）。
卡铂的最大耐受剂量为400 mg/m²/d，联合米托蒽醌16 mg/m²/d和环磷酰胺1500 mg/m²，所有药物在4天内给药。该方案正在一项高剂量化疗和PBSCT与标准治疗对比的III期试验中进行测试。
