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Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma

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Abstract

Chemoradiotherapy (CRT) for locally-advanced head and neck squamous cell carcinoma (LA-HSNCC) yields 5-year survival rates near 50% despite causing significant toxicity. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase metabolic inhibitor, reduces tumor lactate production and has been used in cancer therapy previously. The safety of adding this agent to CRT is unknown. Our randomized, placebo-controlled, double-blind phase II study added DCA to cisplatin-based CRT in patients with LA-HNSCC. The primary endpoint was safety by adverse events (AEs). Secondary endpoints compared efficacy via 3-month end-of-treatment response, 5-year progression-free and overall survival. Translational research evaluated pharmacodynamics of serum metabolite response. 45 participants (21 DCA, 24 Placebo) were enrolled from May 2011-April 2014. Higher rates of all-grade drug related fevers (43% vs 8%, p = 0.01) and decreased platelet count (67% vs 33%, p = 0.02) were seen in DCA versus placebo. However, there were no significant differences in grade 3/4 AE rates. Treatment compliance to DCA/placebo, radiation therapy, and cisplatin showed no significant difference between groups. While end-of-treatment complete response rates were significantly higher in the DCA group compared to placebo (71.4% vs 37.5%, p = 0.0362), survival outcomes were not significantly different between groups. Treatment to baseline metabolites demonstrated a significant drop in pyruvate (0.47, p < 0.005) and lactate (0.61, p < 0.005) in the DCA group. Adding DCA to cisplatin-based CRT appears safe with no detrimental effect on survival and expected metabolite changes compared to placebo. This supports further investigation into combining metabolic agents to CRT. Trial registration number: NCT01386632, Date of Registration: July 1, 2011.

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Availability of data and materials

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to patient privacy.

References

  1. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee D-J, Leaf A, Ensley J, Cooper J (2003) Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer. N Engl J Med 349:2091–2098. https://doi.org/10.1056/NEJMoa031317

    Article  CAS  PubMed  Google Scholar 

  2. Adelstein DJ, Li Y, Adams GL, Wagner H, Kish JA, Ensley JF, Schuller DE, Forastiere AA (2003) An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer. J Clin Oncol 21:92–98. https://doi.org/10.1200/JCO.2003.01.008

    Article  PubMed  Google Scholar 

  3. Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS (2013) Long-Term Results of RTOG 91–11: A Comparison of Three Nonsurgical Treatment Strategies to Preserve the Larynx in Patients With Locally Advanced Larynx Cancer. J Clin Oncol 31:845

    Article  CAS  Google Scholar 

  4. Pignon JP, Le Maitre A, Maillard E, Bourhis J, Mach-Nc Collaborative Group (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 92(1):4–14. https://doi.org/10.1016/j.radonc.2009.04.014

    Article  PubMed  Google Scholar 

  5. Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, Axelrod RS (2014) Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522. J Clin Oncol 32:2940–2950. https://doi.org/10.1200/JCO.2013.53.5633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Miyauchi S, Kim SS, Pang J, Gold KA, Gutkind JS, Califano JA, Mell LK, Cohen EEW, Sharabi AB (2019) Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics. Clin Cancer Res Off J Am Assoc Cancer Res 25:4211–4223. https://doi.org/10.1158/1078-0432.CCR-18-0871

    Article  CAS  Google Scholar 

  7. Yeung SJ, Pan J, Lee M-H (2008) Roles of p53, Myc and HIF-1 in Regulating Glycolysis – the Seventh Hallmark of Cancer. Cell Mol Life Sci 65:3981–3999. https://doi.org/10.1007/s00018-008-8224-x

    Article  CAS  PubMed  Google Scholar 

  8. Brun E, Kjellén E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, Perfekt R, Wennerberg J, Strand SE (2002) FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck 24:127–135. https://doi.org/10.1002/hed.10037

    Article  PubMed  Google Scholar 

  9. Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller-Klieser W (2001) Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol 51:349–353. https://doi.org/10.1016/S0360-3016(01)01630-3

    Article  CAS  Google Scholar 

  10. Walenta S, Schroeder T, Mueller-Klieser W (2004) Lactate in Solid Malignant Tumors: Potential Basis of a Metabolic Classification in Clinical Oncology. Curr Med Chem 11:2195–2204. https://doi.org/10.2174/0929867043364711

    Article  CAS  PubMed  Google Scholar 

  11. Gottfried E, Kunz-Schughart LA, Ebner S, Mueller-Klieser W, Hoves S, Andreesen R, Mackensen A, Kreutz M (2006) Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood 107:2013–2021. https://doi.org/10.1182/blood-2005-05-1795

