Comer A M, Goa K L
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs Aging. 2000 Jul;17(1):53-80. doi: 10.2165/00002512-200017010-00004.
Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). In noncomparative trials in patients with NSCLC, docetaxel 75 or 100 mg/m2 produced objective response rates of 20 to 38% and 14 to 25% as a first-line or second-line monotherapy, respectively. In Japan, docetaxel 60 mg/m2 produced objective response rates of 19 to 25% in previously untreated patients. Docetaxel 100 or 75 mg/m2 produced significantly higher response rates than either vinorelbine or ifosfamide in previously treated patients; patients treated with docetaxel 75 mg/m2 had an improved 1-year survival rate compared with those who received vinorelbine or ifosfamide. Docetaxel monotherapy in chemotherapy-naive patients produced survival rates that are similar to those reported for most platinum-containing standard combinations such as cisplatin plus vinorelbine. Combination of docetaxel with one other antineoplastic resulted in objective response rates of 20 to 54% in chemotherapy-naive patients; triple chemotherapy combinations produced responses in 51 and 60% of patients. Promising results from a few small studies and one large phase II study have also indicated a potential role for docetaxel as neoadjuvant therapy. The main dose-limiting adverse event associated with docetaxel is neutropenia, and fluid retention is common in many patients. The tolerability profile is generally acceptable in the majority of patients, although extra care has to be taken in patients with impaired liver function to minimise the risk of severe or febrile neutropenia. Conclusions. Docetaxel is generally well tolerated by patients receiving treatment for locally advanced and metastatic NSCLC, and produces response and survival rates equivalent to many current standard treatment options. Comparative studies have shown that docetaxel monotherapy provides significant survival benefits over best supportive care or treatment with vinorelbine or ifosfamide. Response and 1-year survival rates with docetaxel monotherapy are particularly encouraging in patients refractory or resistant to cisplatin or carboplatin, for whom treatment options are few. Neoadjuvant docetaxel has produced improved survival compared with local treatment alone. Combinations of docetaxel with other antineoplastic agents have produced relatively high response and 1-year survival rates; however, further comparative studies are required to confirm these benefits. In the meantime, docetaxel is a welcome addition to the options available for patients with advanced NSCLC.
多西他赛是紫杉烷类抗肿瘤药物中的一种半合成药物,对局部晚期和转移性非小细胞肺癌(NSCLC)患者的治疗有效。在NSCLC患者的非对照试验中,多西他赛75或100mg/m²作为一线或二线单药治疗时,客观缓解率分别为20%至38%和14%至25%。在日本,多西他赛60mg/m²在既往未治疗的患者中产生的客观缓解率为19%至25%。在既往接受过治疗的患者中,多西他赛100或75mg/m²产生的缓解率显著高于长春瑞滨或异环磷酰胺;接受多西他赛75mg/m²治疗的患者与接受长春瑞滨或异环磷酰胺治疗的患者相比,1年生存率有所提高。在未接受过化疗的患者中,多西他赛单药治疗产生的生存率与大多数含铂标准联合方案(如顺铂加长春瑞滨)报道的生存率相似。多西他赛与另一种抗肿瘤药物联合使用,在未接受过化疗的患者中客观缓解率为20%至54%;三联化疗方案在51%和60%的患者中产生缓解。一些小型研究和一项大型II期研究的有前景结果也表明多西他赛作为新辅助治疗具有潜在作用。与多西他赛相关的主要剂量限制性不良事件是中性粒细胞减少,许多患者常见液体潴留。尽管对于肝功能受损的患者必须格外小心以尽量降低严重或发热性中性粒细胞减少的风险,但在大多数患者中耐受性一般是可接受的。结论。多西他赛对于接受局部晚期和转移性NSCLC治疗的患者一般耐受性良好,并产生与许多当前标准治疗方案相当的缓解率和生存率。比较研究表明,多西他赛单药治疗比最佳支持治疗或长春瑞滨或异环磷酰胺治疗具有显著的生存获益。对于对顺铂或卡铂难治或耐药且治疗选择有限的患者,多西他赛单药治疗的缓解率和1年生存率尤其令人鼓舞。与单纯局部治疗相比,新辅助多西他赛可提高生存率。多西他赛与其他抗肿瘤药物联合使用产生了相对较高的缓解率和1年生存率;然而,需要进一步的比较研究来证实这些获益。与此同时,多西他赛是晚期NSCLC患者可用治疗选择中的一个受欢迎的补充。