Download PDF
J Neurol Surg B Skull Base 2022; 83(02): 210-214
DOI: 10.1055/s-0040-1718766
Original Article

The Efficacy of Adjuvant Chloroquine for Glioblastoma: A Meta-Analysis of Randomized Controlled Studies

Hong Wei
1   Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Liaoning, China
,
Zhenfu Jiang
2   Department of Neurosurgery, The Second Hospital of Dalian Medical University, Liaoning, China
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Introduction The efficacy of adjuvant chloroquine for glioblastoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence of adjuvant chloroquine on treatment efficacy for recurrent glioblastoma.

Methods We search PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through January 2020 for randomized controlled trials (RCTs) assessing the efficacy of adjuvant chloroquine for glioblastoma. This meta-analysis is performed using the random-effect model.

Results Three RCTs are included in the meta-analysis. Overall, compared with control group for glioblastoma, adjuvant chloroquine is associated with significantly reduced mortality (risk ratio [RR] = 0.59; 95% confidence interval [CI] = 0.47–0.72; p < 0.00001), improved remission (RR = 11.53; 95% CI = 1.53–86.57; p = 0.02), and prolonged survival time (Std.MD = 11.53; 95% CI = 1.53–86.57; p = 0.02), but has no substantial effect on recurrence (RR = 0.42; 95% CI = 0.12–1.49; p = 0.18).

Conclusion Adjuvant chloroquine may provide additional benefits for the treatment of glioblastoma.

Keywords

chloroquine - glioblastoma - efficacy - randomized controlled trials


Publication History

Received: 09 March 2020

Accepted: 19 August 2020

Article published online:
11 May 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Clarke J, Butowski N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol 2010; 67 (03) 279-283
    CrossrefPubMedGoogle Scholar
  • 2 Wang J, Shen F, Yao Y, Wang LL, Zhu Y, Hu J. Adoptive cell therapy: a novel and potential immunotherapy for glioblastoma. Front Oncol 2020; 10: 59
    CrossrefPubMedGoogle Scholar
  • 3 van der Louw EJTM, Olieman JF, van den Bemt PMLA. et al. Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study. Ther Adv Med Oncol 2019; 11: 1758835919853958
    CrossrefPubMedGoogle Scholar
  • 4 Sotelo J, Briceño E, López-González MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2006; 144 (05) 337-343
    CrossrefPubMedGoogle Scholar
  • 5 Ji X, Zhu H, Dai X. et al. Overexpression of GBP1 predicts poor prognosis and promotes tumor growth in human glioblastoma multiforme. Cancer Biomark 2019; 25 (03) 275-290
    CrossrefPubMedGoogle Scholar
  • 6 Dong Q, Li Q, Wang M. et al. Elevated CD44 expression predicts poor prognosis in patients with low-grade glioma. Oncol Lett 2019; 18 (04) 3698-3704
    PubMedGoogle Scholar
  • 7 Stupp R, Mason WP, van den Bent MJ. et al; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10) 987-996
    CrossrefPubMedGoogle Scholar
  • 8 Gilbert MR, Wang M, Aldape KD. et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol 2013; 31 (32) 4085-4091
    CrossrefPubMedGoogle Scholar
  • 9 Souhami L, Seiferheld W, Brachman D. et al. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys 2004; 60 (03) 853-860
    CrossrefPubMedGoogle Scholar
  • 10 Grossman SA, Batara JF. Current Management of Glioblastoma Multiforme, Seminars in Oncology. Elsevier; 2004: 635-644
    Google Scholar
  • 11 Briceño E, Reyes S, Sotelo J. Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine. Neurosurg Focus 2003; 14 (02) e3
    CrossrefPubMedGoogle Scholar
  • 12 Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases?. Lancet Infect Dis 2003; 3 (11) 722-727
    CrossrefPubMedGoogle Scholar
  • 13 Reyes S, Herrera LA, Ostrosky P, Sotelo J. Quinacrine enhances carmustine therapy of experimental rat glioma. Neurosurgery 2001; 49 (04) 969-973
    PubMedGoogle Scholar
  • 14 Jia-ming C. Clinical observation of chloroquine treatment for glioma. Ann Intern Med 2011; 17 (12) 1900-1901
    PubMedGoogle Scholar
  • 15 Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535
    CrossrefPubMedGoogle Scholar
  • 16 G. HigginsJPT, Cochrane handbook for systematic reviews of interventions version 5.1. 0 [updated March 2011], The Cochrane collaboration 2011
    PubMed
  • 17 Jadad AR, Moore RA, Carroll D. et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996; 17 (01) 1-12
    CrossrefPubMedGoogle Scholar
  • 18 Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001; 135 (11) 982-989
    CrossrefPubMedGoogle Scholar
  • 19 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21 (11) 1539-1558
    CrossrefPubMedGoogle Scholar
  • 20 Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. Cancer stem cells in glioblastoma. Genes Dev 2015; 29 (12) 1203-1217
    CrossrefPubMedGoogle Scholar
  • 21 Wang J, Cazzato E, Ladewig E. et al. Clonal evolution of glioblastoma under therapy. Nat Genet 2016; 48 (07) 768-776
    CrossrefPubMedGoogle Scholar
  • 22 Qian Z, Ren L, Wu D. et al. Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis. Int J Cancer 2017; 140 (12) 2792-2804
    CrossrefPubMedGoogle Scholar
  • 23 Wasserfallen JB, Ostermann S, Pica A. et al. Can we afford to add chemotherapy to radiotherapy for glioblastoma multiforme? Cost-identification analysis of concomitant and adjuvant treatment with temozolomide until patient death. Cancer 2004; 101 (09) 2098-2105
    CrossrefPubMedGoogle Scholar
  • 24 Lopez-Gonzalez MA, Sotelo J. Brain tumors in Mexico: characteristics and prognosis of glioblastoma. Surg Neurol 2000; 53 (02) 157-162
    CrossrefPubMedGoogle Scholar
  • 25 Wong ET, Hess KR, Gleason MJ. et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 1999; 17 (08) 2572-2578
    CrossrefPubMedGoogle Scholar
  • 26 Duerinck J, Du Four S, Bouttens F. et al. Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma. J Neurooncol 2018; 136 (01) 115-125
    CrossrefPubMedGoogle Scholar
  • 27 Jensen PB, Sørensen BS, Sehested M, Grue P, Demant EJ, Hansen HH. Targeting the cytotoxicity of topoisomerase II-directed epipodophyllotoxins to tumor cells in acidic environments. Cancer Res 1994; 54 (11) 2959-2963
    PubMedGoogle Scholar
  • 28 Pozzi D, Zompetta C, Faggioni A. et al. Early events of fusion between Epstein Barr virus and human lymphoblastoid cells (Raji) detected by R18 fluorescence dequenching measurements. Membr Biochem 1990; 9 (04) 239-251
    CrossrefPubMedGoogle Scholar
  • 29 Inaba M, Maruyama E. Reversal of resistance to vincristine in P388 leukemia by various polycyclic clinical drugs, with a special emphasis on quinacrine. Cancer Res 1988; 48 (08) 2064-2067
    PubMedGoogle Scholar