:: Volume 20, Issue 4 (10-2022) ::
Int J Radiat Res 2022, 20(4): 809-813 Back to browse issues page
Concurrent administration of Hydroxychloroquine and whole brain radiation therapy for patients with brain metastases
F. Farhan , S. Mansouri , F. Samiee , A. Kazemian , B. Kalaghchi , M. Lashkari , H. Alizadeh , M. Yamrali
Radiation Oncology Research Center (RORC), Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran , maisa36@yahoo.com
Abstract:   (730 Views)
Background: The main purpose of the present study was to evaluate the safety and efficiency of concurrent administration of hydroxychloroquine (HCQ) and whole brain radiation therapy (WBRT) in patients with brain metastases. Based on numerous preclinical reports, inhibition of autophagy by HCQ can significantly enhance the efficacy of DNA-damaging therapies improving results of radiation therapy. The primary end point of this study was response to treatment and complications, determined by the National Cancer Institute Common Toxic Criteria for Adverse Events (CTCAE) scale V5.0. Material and Methods: Patients with pathologically-confirmed primary solid malignancies together with single or multiple brain metastases on magnetic resonance imaging (MRI) were enrolled in the study (n=64). Treatment with HCQ (200 mg/P.O. once daily) was begun concurrent with WBRT (total dose of 30 Grays (Gy) in 10 daily fractions) in case group. Control group received the standard regimen. Results: Analysis of complications and response rate at each follow up points revealed no statistically significant differences between the case and control groups. Although, median brain metastasis specific Progression Free Survival (PFS) was non-significantly longer in HCQ group compared to control. No grade 3 or more severe toxicities were reported during therapy in both groups of the study. Conclusion: Although concurrent administration of HCQ with WBRT in patients who suffers from brain metastases was well tolerated, this combination did not meaningfully improve outcomes in comparison to WBRT alone.
 
 
Keywords: Whole brain radiation therapy, hydroxychloroquine, brain metastases, autophagy, radio-sensitizers.
Full-Text [PDF 658 kb]   (394 Downloads)    
Type of Study: Original Research | Subject: Radiation Biology
References
1. 1. Achrol A, Rennert R, Anders C, Soffietti R, S. Ahluwalia M, Nayak L, et al. (2019) Brain metastases. Nat Rev Dis Primers, 5: 5. [DOI:10.1038/s41572-018-0055-y] [PMID]
2. van den Bent M (2003) The role of chemotherapy in brain metastases. Eur J Cancer, 39: 2114-2120. [DOI:10.1016/S0959-8049(03)00577-X] [PMID]
3. Gremmer R, Schröder M, ten Huinink W, Brandsma D, Boogerd W (2008) Successful management of brain metastasis from malignant germ cell tumours with standard induction chemotherapy. J Neurooncol, 90: 335-339. [DOI:10.1007/s11060-008-9668-4] [PMID]
4. Goldstein D and Berkowitz R (2012) Current management of gestational trophoblastic neoplasia. Hematol Oncol Clin North Am, 26: 111-131. [DOI:10.1016/j.hoc.2011.10.007] [PMID]
5. Chao J, Phillips R, Nickson J (1954) Roentgen-ray therapy of cerebral metastases. Cancer, 7: 682-689 https://doi.org/10.1002/1097-0142(195407)7:4<682::AID-CNCR2820070409>3.0.CO;2-S [DOI:10.1002/1097-0142(195407)7:43.0.CO;2-S] [PMID]
6. Andrews D, Scott C, Sperduto P, et al. (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet, 363: 1665-1672. [DOI:10.1016/S0140-6736(04)16250-8] [PMID]
7. Bezjak A, Adam J, Panzarella T, Levin W, Barton R, Kirkbride P, et al. (2001) Radiotherapy for brain metastases: defining palliative response. Radiother Oncol, 61: 71-76. [DOI:10.1016/S0167-8140(01)00426-1] [PMID]
8. Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. (1997) Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys, 37: 745-751 [DOI:10.1016/S0360-3016(96)00619-0] [PMID]
9. Kim E, Wustenberg R, Rubsam A, Schmitz-Salue C, Warnecke G, Bücker E, et al. (2010) Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells. Neuro-Oncology, 12: 389-40010. [DOI:10.1093/neuonc/nop046] [PMID] []
10. Briceño E, Calderon A, Sotelo J (2007) Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme. Surg Neurol, 67: 388-391. [DOI:10.1016/j.surneu.2006.08.080] [PMID]
11. Sotelo J, Briceño E, López-González M (2006) Adding chloroquine to conventional treatment for glioblastoma multiforme. Ann Intern Med, 144: 337. [DOI:10.7326/0003-4819-144-5-200603070-00008] [PMID]
12. Marmor M, Kellner U, Lai T, Lyons J, Mieler W (2011) Revised Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy Ophthalmol, 118: 415-422. [DOI:10.1016/j.ophtha.2010.11.017] [PMID]
