Donato M L, Gershenson D M, Wharton J T, Ippoliti C M, Aleman A S, Bodurka-Bevers D, Bevers M W, Burke T W, Levenback C F, Wolf J K, Freedman R S, Bast R C, Gajewski J L, Champlin R E
Department of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gynecol Oncol. 2001 Sep;82(3):420-6. doi: 10.1006/gyno.2001.6326.
The goal of this study was to determine the optimal dose of topotecan when used in combination with high-dose melphalan and cyclophosphamide (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer.
Fifty-three patients with persistent or recurrent ovarian cancer were treated. Disease status at study entry included: platinum-sensitive recurrent disease (15 patients), platinum-resistant or refractory recurrent disease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m(2)/day on Days -6, -5, -4; melphalan 70 mg/m(2)/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m(2)/day on Days -6 to -2. Peripheral blood stem cells were infused on Day 0.
The optimal topotecan dose selected for future trials was 4.0 mg/m(2)/day x 5 days. The regimen had acceptable toxicity with no regimen-related death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with measurable or evaluable disease was 93%. Median survival has not yet been reached, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive.
With a topotecan dose of 4.0 mg/m(2)/day x 5 days, the TMC regimen has acceptable toxicity and produces high response rates. In the setting of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian cancer.
本研究的目的是确定拓扑替康与大剂量美法仑和环磷酰胺联合使用（TMC）时的最佳剂量，并评估该方案对晚期卵巢癌患者的毒性和疗效。
对53例持续性或复发性卵巢癌患者进行了治疗。研究入组时的疾病状态包括：铂敏感复发性疾病（15例）、铂耐药或难治性复发性疾病（15例）、二次探查手术阳性（16例）、未达到初次临床完全缓解（CR）（7例）。在干细胞动员和采集后，患者在第-6、-5、-4天接受环磷酰胺1 g/m²/天；在第-3、-2天接受美法仑70 mg/m²/天；在第-6至-2天接受拓扑替康，剂量从1.25 mg/m²/天递增至4.0 mg/m²/天。外周血干细胞在第0天输注。
为未来试验选择的最佳拓扑替康剂量为4.0 mg/m²/天×5天。该方案具有可接受的毒性，无与方案相关的死亡。毒性（Bearman毒性标准）主要局限于1-2级粘膜炎和腹泻。可测量或可评估疾病患者的总体缓解率为93%。中位生存期尚未达到，但中位随访18个月（范围：11-37个月），77%的患者存活。
拓扑替康剂量为4.0 mg/m²/天×5天时，TMC方案具有可接受的毒性并产生高缓解率。在卵巢癌的情况下，大剂量化疗应仅作为精心设计的临床试验的一部分进行。TMC应被视为晚期卵巢癌患者未来随机试验的潜在方案。
