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01-01-2020 | Minocycline | Original Article

Minocycline for symptom reduction during radiation therapy for head and neck cancer: a randomized clinical trial

Authors: G. Brandon Gunn, Tito R. Mendoza, Adam S. Garden, Xin Shelley Wang, Qiuling Shi, William H. Morrison, Steven J. Frank, Jack Phan, Clifton D. Fuller, Mark S. Chambers, Ehab Y. Hanna, Charles Lu, David I. Rosenthal, Charles S. Cleeland

Published in: Supportive Care in Cancer | Issue 1/2020

Abstract

Purpose

Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC).

Methods

Eligible patients for this blinded, placebo–controlled trial were adults with T0–3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN).

Results

We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD = 1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery.

Conclusions

Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design.

Garden AS, Kies MS, Morrison WH, Weber RS, Frank SJ, Glisson BS, Gunn GB, Beadle BM, Ang KK, Rosenthal DI, Sturgis EM (2013) Outcomes and patterns of care of patients with locally advanced oropharyngeal carcinoma treated in the early 21st century. Radiat Oncol 8(21). https://doi.org/10.1186/1748-717X-8-21

Rosenthal DI, Mendoza TR, Fuller CD, Hutcheson KA, Wang XS, Hanna EY, Lu C, Garden AS, Morrison WH, Cleeland CS, Gunn GB (2014) Patterns of symptom burden during radiotherapy or concurrent chemoradiotherapy for head and neck cancer: a prospective analysis using the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module. Cancer 120(13):1975–1984. https://doi.org/10.1002/cncr.28672 CrossRefPubMed

Goepfert RP, Fuller CD, Gunn GB, Hanna EY, Lewin JS, Zaveri JS, Hubbard RM, Barrow MP, Hutcheson KA (2017) Symptom burden as a driver of decisional regret in long-term oropharyngeal carcinoma survivors. Head Neck 39(11):2151–2158. https://doi.org/10.1002/hed.24879 CrossRefPubMed

Mirghani H, Blanchard P (2018) Treatment de-escalation for HPV-driven oropharyngeal cancer: where do we stand? Clin Transl Radiat Oncol 8:4–11. https://doi.org/10.1016/j.ctro.2017.10.005 CrossRefPubMed

Dantzer R, Kelley KW (2007) Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21(2):153–160. https://doi.org/10.1016/j.bbi.2006.09.006 CrossRefPubMed

Dantzer R, Meagher MW, Cleeland CS (2012) Translational approaches to treatment-induced symptoms in cancer patients. Nat Rev Clin Oncol 9(7):414–426. https://doi.org/10.1038/nrclinonc.2012.88 CrossRefPubMedPubMedCentral

Garrido-Mesa N, Zarzuelo A, Galvez J (2013) Minocycline: far beyond an antibiotic. Br J Pharmacol 169(2):337–352. https://doi.org/10.1111/bph.12139 CrossRefPubMedPubMedCentral

Smith CJ, Sayles H, Mikuls TR, Michaud K (2011) Minocycline and doxycycline therapy in community patients with rheumatoid arthritis: prescribing patterns, patient-level determinants of use, and patient-reported side effects. Arthritis Res Ther 13(5):R168. https://doi.org/10.1186/ar3491 CrossRefPubMedPubMedCentral

O’Dell JR, Blakely KW, Mallek JA, Eckhoff PJ, Leff RD, Wees SJ, Sems KM, Fernandez AM, Palmer WR, Klassen LW, Paulsen GA, Haire CE, Moore GF (2001) Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum 44(10):2235–2241CrossRefPubMed

10.

Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J (2001) Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 21(8):2580–2588CrossRefPubMedPubMedCentral

11.

Plane JM, Shen Y, Pleasure DE, Deng W (2010) Prospects for minocycline neuroprotection. Arch Neurol 67(12):1442–1448. https://doi.org/10.1001/archneurol.2010.191 CrossRefPubMedPubMedCentral

12.

Li C, Yuan K, Schluesener H (2013) Impact of minocycline on neurodegenerative diseases in rodents: a meta-analysis. Rev Neurosci 24(5):553–562. https://doi.org/10.1515/revneuro-2013-0040 CrossRefPubMed

13.

Bonelli RM, Hodl AK, Hofmann P, Kapfhammer HP (2004) Neuroprotection in Huntington’s disease: a 2-year study on minocycline. Int Clin Psychopharmacol 19(6):337–342CrossRefPubMed

14.