13. Freites-Martinez A, Santana N, Arias-Santiago S, Viera A (2021) Using the common terminology criteria for adverse events (CTCAE - Version 5.0) to evaluate the severity of adverse events of anticancer therapies. (English Edition) Actas Dermosifiliogr, 112: 90-92. https://doi.org/10.1016/j.ad.2019.05.009 [DOI:10.1016/j.adengl.2019.05.021] [PMID]
14. Borgelt B, Gelber R, Larson M, Hendrickson F, Griffin T, Roth R (1981) Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: Final results of the first two studies by the radiation therapy oncology group. Int J Radiat Oncol Biol Phys, 7: 1633-1638. https://doi.org/10.1016/0360-3016(81)90370-9 [DOI:10.1016/0360-3016(81)90184-X]
15. Davey P, Hoegler D, Ennis M, Smith J (2008) A phase III study of accelerated versus conventional hypofractionated whole brain irradiation in patients of good performance status with brain metastases not suitable for surgical excision. Radiother Oncol, 88: 173-176 [DOI:10.1016/j.radonc.2008.05.020] [PMID]
16. Haie-Meder C, Pellae-Cosset B, Laplanche A, Lagrange J, Tuchais C, Nogues C, et al. (1993) Results of a randomized clinical trial comparing two radiation schedules in the palliative treatment of brain metastases. Radiother Oncol, 26: 111-116 [DOI:10.1016/0167-8140(93)90091-L] [PMID]
17. Murray K, Scott C, Greenberg H, Emami B, Seider M, Vora N, et al. (1997) A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: A report of the radiation therapy oncology group (RTOG) 9104. Int J Radiat Oncol Biol Phys, 39: 571-574. [DOI:10.1016/S0360-3016(97)00341-6] [PMID]
18. Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, et al. (2002) Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol, 20(17): 3644-3650. [DOI:10.1200/JCO.2002.04.140] [PMID]
19. DeAngelis L, Currie V, Kim J, Krol G, O'Hehir M, Farag F, et al. (1989) The combined use of radiation therapy and lonidamine in the treatment of brain metastases. J Neurooncol, 7(3): 241-7. [DOI:10.1007/BF00172917] [PMID]
20. Eyre H, Ohlsen J, Frank J, LoBuglio A, McCracken J, Weatherall T, et al. (1984) Randomized trial of radiotherapy versus radiotherapy plus metronidazole for the treatment metastatic cancer to brain. J Neurooncol, 2(4): 325-330. [DOI:10.1007/BF00178115] [PMID]
21. Komarnicky LT, Phillips T, Martz K, Asbell S, Isaacson S, Urtasun R (1991) A randomized phase iii protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with brain metastases (RTOG-7916). Int J Radiat Oncol Biol Phys, 20: 53-58. [DOI:10.1016/0360-3016(91)90137-S] [PMID]
22. Phillips T, Scott C, Leibel S, Rotman M, Weigensberg I (1995) Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: Report of RTOG trial 89-05. Int J Radiat Oncol Biol Phys, 33: 339-348. [DOI:10.1016/0360-3016(95)00168-X] [PMID]
23. Mehta M, Shapiro W, Phan S, et al. (2009) Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: Results of a phase III trial. Int J Radiat Oncol Biol Phys, 73: 1069-1076. [DOI:10.1016/j.ijrobp.2008.05.068] [PMID]
24. Scott C, Suh J, Stea B, Nabid A, Hackman J (2007) Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases. Am J Clin Oncol, 30: 580-587. [DOI:10.1097/COC.0b013e3180653c0d] [PMID]
25. Suh J, Stea B, Nabid A, et al. (2006) Phase III Study of Efaproxiral As an Adjunct to Whole-Brain Radiation Therapy for Brain Metastases. J Clin Oncol, 24: 106-114 [DOI:10.1200/JCO.2004.00.1768] [PMID]
26. O'Neill P, Bray P, Hawley S, Ward S, Park B (1998) 4-Aminoquinolines-Past, present, and future; A chemical perspective. Pharmacol Ther, 77: 29-58. [DOI:10.1016/S0163-7258(97)00084-3] [PMID]
27. Romanelli F, Smith K, Hoven A (2004) Chloroquine and Hydroxychloroquine as Inhibitors of Human Immunodeficiency Virus (HIV-1) Activity. Curr Pharm Des, 10: 2643-2648. [DOI:10.2174/1381612043383791] [PMID]
28. Katz S and Russell A (2011) Re-evaluation of antimalarials in treating rheumatic diseases: re-appreciation and insights into new mechanisms of action. Curr Opin Rheumatol, 23: 278-281. [DOI:10.1097/BOR.0b013e32834456bf] [PMID]
29. Eldredge H, DeNittis A, DuHadaway J, Chernick M, Metz R, Prendergast G (2013) Concurrent whole brain radiotherapy and short-course chloroquine in patients with brain metastases: a pilot trial. Radiat Oncol J, 2: 315-321. [DOI:10.1007/s13566-013-0111-x] [PMID] []
30. Rojas-Puentes L, Gonzalez-Pinedo M, Crismatt A, Ortega-Gomez A, Gamboa-Vignolle C, Nuñez-Gomez R, Dorantes-Gallareta Y, Arce-Salinas C, Arrieta O (2013) Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases. Radiat Oncol, 8: 209. [DOI:10.1186/1748-717X-8-209] [PMID] []
31. Brazil L, Swampillai A, Mak K, et al. (2018) P01.072 Hydroxychloroquine and short course radiotherapy for elderly patients with glioma: a randomised study. Neuro Oncol, 20: iii246-iii246. [DOI:10.1093/neuonc/noy139.114] []



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Volume 20, Issue 4 (10-2022) Back to browse issues page