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Predicting the efficacy of chemoradiotherapy for locally advanced human papilloma virus-related oropharyngeal squamous cell carcinoma using one course of TPF chemotherapy

  • Head and Neck
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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

The standard induction chemotherapy for head and neck cancer is TPF [cisplatin (CDDP), docetaxel (DOC), and 5-fluorouracil (5-FU)]. We assessed whether one course of TPF could predict the efficacy of chemoradiotherapy for human papilloma virus (HPV)-related oropharyngeal squamous cell carcinoma.

Methods

We retrospectively reviewed 51 patients with stage III–IV HPV-related oropharyngeal squamous cell carcinoma who received one course of TPF with CDDP 60 mg/m2, DOC 60 mg/m2, and 5-FU 600 mg/m2. We recommended chemoradiotherapy for patients with complete or partial response (CR/PR), and surgery for those with stable or progressive disease (SD/PD). The endpoints were TPF-related adverse events and efficacy, chemoradiotherapy efficacy, and 2-year survival.

Results

Neutropenia was the most common grade ≥ 3 adverse event (88%). No grade 5 adverse events occurred. TPF achieved CR in 4% of patients (2/51), PR in 73% (37/51), SD in 20% (10/51), and PD in 4% (2/51). Concurrent cetuximab and radiotherapy (bio-radiotherapy, BRT) were administered to 61% of patients (31/51), concurrent CDDP and radiotherapy (CDDP-RT) to 16% (8/51), RT alone to 2% (1/51), and surgery was performed for 22% (11/51). CR was achieved in 85% of the chemoradiotherapy group, and the rate tended to increase with TPF efficacy. CR was achieved in 84% (26/31) of patients receiving BRT, 88% (7/8) receiving CDDP-RT, and 100% (1/1) receiving RT. The 2-year survival rates were 92% overall, and 97% and 79% in the chemoradiotherapy and surgery groups, respectively.

Conclusions

When facing difficulty in deciding between chemoradiotherapy and surgery, one course of TPF may be an effective option.

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References

  1. Pignon JP, Bourhis J, Domenge C, Designé L (2000) Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 355:949–955

    Article  CAS  Google Scholar 

  2. 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 92:4–14

    Article  Google Scholar 

  3. Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Wengaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL, EORTC 24791/TAX 323 Study Group (2007) Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 357:1695–1704

    Article  CAS  Google Scholar 

  4. Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI, TAX 324 Study Group (2007) Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 357:1705–1715

    Article  CAS  Google Scholar 

  5. Ghi MG, Paccagnella A, Ferrari D, Foa P, Alterio D, Codecà C, Nolè F, Verri E, Orecchia R, Morelli F, Parisi S, Mastromauro C, Mione CA, Rossetto C, Polsinelli M, Koussis H, Loreggian L, Bonetti A, Campostrini F, Azzarello G, D’Ambrosio C, Bertoni F, Casanova C, Emiliani E, Guaraldi M, Bunkheila F, Bidoli P, Niespolo RM, Gava A, Massa E, Frattegiani A, Valduga F, Pieri G, Cipani T, Da Corte D, Chiappa F, Rulli E, GSTTC (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group (2007) Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial. Ann Oncol 28:2206–2212

    Article  Google Scholar 

  6. Haddad R, O’Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, Clark J, Sarlis N, Lorch J, Beitler J, Limaye S, Riley S, Posner M (2013) Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14:257–264

    Article  CAS  Google Scholar 

  7. Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, Brockstein BE, Agulnik MB, Mittal BB, Yunus F, Samant S, Raez LE, Mehra R, Kumar P, Ondrey F, Marchand P, Braegas B, Seiwert TY, Villaflor VM, Haraf DJ, Vokes EE (2014) Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol 32:2735–2743

    Article  CAS  Google Scholar 

  8. Hitt R, Grau JJ, Lopez-Pousa A, Berrocal A, García-Girón C, Irigoyen A, Sastre J, Martínez-Trufero J, Brandariz Castelo JA, Verger E, Cruz-Hernández JJ, Spanish Head and Neck Cancer Cooperative Group (TTCC) (2014) A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25:216–225

    Article  CAS  Google Scholar 

  9. Kiong KL, de Souza NN, Sultana R, Iyer NG (2018) Meta-analysis of induction chemotherapy as a selection marker for chemoradiation in the head and neck. Laryngoscope 128:1594–1601

    Article  Google Scholar 

  10. Urba S, Wolf G, Eisbruch A, Worden F, Lee J, Bradford C, Teknos T, Chepeha D, Prince M, Hogikyan N, Taylor J (2006) Single-cycle induction chemotherapy selects patients with advanced laryngeal cancer for combined chemoradiation: a new treatment paradigm. J Clin Oncol 24:593–598

    Article  CAS  Google Scholar 

  11. Vainshtein JM, Wu VF, Spector ME, Bradford CR, Wolf GT, Worden FP (2013) Chemoselection: a paradigm for optimization of organ preservation in locally advanced larynx cancer. Expert Rev Anticancer Ther 13:1053–1064

