Motzer R J, Chou T C, Schwartz L, Bosl G J, Bajorin D F, Hutter H
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Semin Oncol. 1995 Jun;22(3 Suppl 6):12-5.
The teratocarcinoma cell line 833K and its relatively cisplatin-resistant subline 833K/63CP 10 were used to assess the cytotoxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), cisplatin, and 4-hydroxyperoxycyclophosphamide quantitatively. The results showed that paclitaxel had marked cytotoxicity against teratocarcinoma, particularly in the cells that were relatively cisplatin resistant. These studies suggested synergy in cytotoxicity for paclitaxel, cisplatin, and 4-hydroxyperoxycyclophosphamide. A phase II trial of paclitaxel was conducted in patients with previously treated germ cell tumors with restricted prior treatment. The paclitaxel dose was 250 mg/m2 given by 24-hour continuous infusion. In 31 patients treated with paclitaxel, eight (26%) achieved a major (complete or partial) response. The antitumor activity of paclitaxel in the phase II trial has led us to further study it as a part of combination therapy. Since the in vitro studies showed synergistic cytotoxicity, combination studies of paclitaxel, ifosfamide, and platinum are under way as salvage treatment for patients with germ cell tumors.
采用畸胎瘤细胞系833K及其相对顺铂耐药的亚系833K/63CP 10定量评估紫杉醇(泰素;百时美施贵宝公司,新泽西州普林斯顿)、顺铂和4-羟基过氧环磷酰胺的细胞毒性。结果显示,紫杉醇对畸胎瘤具有显著的细胞毒性,尤其是对相对顺铂耐药的细胞。这些研究提示紫杉醇、顺铂和4-羟基过氧环磷酰胺在细胞毒性方面具有协同作用。对既往治疗过且既往治疗受限的生殖细胞肿瘤患者进行了紫杉醇的II期试验。紫杉醇剂量为250 mg/m²,通过24小时持续输注给药。在31例接受紫杉醇治疗的患者中,8例(26%)获得主要(完全或部分)缓解。紫杉醇在II期试验中的抗肿瘤活性促使我们将其作为联合治疗的一部分进行进一步研究。由于体外研究显示出协同细胞毒性,目前正在进行紫杉醇、异环磷酰胺和铂类的联合研究,作为生殖细胞肿瘤患者的挽救治疗。