Hilkens P H, Pronk L C, Verweij J, Vecht C J, van Putten W L, van den Bent M J
Department of Neuro-Oncology, Dr Daniel den Hoed Cancer Center and University Hospital, Rotterdam, The Netherlands.
Br J Cancer. 1997;75(3):417-22. doi: 10.1038/bjc.1997.68.
Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses.
多西他赛是一种新型半合成紫杉烷类药物,作为一种抗肿瘤药物已显示出有前景的活性。在一项剂量递增研究中,多西他赛与顺铂联合应用于63例患者。由于已知这两种药物都有潜在的神经毒性,因此对周围神经毒性进行了前瞻性详细评估。通过临床体征和症状的总分以及振动觉阈值(VPT)测量来评估神经病变。根据美国国立癌症研究所的“常见毒性标准”对神经病变的严重程度进行分级。在55例可评估患者中,多西他赛-顺铂联合化疗导致29例(53%)出现主要为感觉性神经病变。当顺铂和多西他赛的累积剂量均超过200 mg m(-2)时,35例患者中有26例(74%)出现神经病变,其中15例为轻度,10例为中度,1例为重度。多西他赛和顺铂的累积剂量与治疗后神经病变总分(P < 0.01)以及治疗后VPT(P < 0.01)之间均存在显著相关性。在相似剂量下,这种联合用药的神经毒性作用比顺铂或多西他赛单药更严重。