    Article  CAS  Google Scholar 

  12. Worden FP, Kumar B, Lee JS, Wolf GT, Cordell KG, Taylor JMG, Urba SG, Eisbruch A, Teknos TN, Chepeha DB, Prince ME, Tsien CI, D’Silva NJ, Yang K, Kurnit DM, Mason HL, Miller TH, Wallace NE, Bradford CR, Carey TE (2008) Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol 26:3138–3146

    Article  CAS  Google Scholar 

  13. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene F, Trotti A (eds) (2010) AJCC cancer staging manual, 7th edn. Springer, New York

    Google Scholar 

  14. Japan Society for Head and Neck Cancer (2018) General rules for clinical studies on head and neck cancer, 6th edn. Kanehara-shuppan, Tokyo

    Google Scholar 

  15. 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

    Article  CAS  Google Scholar 

  16. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Article  CAS  Google Scholar 

  17. Hirasawa K, Okamoto I, Motohashi R, Sato H, Takase S, Agata A, Takeda A, Tsukahara K (2017) The efficiency and adverse events of radiotherapy with cetuximab for Japanese head and neck cancer patients. Auris Nasus Larynx 44:724–728

    Article  Google Scholar 

  18. Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR (eds) (2017) AJCC cancer staging manual, 8th edn. Springer, New York

    Google Scholar 

  19. 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

    Article  CAS  Google Scholar 

  20. El-Naggar AK, Westra WH (2012) p16 expression as a surrogate marker for HPV-related oropharyngeal carcinoma: a guide for interpretative relevance and consistency. Head Neck 34:459–461

    Article  Google Scholar 

  21. Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, Galloway TJ, Phan J, Dignam JJ, Le QT (2019) Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet 393:40–50

    Article  CAS  Google Scholar 

  22. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, Dalby M, Mistry P, Sen M, O’Toole L, Al Booz H, Dyker K, Moleron R, Whitaker S, Brennan S, Cook A, Griffin M, Aynsley E, Rolles M, De Winton E, Chan A, Srinivasan D, Nixon I, Grumett J, Leemans CR, Buter J, Henderson J, Harrington K, McConkey C, Gray A, Dunn J, De-ESCALaTE HPV Trial Group (2019) Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 393:51–60

    Article  CAS  Google Scholar 

  23. Saito Y, Ando M, Omura G, Yasuhara K, Yoshida M, Takahashi W, Yamasoba T (2016) Induction chemotherapy for p16 positive oropharyngeal squamous cell carcinoma. Laryngoscope Investig Otolaryngol 1:28–32

    Article  Google Scholar 

  24. Misiukiewicz K, Gupta V, Miles BA, Bakst R, Genden E, Selkridge I, Surgeon JT, Rainey H, Camille N, Roy E, Zhang D, Ye F, Jia R, Moshier E, Bonomi M, Hwang M, Som P, Posner MR (2019) Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial. Oral Oncol 95:170–177

    Article  CAS  Google Scholar 

  25. Chidambaram S, Nakken ER, Kennedy W, Thorstad WL, Chen SY, Pipkorn P, Zevallos JP, Mazul AL (2020) Prognostic significance of smoking in human papillomavirus-positive oropharyngeal cancer under American joint committee on eighth edition cancer stage. Laryngoscope 130:1961–1966

    Article  Google Scholar 

  26. Nakano K, Sato Y, Toshiyasu T, Sato Y, Inagaki L, Tomomatsu J, Sasaki T, Shimbashi W, Fukushima H, Yonekawa H, Mitani H, Kawabata K, Takahashi S (2016) Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy. Mol Clin Oncol 4:303–309

    Article  CAS  Google Scholar 

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The authors have no financial relationships to disclose.

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji-shi, Tokyo, 193-0998, Japan

    Takahito Kondo, Atsuo Takeda, Naiue Kikawada, Yusuke Aihara & Yasuo Ogawa

  2. Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Kiyoaki Tsukahara, Isaku Okamoto, Hiroki Sato, Takuro Okada, Ryo Maruyama, Kosuke Hihara & Tatsuya Ito

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  1. Takahito Kondo
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Correspondence to Takahito Kondo.

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Ethical approval

The study was approved by the ethics committee of Tokyo Medical University (approval number T2020-0074). We conducted this study in compliance with the Declaration of Helsinki.

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Kondo, T., Tsukahara, K., Okamoto, I. et al. Predicting the efficacy of chemoradiotherapy for locally advanced human papilloma virus-related oropharyngeal squamous cell carcinoma using one course of TPF chemotherapy. Eur Arch Otorhinolaryngol 278, 3497–3506 (2021). https://doi.org/10.1007/s00405-020-06549-9

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  • DOI: https://doi.org/10.1007/s00405-020-06549-9

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