Di Cosimo Serena, Ferretti Gianluigi, Fazio Nicola, Silvestris Nicola, Carlini Paolo, Alimonti Andrea, Gelibter Alain, Felici Alessandra, Papaldo Paola, Cognetti Francesco
Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy.
Acta Oncol. 2003;42(7):693-700. doi: 10.1080/02841860310011014.
The aim was to investigate the activity of docetaxel in advanced gastric cancer either as single agent or in combination with other drugs. A systematic review was carried out using the databases of Medline, Embase and CancerLit. Results from ASCO and ESMO meetings during 2002 were also included. Eight phase II trials focused on docetaxel as a single agent. Considering collectively the 262 evaluable patients enrolled in these studies, the mean response rate (RR) was 19% (CI 95% 14-24%). Docetaxel was well tolerated with a dose-limiting myelosuppression (grade 3-4 neutropenia in 36-95% of cases). Adding fluorouracil, an RR ranging from 22% to 86% was registered, due to differences in populations studied (young vs elderly) and modalities of drug administration (continuous vs. bolus infusion). RRs for docetaxel-cisplatin combination were 56%, 37% and 36% in three phase II trials and 35% in a phase III trial. The addition of both cisplatin and fluorouracil to docetaxel did not increase toxicity. Randomized trials comparing docetaxel-cisplatin-fluorouracil with ciplatin-fluorouoracil or epirubicin-cisplatin-fluorouracil, the most commonly used regimens, are ongoing. The future results of the above phase III studies could indicate docetaxel as a key drug to improve treatment of patients with advanced gastric cancer.
目的是研究多西他赛在晚期胃癌中作为单药或与其他药物联合使用时的活性。使用Medline、Embase和CancerLit数据库进行了系统评价。2002年美国临床肿瘤学会(ASCO)和欧洲肿瘤内科学会(ESMO)会议的结果也被纳入。八项II期试验聚焦于多西他赛单药治疗。综合考虑这些研究中纳入的262例可评估患者,平均缓解率(RR)为19%(95%置信区间14%-24%)。多西他赛耐受性良好,剂量限制性毒性为骨髓抑制(36%-95%的病例出现3-4级中性粒细胞减少)。添加氟尿嘧啶后,由于研究人群(年轻人与老年人)和给药方式(持续输注与推注)的差异,RR范围为22%至86%。在三项II期试验中,多西他赛-顺铂联合方案的RR分别为56%、37%和36%,在一项III期试验中为35%。在多西他赛中添加顺铂和氟尿嘧啶均未增加毒性。比较多西他赛-顺铂-氟尿嘧啶与顺铂-氟尿嘧啶或表柔比星-顺铂-氟尿嘧啶(最常用方案)的随机试验正在进行。上述III期研究的未来结果可能表明多西他赛是改善晚期胃癌患者治疗的关键药物。