Strahlentherapie und Onkologie

, Volume 190, Issue 9, pp 823–831 | Cite as

Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas

  • Antonin Levy
  • Pierre Blanchard
  • Sara Bellefqih
  • Nacéra Brahimi
  • Joël Guigay
  • François Janot
  • Stéphane Temam
  • Jean Bourhis
  • Eric Deutsch
  • Nicolas Daly-Schveitzer
  • Yungan Tao
Original article

Abstract

Aim

The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC).

Patients and methods

Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m2, every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005).

Results

Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2–3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1–3 did not. BRT patients had more G3–4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3–4 gastrointestinal toxicities (p < 0.001).

Conclusion

This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.

Keywords

Head-and-neck cancer Chemoradiotherapy Antibodies, monoclonal, humanized Epidermal growth factor receptor inhibitors Toxicity 

Strahlentherapie in Kombination mit platinbasierter Chemotherapie oder Cetuximab zur Behandlung von lokal fortgeschrittenen Plattenepithelkarzinomen im Kopf-Hals-Bereich

Zusammenfassung

Ziel

Die Therapieeffektivität mit Platin-basierter Radiochemotherapie (CRT) und Cetuximab-basierter Radiobiotherapie (BRT) in der Behandlung von lokal fortgeschrittenen Kopf-Hals-Plattenepithelkarzinomen („head-and-neck squamous cell carcinoma“, HNSCC) wurden verglichen.

Patienten und Methoden

Zwischen 2006 und 2012 wurden in unserem Institut 265 Patienten mit lokal fortgeschrittenem HNSCC behandelt. In der CRT-Gruppe waren 3 Cisplatin-Zyklen (n = 194, 73 %; 100 mg/m2 alle 3 Wochen) und in der BRT-Gruppe (n = 71, 27 %) wöchentlich Cetuximab angesagt. Patienten mit BRT-Behandlung hatten eine erhöhte Anzahl von relevanten Begleiterkrankungen (Charlson-Index > 2) im Vergleich zur CRT-Gruppe (p = 0,005).

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 29 Monate für die Gesamtgruppe. In der CRT-Gruppe erhielten 56 % der Patienten die geplanten 3 Zyklen (92 % mindestens 2 Zyklen) und 79 % der Patienten mit BRT erhielten wenigstens 6 Zyklen. Die 2-Jahres-Gesamtüberlebensrate und die rezidivfreie Überlebensrate (PFS) lagen bei 72 respektive 61 %. In der multivariaten Analyse (MVA) waren T4-Stadium, N2–3-befallene Lymphknoten, Raucherstatus (Raucher verglichen mit Nichtrauchern) und nicht-oropharyngeale Bereiche in der Gesamtüberlebensrate nicht signifikant, während die BRT grenzwertig signifikant war (p = 0,054). Die lokoregionale 2-Jahres-Kontrolle (LRC) und die fernmetastasenfreien (DC-)Raten betrugen 73 % und 79 %. Die CRT wies eine verbesserte LRC (76 % für CRT vs. 61 % für BRT 2 Jahre LRC) und DC (2-Jahres-Überlebensrate: 81 % für CRT vs. 68 % bei BRT) im Vergleich zur BRT auf (p < 0,001 und p = 0,01 im MVA). Subgruppenanalysen zeigten, dass die LRC für Patienten mit einer T4-Erkrankung mit CRT (vs. BRT) deutlich besser ausfiel als für T1–3-Stadien. BRT-Patienten wiesen höhere Komplikationsraten Grad 3–4 (p < 0,001), CRT-Patienten eine höhere Rate an Sondenernährung (p = 0,006) und Magen-Darm-Nebenwirkungen Grad 3–4 auf (p < 0,001).

Fazit

Diese retrospektive Analyse zeigt eine verbesserte LRC in lokal fortgeschrittenen HNSCC mit Cisplatin-basierter CRT bezüglich zu Cetuximab-basierten BRT und einen nicht-signifikanten Trend für OS.