    Article  CAS  PubMed  Google Scholar 

  12. Puig-Kröger A, Muñiz-Pello O, Selgas R, Criado G, Bajo M-A, Sánchez-Tomero JA, Alvarez V, del Peso G, Sánchez-Mateos P, Holmes C, Faict D, López-Cabrera M, Madrenas J, Corbí AL (2003) Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucose-degradation products. J Leukoc Biol 73:482–492. https://doi.org/10.1189/jlb.0902451

    Article  CAS  PubMed  Google Scholar 

  13. Shime H, Yabu M, Akazawa T, Kodama K, Matsumoto M, Seya T, Inoue N (2008) Tumor-Secreted Lactic Acid Promotes IL-23/IL-17 Proinflammatory Pathway. J Immunol 180:7175–7183. https://doi.org/10.4049/jimmunol.180.11.7175

    Article  CAS  PubMed  Google Scholar 

  14. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, Renner K, Timischl B, Mackensen A, Kunz-Schughart L, Andreesen R, Krause SW, Kreutz M (2007) Inhibitory effect of tumor cell–derived lactic acid on human T cells. Blood 109:3812–3819. https://doi.org/10.1182/blood-2006-07-035972

    Article  CAS  PubMed  Google Scholar 

  15. Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn M-J, Soria A, Machiels J-P, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ, Acosta-Rivera M, Adkins DR, Aghmesheh M, Ahn M-J, Airoldi M, Aleknavicius E, Al-Farhat Y, Algazi AP, Almokadem S, Alyasova A, Bauman JR, Benasso M, Berrocal A, Bray V, Burtness BA, Caponigro F, Castro A, Cescon TP, Chan K, Chaudhry A, Chauffert B, Cohen E, Csoszi T, De Boer JP, Delord J-P, Dietz A, Dinis J, Dupuis C, Digue L, Erfan J, Escobar Alvarez Y, Evans M, Fidler MJ, Forster MD, Friesland S, Ganti AK, Geoffrois L, Grant C, Gruenwald V, Harrington K, Hoffmann T, Horvai G, Inciura A, Jang R, Jankowska P, Jimeno A, Joseph M, Juarez Ramiro A, Karaszewska B, Kawecki A, Keilholz U, Keller U, Kim S-B, Kocsis J, Kotecki N, Kozloff MF, Lambea J, Landherr L, Lantsukhay Y, Lazarev SA, Lee LW, Le Tourneau C, Licitra L, Lifirenko ID, Mach N, Martincic D, Matorin OV, McGrath M, Machiels J-P, Mehra R, Misiukiewicz K, Morris JC, Mufazalov FF, Niu J, Pamoorthy Srinivasan D, Perez Segura P, Rauch D, Ribeiro ML, Rodriguez C, Rolland F, Russo A, Ruzsa A, Sanches F, Shin S-W, Shtiveland M, Soulieres D, Soria A, Specenier P, Szekanecz E, Szota J, van Herpen CML, Velez-Cortes HA, Walsh WV, Wilop S, Winterhalder R, Wojtukiewicz M, Wong D, Zandberg D (2019) Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 393:156–167. https://doi.org/10.1016/S0140-6736(18)31999-8

    Article  CAS  PubMed  Google Scholar 

  16. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Docampo LCI, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2017) Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 375:1856–1867

    Article  Google Scholar 

  17. Machiels J-PH, Licitra L, Rischin D, Waldron J, Burtness B, Gregoire V, Shekar T, Brown HM, Cheng JD, Siu LL (2017) KEYNOTE-412: Pembrolizumab (pembro) in combination with chemoradiation versus chemoradiation alone in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). J Clin Oncol 35:TPS6090. https://doi.org/10.1200/JCO.2017.35.15_suppl.TPS6090

    Article  Google Scholar 

  18. Cohen EE, Ferris RL, Psyrri A, Haddad R, Tahara M, Bourhis J, Harrington KJ, Chang PM-H, Lin J-C, Razaq M, Teixeira MM, Lovey J, Chamois J, Rueda Dominguez A, Hu C, Dvorkin M, De Beukelaer S, Pavlov D, Thurm H, Lee N (2020) 910O Primary results of the phase III JAVELIN head & neck 100 trial: Avelumab plus chemoradiotherapy (CRT) followed by avelumab maintenance vs CRT in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Ann Oncol 31:S658. https://doi.org/10.1016/j.annonc.2020.08.1025

