Bokemeyer C, Schmoll H J, Natt F, Knoche M, Beyer J, Souchon R
Hannover University Medical School, Department of Haematology/Oncology, Germany.
J Cancer Res Clin Oncol. 1994;120(12):754-7. doi: 10.1007/BF01194278.
Paclitaxel represents a novel antitumour agent with demonstrated activity in cisplatin-sensitive tumours, particularly ovarian cancer. In addition, responses to paclitaxel have been observed in patients with cisplatin-refractory ovarian cancer. The role of paclitaxel in the treatment of testicular cancer has not been explored so far. Despite the generally high cure rates in patients with metastatic testicular cancer, patients with relapsed disease not responding to platin-based salvage chemotherapy have an extremely poor prognosis. In a phase I/II trial 10 patients with relapsed, cisplatin-refractory malignant germ-cell tumours were treated with paclitaxel as 6-h infusions (8 patients) or 3-h infusions (2 patients) at doses from 135 mg/m2 to 310 mg/m2 at 3-week intervals. Three patients achieved a response to paclitaxel, but disease recurred shortly in two patients after two and four cycles of therapy, respectively. One patient has remained in marker-negative partial response for more than 5 months. The toxicity of paclitaxel was tolerable for a dose range from 135 mg/m2 to 225 mg/m2. Granulocytopenia, WHO grades 3 and 4, occurred in all patients but was of short duration (median 3 days; range: 2-7 days). Other toxicities such as mucositis (5 patients grade 1), neurotoxicity (1 patient grade 1, 2 patients grade 2), infection (1 patient grade 3) and diarrhoea (1 patient grade 2) were not dose-limiting. There were no hypersensitivity reactions, but 1 patient developed severe myalgias during therapy with paclitaxel. Six patients with documented cisplatin-refractory disease were retreated with cisplatin-based chemotherapy after paclitaxel treatment and, in 4 of these, tumour responses of 3, 4, 5 and more than 5 months duration were achieved. In order to explore the role of paclitaxel in relapsed and/or cisplatin-refractory testicular cancer a phase II study using a 3-h infusion of 225 mg/m2 paclitaxel every 3 weeks, conducted by the German Testicular Cancer Study Group, is ongoing.
紫杉醇是一种新型抗肿瘤药物，已证明对顺铂敏感的肿瘤，尤其是卵巢癌有活性。此外，在顺铂难治性卵巢癌患者中也观察到了对紫杉醇的反应。到目前为止，紫杉醇在睾丸癌治疗中的作用尚未得到探索。尽管转移性睾丸癌患者的总体治愈率较高，但对铂类挽救化疗无反应的复发患者预后极差。在一项I/II期试验中，10例复发的、顺铂难治性恶性生殖细胞肿瘤患者接受了紫杉醇治疗，其中8例患者采用6小时输注，2例患者采用3小时输注，剂量为135mg/m²至310mg/m²，每3周一次。3例患者对紫杉醇有反应，但分别在两个和四个周期的治疗后，有2例患者疾病很快复发。1例患者持续5个多月处于标记物阴性的部分缓解状态。紫杉醇的毒性在135mg/m²至225mg/m²的剂量范围内是可耐受的。所有患者均出现3级和4级粒细胞减少，但持续时间较短（中位3天；范围：2 - 7天）。其他毒性如粘膜炎（5例1级）、神经毒性（1例1级，2例2级）、感染（1例3级）和腹泻（1例2级）均未达到剂量限制。未发生过敏反应，但1例患者在紫杉醇治疗期间出现严重肌痛。6例记录为顺铂难治性疾病的患者在紫杉醇治疗后接受了基于顺铂的化疗，其中4例患者实现了持续3、4、5和超过5个月的肿瘤反应。为了探索紫杉醇在复发和/或顺铂难治性睾丸癌中的作用，德国睾丸癌研究组正在进行一项II期研究，每3周静脉输注225mg/m²紫杉醇3小时。