Leporini C, Saullo F, Filippelli G, Sorrentino A, Lucia M, Perri G, Gattuta GL, Infusino S, Toscano R, Dima G, Olivito V, Paletta L, Bottoni U, De Sarro G (2013) Management of dermatologic toxicities associated with monoclonal antibody epidermal growth factor receptor inhibitors: a case review. J Pharmacol Pharmacother 4(Suppl 1):S78–S85. https://doi.org/10.4103/0976-500X.120966 CrossRefPubMedPubMedCentral

15.

Melosky B, Anderson H, Burkes RL, Chu Q, Hao D, Ho V, Ho C, Lam W, Lee CW, Leighl NB, Murray N, Sun S, Winston R, Laskin JJ (2016) Pan Canadian Rash Trial: a randomized phase III trial evaluating the impact of a prophylactic skin treatment regimen on epidermal growth factor receptor-tyrosine kinase inhibitor-induced skin toxicities in patients with metastatic lung cancer. J Clin Oncol 34(8):810–815. https://doi.org/10.1200/JCO.2015.62.3918 CrossRefPubMed

16.

Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ (2012) Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 135(Pt 4):1224–1236. https://doi.org/10.1093/brain/aws072 CrossRefPubMed

17.

Rosenthal DI, Mendoza TR, Chambers MS, Asper JA, Gning I, Kies MS, Weber RS, Lewin JS, Garden AS, Ang KK, X SW, Cleeland CS (2007) Measuring head and neck cancer symptom burden: the development and validation of the M. D. Anderson symptom inventory, head and neck module. Head Neck 29(10):923–931. https://doi.org/10.1002/hed.20602 CrossRefPubMed

18.

Shi Q, Wang XS, Li G, Shah ND, Orlowski RZ, Williams LA, Mendoza TR, Cleeland CS (2015) Racial/ethnic disparities in inflammatory gene single-nucleotide polymorphisms as predictors of a high risk for symptom burden in patients with multiple myeloma 1 year after diagnosis. Cancer 121(7):1138–1146. https://doi.org/10.1002/cncr.29154 CrossRefPubMed

19.

Wang XS, Shi Q, Shah ND, Heijnen CJ, Cohen EN, Reuben JM, Orlowski RZ, Qazilbash MH, Johnson VE, Williams LA, Mendoza TR, Cleeland CS (2014) Inflammatory markers and development of symptom burden in patients with multiple myeloma during autologous stem cell transplantation. Clin Cancer Res 20(5):1366–1374. https://doi.org/10.1158/1078-0432.CCR-13-2442 CrossRefPubMedPubMedCentral

20.

Wang XS, Shi Q, Williams LA, Mao L, Cleeland CS, Komaki RR, Mobley GM, Liao Z (2010) Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy. Brain Behav Immun 24(6):968–974. https://doi.org/10.1016/j.bbi.2010.03.009 CrossRefPubMedPubMedCentral

21.

Wang XS, Williams LA, Krishnan S, Liao Z, Liu P, Mao L, Shi Q, Mobley GM, Woodruff JF, Cleeland CS (2012) Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. Brain Behav Immun 26(5):699–705. https://doi.org/10.1016/j.bbi.2011.12.007 CrossRefPubMedPubMedCentral

22.

Wood LJ, Weymann K (2013) Inflammation and neural signaling: etiologic mechanisms of the cancer treatment-related symptom cluster. Curr Opin Support Palliat Care 7(1):54–59. https://doi.org/10.1097/SPC.0b013e32835dabe3 CrossRefPubMedPubMedCentral

23.

Kwekkeboom KL, Tostrud L, Costanzo E, Coe CL, Serlin RC, Ward SE, Zhang Y (2018) The role of inflammation in the pain, fatigue, and sleep disturbance symptom cluster in advanced cancer. J Pain Symptom Manag 55(5):1286–1295. https://doi.org/10.1016/j.jpainsymman.2018.01.008 CrossRef

Title: Minocycline for symptom reduction during radiation therapy for head and neck cancer: a randomized clinical trial
Authors: G. Brandon Gunn
Tito R. Mendoza
Adam S. Garden
Xin Shelley Wang
Qiuling Shi
William H. Morrison
Steven J. Frank
Jack Phan
Clifton D. Fuller
Mark S. Chambers
Ehab Y. Hanna
Charles Lu
David I. Rosenthal
Charles S. Cleeland
Publication date: 01-01-2020
Publisher: Springer Berlin Heidelberg
Keywords: Minocycline
Radiotherapy
Fatigue
Published in: Supportive Care in Cancer / Issue 1/2020
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-019-04791-4

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