    Article  Google Scholar 

  19. Stacpoole PW, Kurtz TL, Han Z, Langaee T (2008) Role of dichloroacetate in the treatment of genetic mitochondrial diseases☆. Adv Drug Deliv Rev 60:1478–1487. https://doi.org/10.1016/j.addr.2008.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Michelakis ED, Webster L, Mackey JR (2008) Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br J Cancer 99:989–994. https://doi.org/10.1038/sj.bjc.6604554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wigfield SM, Winter SC, Giatromanolaki A, Taylor J, Koukourakis ML, Harris AL (2008) PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer. Br J Cancer 98:1975–1984. https://doi.org/10.1038/sj.bjc.6604356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. McFate T, Mohyeldin A, Lu H, Thakar J, Henriques J, Halim ND, Wu H, Schell MJ, Tsang TM, Teahan O, Zhou S, Califano JA, Jeoung NH, Harris RA, Verma A (2008) Pyruvate Dehydrogenase Complex Activity Controls Metabolic and Malignant Phenotype in Cancer Cells. J Biol Chem 283:22700–22708. https://doi.org/10.1074/jbc.M801765200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dunbar EM, Coats BS, Shroads AL, Langaee T, Lew A, Forder JR, Shuster JJ, Wagner DA, Stacpoole PW (2014) Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors. Invest New Drugs 32:452–464. https://doi.org/10.1007/s10637-013-0047-4

    Article  CAS  PubMed  Google Scholar 

  24. Chu QS-C, Sangha R, Spratlin J, Vos LJ, Mackey JR, McEwan AJB, Venner P, Michelakis ED (2015) A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors. Invest New Drugs 33:603–610. https://doi.org/10.1007/s10637-015-0221-y

    Article  CAS  PubMed  Google Scholar 

  25. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM. Ann Surg Oncol 17:1471–1474. https://doi.org/10.1245/s10434-010-0985-4

    Article  PubMed  Google Scholar 

  26. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  27. Huang J, Mondul AM, Weinstein SJ, Derkach A, Moore SC, Sampson JN, Albanes D (2019) Prospective serum metabolomic profiling of lethal prostate cancer. Int J Cancer 145:3231–3243. https://doi.org/10.1002/ijc.32218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Stacpoole PW, Gilbert LR, Neiberger RE, Carney PR, Valenstein E, Theriaque DW, Shuster JJ (2008) Evaluation of Long-term Treatment of Children With Congenital Lactic Acidosis With Dichloroacetate. Pediatrics 121:e1223–e1228. https://doi.org/10.1542/peds.2007-2062

    Article  PubMed  Google Scholar 

  29. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. N Engl J Med 363:24–35. https://doi.org/10.1056/NEJMoa0912217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Osazuwa-Peters N, Adjei Boakye E, Chen BY, Tobo BB, Varvares MA (2018) Association Between Head and Neck Squamous Cell Carcinoma Survival, Smoking at Diagnosis, and Marital Status. JAMA Otolaryngol Neck Surg 144:43–50. https://doi.org/10.1001/jamaoto.2017.1880

    Article  Google Scholar 

  31. Zaboli D, Tan M, Gogineni H, Lake S, Fan K, Zahurak ML, Messing B, Ulmer K, Zinreich ES, Levine MA, Tang M, Pai SI, Blanco RG, Saunders JR, Best SR, Califano JA, Ha PK (2012) Hyperfractionated Radiotherapy with Concurrent Cisplatin/5-Fluorouracil for Locoregional Advanced Head and Neck Cancer: Analysis of 105 Consecutive Patients. Int J Otolaryngol 2012:e754191. https://doi.org/10.1155/2012/754191

    Article  Google Scholar 

  32. Roberts JC, Li G, Reitzel LR, Wei Q, Sturgis EM (2010) No Evidence of Sex-Related Survival Disparities among Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care: A Matched-Pair Analysis. Clin Cancer Res 16:5019–5027. https://doi.org/10.1158/1078-0432.CCR-10-0755

    Article  PubMed  PubMed Central  Google Scholar 

  33. Mazul AL, Naik AN, Zhan KY, Stepan KO, Old MO, Kang SY, Nakken ER, Puram SV (2021) Gender and race interact to influence survival disparities in head and neck cancer. Oral Oncol 112:105093. https://doi.org/10.1016/j.oraloncology.2020.105093

    Article  PubMed  Google Scholar 

  34. Fakhry C, Westra WH, Wang SJ, van Zante A, Zhang Y, Rettig E, Yin LX, Ryan WR, Ha PK, Wentz A, Koch W, Richmon JD, Eisele DW, D’Souza G (2017) The Prognostic Role of Sex, Race, and Human Papillomavirus in Oropharyngeal and Nonoropharyngeal Head and Neck Squamous Cell Cancer. Cancer 123:1566–1575. https://doi.org/10.1002/cncr.30353

