Paclitaxel administered over 3 h followed by cisplatin in patients with advanced head and neck squamous cell carcinoma: a clinical phase I study.
Paclitaxel administered over 3 h followed by cisplatin in patients with advanced head and neck squamous cell carcinoma: a clinical phase I study.
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对晚期头颈鳞状细胞癌患者给予紫杉醇 3 小时以上，然后给予顺铂：一项临床 I 期研究。
作者：
T. Schilling;B. Heinrich;R. Kau;M. Herzog;S. Quasthoff;K. Diergarten;J. Rastetter;A. Hanauske
我们已经进行了紫杉醇 3 小时输注和顺铂联合治疗的临床 I 期试验，以确定头颈复发或转移性鳞状细胞癌患者的最大耐受剂量和剂量限制毒性。每 21 天重复一次治疗。给药剂量范围为 135 mg/m2 紫杉醇/75 mg/m2 顺铂至 250 mg/m2 紫杉醇/100 mg/m2 顺铂。已有 24 名患者参与了这项研究。最大耐受剂量确定为 225-250 mg/m2 紫杉醇/100 mg/m2 顺铂。该方案的剂量限制性毒性是骨髓抑制（粒细胞减少症）。神经感觉和神经运动毒性为中度。然而，阈值电紧张研究的分析表明大多数患者存在亚临床神经毒性。一名接受 200 mg/m2 紫杉醇/100 mg/m2 顺铂治疗的患者出现 3 级运动神经毒性。 8 名接受 200 mg/m2 紫杉醇/100 mg/m2 顺铂或更高剂量的患者观察到体位性低血压。观察到紫杉醇 175 mg/m2/顺铂 100 mg/m2（n = 5；1 名患者完全缓解）、紫杉醇 200 mg/m2/顺铂 100 mg/m2（n = 3；3 名患者部分缓解）和紫杉醇 225 mg/m2/顺铂 100 mg/m2（n = 8；部分缓解）的客观缓解1 名患者有反应）。另外 11 名患者病情稳定。我们的结论是，紫杉醇输注 3 小时，然后顺铂给药是晚期头颈癌的有效治疗方案，直立性低血压可能是潜在的显着临床毒性。
We have performed a clinical phase I trial of a combination treatment with paclitaxel given as 3-hour infusion and cisplatin to determine the maximum tolerated dose and the dose-limiting toxicity in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Treatment was repeated every 21 days. Doses administered ranged from 135 mg/m2 paclitaxel/75 mg/m2 cisplatin to 250 mg/m2 paclitaxel/100 mg/m2 cisplatin. Twenty-four patients have been entered into this study. The maximum tolerated dose was determined to be 225-250 mg/m2 paclitaxel/100 mg/m2 cisplatin. The dose-limiting toxicity of this regimen was myelosuppression (granulocytopenia). Neurosensory and neuromotor toxicity was moderate. However, analyses of threshold electrotonus studies indicated subclinical neurotoxicity in most patients. One patient receiving 200 mg/m2 paclitaxel/100 mg/m2 cisplatin developed grade 3 motor-neurotoxicity. Orthostatic hypotension was observed in 8 patients receiving doses of 200 mg/m2 paclitaxel/100 mg/m2 cisplatin or higher. Objective responses were observed at paclitaxel 175 mg/m2/ cisplatin 100 mg/m2 (n = 5; complete response in 1 patient), paclitaxel 200 mg/ m2/cisplatin 100 mg/m2 (n = 3; partial response in 3 patients) and at paclitaxel 225 mg/m2/cisplatin 100 mg/m2 (n = 8; partial response in 1 patient). Eleven additional patients had stable disease. We conclude that paclitaxel administered as a 3-hour infusion followed by cisplatin is an active regimen in advanced head and neck cancer and that orthostatic hypotension may be a potentially significant clinical toxicity.