Schlüsselwörter

Kopf-Hals-Tumoren Radiochemotherapie Antikörper, monoklonal Wachstumsfaktorrezeptorhemmer, epidermaler Nebenwirkungen 

References

  1. 1.
    Pignon JP, Bourhis J, Domenge C et al (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 355:949–955CrossRefPubMedGoogle Scholar
  2. 2.
    Pignon JP, le Maître A, Maillard E et al (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92:4CrossRefPubMedGoogle Scholar
  3. 3.
    Machtay M, Moughan J, Trotti A et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26:3582–3589CrossRefPubMedGoogle Scholar
  4. 4.
    Forastiere AA, Zhang Q, Weber RS et al (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 31:845–852PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Adelstein DJ, Saxton JP, Rybicki LA et al (2006) Multiagent concurrent chemoradiotherapy for locoregionally advanced squamous cell head and neck cancer: mature results from a single institution. J Clin Oncol 24:1064–1071CrossRefPubMedGoogle Scholar
  6. 6.
    Bonner JA, Harari PM, Giralt J et al (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11:21–28CrossRefPubMedGoogle Scholar
  7. 7.
    Lefebvre JL, Pointreau Y, Rolland F et al (2013) Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN Randomized Phase II Study. J Clin Oncol 31:853–859CrossRefPubMedGoogle Scholar
  8. 8.
    Koutcher L, Sherman E, Fury M et al (2011) Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 811:915–922CrossRefGoogle Scholar
  9. 9.
    Caudell JJ, Sawrie SM, Spencer SA et al (2008) Locoregionally advanced head and neck cancer treated with primary radiotherapy: a comparison of the addition of cetuximab or chemotherapy and the impact of protocol treatment. Int J Radiat Oncol Biol Phys 71:676–681CrossRefPubMedGoogle Scholar
  10. 10.
    Walsh L, Gillham C, Dunne M et al (2011) Toxicity of cetuximab versus cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer (LAHNSCC). Radiother Oncol 98:38CrossRefPubMedGoogle Scholar
  11. 11.
    Budach W, Bölke E, Homey B (2007) Severe cutaneous reaction during radiation therapy with concurrent cetuximab. N Engl J Med 357:514–515CrossRefPubMedGoogle Scholar
  12. 12.
    Forastiere AA, Goepfert H, Maor M et al (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349:2091–2098CrossRefPubMedGoogle Scholar
  13. 13.
    Tao Y, Daly-Schveitzer N, Lusinchi A et al (2010) Advances in radiotherapy of head and neck cancers. Curr Opin Oncol 22:194–199CrossRefPubMedGoogle Scholar
  14. 14.
    Ghi MG, Paccagnella A, Ferrari D et al (2013) A phase II–III study comparing concomitant chemoradiotherapy (CRT) versus cetuximab/RT (CET/RT) with or without induction docetaxel/cisplatin/5-fluorouracil (TPF) in locally advanced head and neck squamous cell carcinoma (LASCCHN): Efficacy results (NCT01086826). J Clin Oncol 31:(Suppl; Abstr 6003)Google Scholar
  15. 15.
    Ley J, Mehan P, Wildes TM, et al (2012) Concurrent cisplatin vs. cetuximab with definitive radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC): a retrospective comparison. Multidisciplinary Head and Neck Cancer Symposium, Phoenix, AZ, 26–28 January, (Abstr 163)Google Scholar
  16. 16.
    Bourhis J, Sire C, Graff P et al (2012) Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99–02): an open-label phase 3 randomised trial. Lancet Oncol 13:145–153CrossRefPubMedGoogle Scholar
  17. 17.
    Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Blanchard P, Baujat B, Holostenco V et al; MACH-CH Collaborative Group (2011) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol 100:33–40CrossRefPubMedGoogle Scholar
  19. 19.
    O’Sullivan B, Huang SH, Siu LL et al (2013) Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol 31:543–550CrossRefPubMedGoogle Scholar
  20. 20.
    Denis F, Garaud P, Bardet E et al (2004) Final results of the 94–01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22:69–76CrossRefPubMedGoogle Scholar
  21. 21.
    Bernier J, Domenge C, Ozsahin M et al (2004) European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350:1945–1952CrossRefPubMedGoogle Scholar
  22. 22.
    Deantonio L, Masini L, Brambilla M et al (2013) Dysphagia after definitive radiotherapy for head and neck cancer. Correlation of dose–volume parameters of the pharyngeal constrictor muscles. Strahlenther Onkol 189:230–236CrossRefPubMedGoogle Scholar
