Single-agent purine analogues for the treatment of chronic lymphocytic leukaemia: A systematic review and meta-analysis

Steurer, Michael; Pall, Georg; Richards, Sue; Schwarzer, Guido; Bohlius, Julia; Greil, Richard

doi:10.1016/j.ctrv.2006.05.002

Cited by 57 publications

(28 citation statements)

References 24 publications

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“…[1][2][3][4][5] This has been confirmed by different meta-analyses. 29,30 Moreover, the results emphasize the need for further phase III trials for comorbid patients to determine the role of novel treatment modalities in this patient population, especially of chemoimmunotherapy regimens. 28 These studies should include concepts for supportive care, an assessment of the quality of life, and recommendations for second-line therapies, which seem to be or primordial importance in this group of patients.…”

Section: Discussionmentioning

confidence: 99%

First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

Eichhorst

Busch²,

Stilgenbauer

et al. 2009

Blood

293

163

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Section: Discussionmentioning

confidence: 99%

First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

Eichhorst

Busch²,

Stilgenbauer

et al. 2009

Blood

293

163

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“…The availability of effective treatments subsequent to disease progression therefore plays an important role in the association between endpoints, because a long post-progression period adds randomness that attenuates the ability to detect os benefits. In the context of cll, studies in previously untreated patients receiving a first-line treatment often show a statistically significant improvement of pfs, but not of os 37,[41][42][43][44][45][46][47][48] . In fact, in studies assessing first-line treatment, the time from first therapy to final endpoint is often long enough to introduce confounding factors such as crossover and subsequent-line therapies, leading to a statistically nonsignificant difference in os.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Progression-Free Survival and Overall Survival in Chronic Lymphocytic Leukemia: A Literature-Based Analysis

et al. 2015

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“…A Cochrane Review based on published trial data was also not able to detect any overall survival benefit but a significant degree of heterogeneity was found. 2,3 To overcome the limitations of meta-analyzing data derived from published trials, a collaborative IPD analysis was conducted integrating individual patient data from all trials to examine whether, with larger patient numbers available, any clinically worthwhile survival differences could be detected, and whether apparently discrepant trial results might be, at least partially, explained by variations in analytical methods.…”

Section: Discussionmentioning

confidence: 99%

“…1 In 2006, a Cochrane Collaboration systematic review of single-agent purine analogs compared with alkylating agents was published. 2,3 This review used published data and included results from 5 trials but identified one other trial for which results could not be extracted from publications, and 3 more that had only recently closed. The primary end points in these trials varied from response to survival or progression free survival (PFS), and all three measures were analyzed in the review.…”

Section: Introductionmentioning

confidence: 99%

Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials

Richards

Steurer²

2011

Haematologica

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All randomized trials of active treatment comparisons in untreated CLL which involved at least one treatment arm including a purine analog, and which began in 2004 or before, were included, with the exception of those involving an antibody therapy, such as rituximab or alemtuzumab.The Clinical Trial Service Unit has established a database of randomized trials in leukemia, identified by periodic searches of electronic databases including MEDLINE, EMBASE, meeting abstracts and clinical trial registration databases. For this review, additional review August 15, 2011. Revised version arrived on October 10, 2011. Manuscript accepted on October 24, 2011 A systematic review of purine analogs revealed heterogeneity between trials in treatment effects on response and progression free survival, but not survival, perhaps partly due to variations in analytical methods. In addition, combination treatments required evaluation. Therefore, individual patient data were sought for all randomized trials in untreated chronic lymphocytic leukemia which involved a purine analog, but which did not include antibody therapies. Sixteen trials were found, addressing seven comparisons. Eight trials, with 2,753 patients, showed that single agent purine analog improved progression free survival (odds ratio=0.71; 95% confidence interval=0.63-0.79). Heterogeneity remained substantial. Three trials, with 1,403 patients, showed that progression free survival was further improved by the addition of cyclophosphamide (odds ratio=0.54; 0.47-0.62). Fewer data were available on the addition of other drugs to purine analog, and none showed clear benefit. Two trials, with 544 patients, suggested cladribine improved progression free survival compared to fludarabine (odds ratio=0.77; 0.63-0.95). No differences were seen in overall survival for any comparisons. In conclusion, purine analogs, particularly combined with cyclophosphamide, significantly improve progression free survival but not survival. Some groups, such as the elderly, may not see the same benefits and maximizing doses may be important for all treatments, including chlorambucil. Longer follow up, consistent definitions and detailed reporting of trials should be encouraged. 428-436. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACTarticles, meeting abstracts (ASH, EHA, IWCLL) and reference lists of published trials were hand searched. Principal investigators from the identified trials were invited to join the collaborative group, to provide preliminary data, and to attend a meeting in 2007 at which preliminary results were presented (Online Supplementary Appendix). These, and other experts in the field, were consulted to ensure completeness of the list of relevant trials.Information on each trial was sought from protocols, publications and the trialists themselves. As well as details of eligibility criteria and treatments (including duration and protocol defined crossovers), methods of randomization, definition and timing of response assessments, definition of disease progre...

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Single-agent purine analogues for the treatment of chronic lymphocytic leukaemia: A systematic review and meta-analysis

Cited by 57 publications

References 24 publications

First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

Relationship between Progression-Free Survival and Overall Survival in Chronic Lymphocytic Leukemia: A Literature-Based Analysis

Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials

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