A network meta-analysis of therapies for previously untreated chronic lymphocytic leukemia
ABSTRACT Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against chlorambucil, but have not been directly compared against each other. There is currently no agreed upon standard therapeutic regimen for treatment-naïve CLL.
We performed a systematic literature review to identify randomized controlled trials (RCTs) published prior to November 2011 of therapies for previously untreated CLL. We conducted a network meta-analysis using fixed and random effect statistical models to estimate differences between shape and scale parameters of progression-free survival (PFS) curves for each competing therapy. We used the parameter estimates and a Weibull distribution to project mean PFS for each therapy option.
Five RCTs were included in our comparison network. Overall, patients were younger (59-65years), had good performance status based on the Eastern Cooperative Oncology Group scale (ECOG 0-1), and earlier stage disease (Rai 0-II or Binet A or B). The combination regimen fludarabine with cyclophosphamide and rituximab (FCR) was estimated to yield mean PFS of 76months (95% CrI: 60, 91), FC 60months (46, 73), fludarabine 38months (27, 49), alemtuzumab 24months (15, 32), and chlorambucil 23months (15, 32).
Our results suggest that FCR has relatively higher potential of preventing disease progression in younger, healthier, treatment-naïve CLL patients and should be considered an optimal initial treatment strategy for this patient population. However, because estimates are based on model simulation, additional studies of FCR are necessary to clinically validate its therapeutic potential.
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ABSTRACT: Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identification of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efficacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL.Oncotarget 12/2013; 5(1). · 6.63 Impact Factor
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ABSTRACT: Background: Few studies have directly compared clinical efficacy and safety among Chinese herb injections (CHIs) for gastric cancer (GC). The present study aimed to compare CHIs combined with FOLFOX regimens for GC to show which provides the best CHIs results. Materials and Methods: 9 electronic databases and 6 gray literature databases were comprehensive searched in April 20, 2013. According to inclusion and exclusion criteria, two reviewers independently selected and assessed the included trials. The risk of bias tool described in the Cochrane Handbook version 5.1.0 and CONSORT statement were used to assess the quality of the trials. All calculations and graphs were performed and produced using ADDIS 1.16.5 software. Results: A total of 541 records were searched and 38 RCTs met the inclusion criteria (2,761 participants), involving 10 CHIs. The results of network meta-analysis showed that compared with FOLFOX alone, combinations with Kanglaite, Astragalus polysaccharides, Cinobufacini, or Yadanziyouru injections could furthest strengthen ORR, improve the quality of life, reduce nausea and vomiting, and reduce the incidence of leukopenia (III-IV). Conclusions: Kanglaite injection, Astragalus polysaccharides injection, Yadanziyouru injection were superior to other CHIs in clinical efficacy and safety for GC. The conclusions now need to be confirmed by large sample size direct head-to-head studies.Asian Pacific journal of cancer prevention: APJCP 06/2014; 15(12):4795-800. DOI:10.7314/APJCP.2014.15.12.4795 · 2.51 Impact Factor
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ABSTRACT: Background: A limited evidence exists regarding comparisons of clinical effectiveness of available therapies for first-line treatment of chronic lymphocytic leukemia (CLL). Methods: We compared available therapies for treatment-naïve, symptomatic CLL regarding progression free survival (PFS) and overall survival (OS) in all the identified random control trials and in subgroups composed of younger/fit and older/unfit patients, using a Bayesian network meta-analysis. Results: In younger/fit patients we obtained median of projected mean PFS of: 19, 26, 31, 43, 51 and 75 months for chlorambucil, fludarabine, alemtuzumab, fludarabine with cyclophosphamide (FC), bendamustine and fludarabine with cyclophosphamide and rituximab (FCR), respectively. We noted median OS of: 59, 66, 66, 70 months for FC, chlorambucil, FCR and fludarabine, respectively. In older/unfit patients we noted PFS of: 16, 17, 24, 30, 60 months for chlorambucil, fludarabine and chlorambucil with ofatumumab (OClb) or rituximab (RClb) or obinutuzumab (GClb), respectively. We obtained median OS of: 44, 58, 59 and 90 months for fludarabine, RClb, chlorambucil and GClb, respectively. Conclusions: Our results suggest that: (1) FCR has higher potential of preventing CLL progression in younger/ fit patients over four therapy options, which were subject of previous meta-analysis but also over bendamustine; (2) in these patients FCR does not entail prolonging of OS in comparison with chlorambucil and it is outperformed by fludarabine; (3) in older/unfit patients GClb demonstrates longer projected PFS than all assessed comparators; (4) in this group GClb has also the highest potential of increasing OS.Cancer Treatment Reviews 02/2015; 41(77-93):http://dx.doi.org/10.1016/j.ctrv.2014.11.004. DOI:10.1016/j.ctrv.2014.11.004 · 6.47 Impact Factor