  23. 23.
    Bölke E, Gerber PA, Lammering G et al (2008) Development and management of severe cutaneous side effects in head-and-neck cancer patients during concurrent radiotherapy and cetuximab. Strahlenther Onkol 184:105–110CrossRefPubMedGoogle Scholar
  24. 24.
    Selzer E, Liederer S, Lemaire C et al (2011) Incidence of dermatitis in head and neck cancer patients treated with primary radiotherapy and cetuximab. Strahlenther Onkol 187:373–377CrossRefPubMedGoogle Scholar
  25. 25.
    Deutsch E, Lemanski C, Pignon JP et al (2013) Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial. Ann Oncol 24:2834–2838CrossRefPubMedGoogle Scholar
  26. 26.
    Riaz N, Baschnagel A, Adkins D et al (2013) Multi-institution analysis of concurrent chemoradiation therapy with cisplatin (CDDP) versus cetuximab (C225) in locally-advanced squamous cell carcinoma of the head and neck (LA-HNSCC): can HPV help decide which agent? Int J Radiat Oncol Biol Phys 87:(Suppl 78–79; Abstr 191)Google Scholar
  27. 27.
    Psyrri A, Licitra L, De Blas B et al (2012) Safety and efficacy of cisplatin plus 5-FU and cetuximab in HPV-positive and HPV-negative recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): analysis of the phase iii extreme trial. ESMO Annual Congress, Abstr 1018OGoogle Scholar
  28. 28.
    Deberne M, Levy A, Mondini M et al (2013) The combination of antiviral agent cidofovir and anti-EGFR antibody cetuximab exerts an antiproliferative effect on HPV positive cervical cancer cell lines in vitro and in vivo xenografts. Anticancer Drugs 24:599–608PubMedGoogle Scholar
  29. 29.
    Ang K, Zhang Q, Wheeler RH et al (2010) A phase III trial (RTOG 0129) of two radiation-cisplatin regimens for head and neck carcinomas (HNC): impact of radiation and cisplatin intensity on outcome. J Clin Oncol 28:422sGoogle Scholar
  30. 30.
    Sharma A, Mohanti BK, Thakar A et al (2010) Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial. Ann Oncol 21:2272CrossRefPubMedGoogle Scholar
  31. 31.
    Steinmann D, Cerny B, Karstens JH et al (2009) Chemoradiotherapy with weekly cisplatin 40 mg/m(2) in 103 head-and-neck cancer patients: a cumulative dose-effect analysis. Strahlenther Onkol 185:682–688CrossRefPubMedGoogle Scholar
  32. 32.
    Tao Y, Rezaï K, Brain E et al (2011) A phase I trial combining oral cisplatin (CP Ethypharm) with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma. Radiother Oncol 98:42–47CrossRefPubMedGoogle Scholar
  33. 33.
    Tao Y, Bardet E, Rosine D et al (2013) Phase I trial of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma – GORTEC 2004-02. Radiat Oncol Feb 27;8:40PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Gregoire V, Hamoir M, Chen C et al (2011) Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, randomized, double-blind, placebo-controlled study. Radiother Oncol 100:62–69CrossRefPubMedGoogle Scholar
  35. 35.
    Martins RG, Parvathaneni U, Bauman JE et al (2013) Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomized phase II trial. J Clin Oncol 31:1415–1421CrossRefPubMedGoogle Scholar
  36. 36.
    Giralt J (2012) A phase II, randomized trial (CONCERT-1) of chemoradiotherapy (CRT) with or without panitumumab (pmab) in patients (pts) with unresected, locally advanced squamous cell carcinoma of the head and neck (LASCCHN). J Clin Oncol (Suppl; Abstr 5502)Google Scholar
  37. 37.
    Gillison ML, Zhang Q, Jordan R et al (2012) Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol 30(17)2102–2111PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Antonin Levy
    • 1
  • Pierre Blanchard
    • 1
  • Sara Bellefqih
    • 1
  • Nacéra Brahimi
    • 1
  • Joël Guigay
    • 2
  • François Janot
    • 3
  • Stéphane Temam
    • 3
  • Jean Bourhis
    • 1
    • 4
  • Eric Deutsch
    • 1
  • Nicolas Daly-Schveitzer
    • 1
  • Yungan Tao
    • 1
  1. 1.Department of Radiation OncologyGustave RoussyVillejuifFrance
  2. 2.Department of Medical OncologyGustave RoussyVillejuifFrance
  3. 3.Department of Head and Neck SurgeryGustave RoussyVillejuifFrance
  4. 4.Department of Radiation OncologyUniversity Hospital LausanneLausanneSwitzerland

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