Fennelly D W, Aghajanian C, Shapiro F, O'Flaherty C, O'Connor K, Curtin J P, Crown J P, Hoskins W J, Spriggs D R
Department of Medical and Gynecologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Semin Oncol. 1997 Feb;24(1 Suppl 2):S2-26-S2-30.
A phase I study of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given in combination with high-dose carboplatin was conducted to identify the antitumor efficacy and maximum tolerated dose of paclitaxel in patients who had received sequential cycles of paclitaxel/cyclophosphamide as prior treatment for ovarian carcinoma. Eighteen patients with advanced ovarian cancer were treated in this study. Induction therapy consisted of two cycles of cyclophosphamide 3.0 g/m2 plus high-dose paclitaxel 300 mg/m2 plus filgrastim and leukapheresis to harvest peripheral blood progenitor cells, followed by four courses of rapidly cycled high-dose carboplatin with planned dose escalation of paclitaxel (150, 200, 250, and 300 mg/m2) rescued with peripheral blood progenitor cells. The study was amended after accrual of 11 patients, and the remaining seven patients received a single cycle of induction therapy with paclitaxel/cyclophosphamide, followed by four courses of rapidly cycled high-dose carboplatin with planned dose escalation of paclitaxel through levels 200 and 250 mg/m2. All 18 patients have completed therapy. Of the 15 who are evaluable for response, the pathologic complete response was 33% (five of 15 patients). The administration of escalating doses of paclitaxel in combination with high-dose carboplatin following sequential cycles of paclitaxel/cyclophosphamide induction resulted in significant nonhematopoietic toxicity. Induction with a single cycle of paclitaxel/cyclophosphamide resulted in excellent progenitor cell mobilization, and significantly ameliorated the toxicity of this approach. The response rates thus far obtained are promising and warrant further evaluation.
开展了一项I期研究，给予递增剂量的紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）联合大剂量卡铂，以确定在先前接受过紫杉醇/环磷酰胺序贯治疗卵巢癌的患者中，紫杉醇的抗肿瘤疗效和最大耐受剂量。本研究治疗了18例晚期卵巢癌患者。诱导治疗包括两个周期的环磷酰胺3.0 g/m²加紫杉醇300 mg/m²加非格司亭以及白细胞分离术以采集外周血祖细胞，随后进行四个疗程的快速循环大剂量卡铂，并计划递增紫杉醇剂量（150、200、250和300 mg/m²），用外周血祖细胞进行解救。在纳入11例患者后对研究进行了修正，其余7例患者接受了一个周期的紫杉醇/环磷酰胺诱导治疗，随后进行四个疗程的快速循环大剂量卡铂，并计划将紫杉醇剂量递增至200和250 mg/m²水平。所有18例患者均已完成治疗。在可评估反应的15例患者中，病理完全缓解率为33%（15例患者中有5例）。在紫杉醇/环磷酰胺诱导序贯周期后给予递增剂量的紫杉醇联合大剂量卡铂导致了显著的非血液学毒性。单周期紫杉醇/环磷酰胺诱导导致了良好的祖细胞动员，并显著改善了该方法的毒性。目前获得的缓解率很有前景，值得进一步评估。