    Article  CAS  PubMed  Google Scholar 

  35. Marcus C, Ciarallo A, Tahari AK, Mena E, Koch W, Wahl RL, Kiess AP, Kang H, Subramaniam RM (2014) Head and Neck PET/CT: Therapy Response Interpretation Criteria (Hopkins Criteria)–Interreader Reliability, Accuracy, and Survival Outcomes. J Nucl Med 55:1411–1416. https://doi.org/10.2967/jnumed.113.136796

    Article  CAS  PubMed  Google Scholar 

  36. Mehanna H, Wong W-L, McConkey CC, Rahman JK, Robinson M, Hartley AGJ, Nutting C, Powell N, Al-Booz H, Robinson M, Junor E, Rizwanullah M, von Zeidler SV, Wieshmann H, Hulme C, Smith AF, Hall P, Dunn J (2016) PET-NECK Trial Management Group: PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med 374:1444–1454. https://doi.org/10.1056/NEJMoa1514493

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the patients and families who participated in this research. Additionally, they would like to acknowledge the Sanford Research Clinical Research Coordinators, Histology and Imaging Core, and Research Design and Biostatistics Core.

Funding

Translational metabolite analysis was supported by Center of Biology Research Excellence Award No. 5P20-GM103548-09, sponsored by the National Institute of General Medical Science. Funding for the clinical trial was provided by Sanford Research.

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Authors and Affiliations

  1. Sanford Cancer Center, 1309 W. 17th Street, Suite 101, Sioux Falls, SD, 57104, USA

    Steven F. Powell, Miroslaw Mazurczak, Jonathon S. Bleeker, Michele M. Lohr, Steven C. McGraw & William C. Spanos

  2. Sanford Roger Maris Cancer Center, 820 4th St N, Fargo, ND, 58102, USA

    Louis H. Geeraerts, Matthew Tinguely & Ashley W. Jensen

  3. Sanford Research, 301 East 60th St N, Sioux Falls, SD, 57104, USA

    Steven F. Powell, Miroslaw Mazurczak, Jonathon S. Bleeker, Christie A. Ellison, Lora J. Black, Valerie J. Reed, W. Keith Miskimins & William C. Spanos

  4. University of South Dakota Sanford School of Medicine, 414 E. Clark St., Vermillion, SD, 57069, USA

    Steven F. Powell, Miroslaw Mazurczak, Jonathon S. Bleeker, Michele M. Lohr, Steven C. McGraw, Lora J. Black, John H. Lee & William C. Spanos

  5. St. Joseph Mercy Cancer Center, 5301 Elliott Dr. Ste 210, Ypsilanti, MI, 48197, USA

    Elie G. Dib

  6. University of South Dakota School of Health Sciences, 414 E. Clark St., Vermillion, SD, 57069, USA

    Susan E. Puumala

  7. Avera Cancer Institute, 1000 E 23rd St, Sioux Falls, SD, 57105, USA

    John H. Lee

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Contributions

S.C.M., M.M.L., S.E.P., W.K.M, J.H.L., W.C.S. contributed to conception and design; Material preparation, data collection and analysis were performed by S.F.P., M.M., E.G.D., J.S.B., L.H.G., M.T., M.M.L., S.C.M., A.W.J., C.A.E., V.J.R. J.H.L., W.C.S.; The first draft of the manuscript was written by S.F.P., C.A.E., V.J.R, S.E.P., J.H.L., W.C.S and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Steven F. Powell.

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Ethics approval and consent to participate

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Sanford Research (protocol code 03–11-028 and date of approval March 24th, 2011). Informed consent was obtained from all subjects involved in the study.

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Applicable, obtained through informed consent.

Informed consent

Written informed consent was obtained from all subjects involved in the study.

Research involving Human Participants and/or Animals

The study involved human participants and was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Sanford Research (protocol code 03–11-028 and date of approval March 24th, 2011).

Competing Interests

Steven Powell has received research grant support to the institution from Merck, Bristol Myers Squib, Pfizer, Vyriad, Incyte, Actuate, Genentech, Seattle Genetics anded consulting support to the institution from Bristol Myers Squibb. William Spanos received consulting support for Bristol Myers Squibb, Regeneron, and Merck. The other authors declare no competing interests.

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Powell, S.F., Mazurczak, M., Dib, E.G. et al. Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma. Invest New Drugs 40, 622–633 (2022). https://doi.org/10.1007/s10637-022-01235-5

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