Docetaxel and irinotecan, alone and in combination, in the treatment of non-small cell lung cancer.
Docetaxel and irinotecan, alone and in combination, in the treatment of non-small cell lung cancer.
复制标题
多西他赛和伊立替康单独或联合治疗非小细胞肺癌。
作者：
A. Adjei;A. Argiris;J. Murren
多西他赛和伊立替康在几种实体瘤（包括非小细胞肺癌（NSCLC））中均观察到单药活性。对多西他赛单药治疗NSCLC的II期临床试验的数据进行汇总，得出的总体缓解率为26%，1年生存率为52%。此外，最近一项联合放疗和同步多西他赛治疗的研究报告了77%的总体缓解率。多西他赛治疗最重要的不良反应是中性粒细胞减少，伊立替康单药治疗NSCLC患者的II期试验的缓解率为15%-31%。主要毒副反应为中性粒细胞减少和腹泻。研究者已经开始探索多西他赛和伊立替康联合治疗的疗效。临床前研究的结果表明，给药的时间表和顺序可能很重要。一项日本研究在既往未经治疗的NSCLC患者中评估了该组合，并在26名患者（32%）中发现了8例部分缓解。最近在马约诊所进行的一项I期研究显示，在接受伊立替康后接受多西他赛治疗的5例患者中，有3例出现部分缓解。在耶鲁癌症中心进行的一项I期研究中，在伊立替康（50 mg/m2）给药前给予递增剂量的多西他赛（25 - 40 mg/m2），持续4周，随后停药2周。在5例可评价的NSCLC患者中有1例部分缓解（4例既往未接受过化疗的患者中有1例）。这些研究的结果表明，多西他赛和伊立替康联合治疗NSCLC显示出前景。伊立替康也与其他化疗药物联合使用。伊立替康/依托泊苷联合治疗的评价不太广泛，但迄今为止似乎与相当大的毒性相关，特别是骨髓抑制，没有明确的治疗优势。1份使用伊立替康/顺铂/依托泊苷三联治疗的报告导致42例NSCLC患者（38%）中的16例部分缓解。与多西他赛一样，伊立替康已有效地与放射治疗联合使用，在一些研究中部分缓解率超过70%。
Single-agent activity has been observed for both docetaxel and irinotecan in several solid tumors, including non-small cell lung cancer (NSCLC). Compilation of data from phase II trials of single-agent docetaxel therapy in NSCLC yielded overall response rates of 26% and a 1-year survival rate of 52%. Furthermore, a recent study that combined radiotherapy with concurrent docetaxel treatment reported an overall response rate of 77%. The most important adverse effect of docetaxel therapy is neutropenia Phase II trials of single-agent irinotecan for NSCLC patients resulted in response rates of 15% to 31%. The main toxicities were neutropenia and diarrhea. Investigators have begun to explore the efficacy of combining docetaxel and irinotecan. The results of preclinical studies suggest that schedule and order of administration may be important. A Japanese study evaluated the combination in previously untreated patients with NSCLC, and found eight partial responses in 26 patients (32%). A recent phase I study at the Mayo Clinic showed partial responses in three of five patients who received irinotecan followed by docetaxel. In a phase I study conducted at Yale Cancer Center, escalating doses of docetaxel (25 to 40 mg/m2) were given before irinotecan (50 mg/m2) for 4 weeks followed by a 2-week rest. There was one partial response among five evaluable patients with NSCLC (one of four among patients who had received no prior chemotherapy). The results of these studies suggest that the combination of docetaxel and irinotecan shows promise in the treatment of NSCLC. Irinotecan also has been used in combination with other chemotherapeutic agents. The irinotecan/etoposide combination has been less extensively evaluated but thus far appears to be associated with considerable toxicity, particularly myelosuppression, without clear therapeutic advantage. One report of the use of the triple combination of irinotecan/cisplatin/etoposide resulted in 16 partial responses in 42 NSCLC patients (38%). Like docetaxel, irinotecan has been used effectively in conjunction with radiation therapy, with partial response rates in some studies of more than 70%.