Steurer Michael, Pall Georg, Richards Sue, Schwarzer Guido, Bohlius Julia, Greil Richard
Innsbruck Medical University, Division of Hematology and Oncology, Anichstrasse 35, A-6020 Innsbruck, Austria.
Cancer Treat Rev. 2006 Aug;32(5):377-89. doi: 10.1016/j.ctrv.2006.05.002. Epub 2006 Jun 21.
Recent trials suggest improved response rates for purine analogues compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a survival advantage. Thus, a systematic Cochrane review may be able to further define the role of purine analogues in the first-line treatment of B-CLL.
Randomized controlled trials comparing single-agent purine analogues with alkylator-based regimens were included. Medical databases (Cochrane Library, MEDLINE, EMBASE), conference proceedings and trial registers were searched. We included full-text and abstract publications as well as unpublished data. Relative risks (RR) and hazard ratios (HR) were calculated under a fixed-effects model, clinical and statistical heterogeneity was examined with sensitivity analyses and meta-regression. If applicable, numbers needed to treat or harm (NNT, NNH) were also determined.
Five trials with 1838 randomized patients were included. Importantly, four trials had a cross-over design. There was a trend for improved overall survival for patients receiving purine analogues as initial therapy but statistical significance was just not reached (HR 0.89 [95% CI 0.78-1.01]). The RR for achieving an overall (RR 1.22 [95% CI 1.13-1.31]; NNT 8 [95% CI 6-13]) and complete response (RR 1.94 [95% CI 1.65-2.28]; NNT 6 [5-8]) was significantly improved, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61-0.82]). Incidence of grade III/IV infections (RR 1.83 [95% CI 1.30-2.58]; NNH 20 [95% CI 12.5-50]) and haemolytic anaemia (RR 3.36 [95% CI 1.27-8.91]; NNH 21 [95% CI 6-185]) was significantly higher in patients receiving purine analogues.
Despite significantly increased response rates and longer progression-free survival with purine analogues as first-line therapy, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine analogues augments the risk for grade III/IV infections and haemolytic anaemia.
近期试验表明，在B细胞慢性淋巴细胞白血病（B-CLL）治疗中，与基于烷化剂的治疗方案相比，嘌呤类似物的缓解率有所提高。然而，尚无试验能够显示出其生存优势。因此，Cochrane系统评价或许能够进一步明确嘌呤类似物在B-CLL一线治疗中的作用。
纳入比较单药嘌呤类似物与基于烷化剂治疗方案的随机对照试验。检索医学数据库（Cochrane图书馆、MEDLINE、EMBASE）、会议论文集及试验注册库。纳入全文和摘要出版物以及未发表的数据。在固定效应模型下计算相对风险（RR）和风险比（HR），通过敏感性分析和Meta回归检验临床和统计学异质性。若适用，还确定治疗所需人数或伤害所需人数（NNT, NNH）。
纳入5项试验，共1838例随机分组患者。重要的是，4项试验采用交叉设计。接受嘌呤类似物作为初始治疗的患者总生存有改善趋势，但未达到统计学显著性（HR 0.89 [95% CI 0.78 - 1.01]）。实现总体缓解（RR 1.22 [95% CI 1.13 - 1.31]；NNT 8 [95% CI 6 - 13]）和完全缓解（RR 1.94 [95% CI 1.65 - 2.28]；NNT 6 [5 - 8]）的RR显著改善，从而使无进展生存期延长（HR 0.70 [95% CI 0.61 - 0.82]）。接受嘌呤类似物治疗的患者III/IV级感染发生率（RR 1.83 [95% CI 1.30 - 2.58]；NNH 20 [95% CI 12.5 - 50]）和溶血性贫血发生率（RR 3.36 [95% CI 1.27 - 8.91]；NNH 21 [95% CI 6 - 185]）显著更高。
尽管嘌呤类似物作为一线治疗可显著提高缓解率并延长无进展生存期，但与基于烷化剂的治疗方案相比，我们未能检测到总生存有统计学显著性改善。此外，使用嘌呤类似物会增加III/IV级感染和溶血性贫血的风险。
