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Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial)

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Abstract

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m2 paclitaxel, 100 mg/m2 cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56–70 Gy in 5.5–7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4–72.2%), after 42 months was 56.5% (95% CI, 44.2–68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9–55.0%); after 42 months, 41.3% (95% CI, 29.3–53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.

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Author information

Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany

    Andreas Dietz

  2. Saad Specialist Hospital, Al Khobar, 31952, Kingdom of Saudi Arabia

    Volker Rudat

  3. Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany

    Jens Dreyhaupt & Maria Pritsch

  4. Department of Otolaryngology, Head and Neck Surgery, City Hospital Oldenburg, Oldenburg, Germany

    Florian Hoppe

  5. Department of Otolaryngology, Head and Neck Surgery, University of Würzburg, Würzburg, Germany

    Rudolph Hagen

  6. Department of Radiation Oncology, University of Würzburg, Würzburg, Germany

    Leo Pfreundner & Michael Flentje

  7. Department of Otolaryngology, Head and Neck Surgery, University of Lübeck, Lübeck, Germany

    Ursula Schröder

  8. Department of Otolaryngology, Head and Neck Surgery, Hospital Klagenfurt, Klagenfurt, Austria

    Hans Eckel

  9. Department of Otolaryngology, Head and Neck Surgery, University of Hamburg, Hamburg, Germany

    Markus Hess

  10. Department of Otolaryngology, Head and Neck Surgery, City Hospital Kassel, Kassel, Germany

    Michael Schröder

  11. Department of Radiation Oncology, City Hospital Kassel, Kassel, Germany

    Petra Schneider

  12. Department of Otolaryngology, Head and Neck Surgery, City Hospital Nordhausen, Nordhausen, Germany

    Bünzel Jens

  13. Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany

    Hans P. Zenner

  14. Department of Otolaryngology, Head and Neck Surgery, University of Marburg, Marburg, Germany

    Jochen A. Werner

  15. Department of Radiation Oncology, University of Marburg, Marburg, Germany

    Rita Engenhardt-Cabillic

  16. Department of Otolaryngology, Head and Neck Surgery, St.Vincentius, Karlsruhe, Germany

    Bernhard Vanselow

  17. Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany

    Peter Plinkert

  18. Department of Radiation Oncology, University of Homburg/Saarland, Homburg/Saarland, Germany

    Marcus Niewald

  19. Department of Radiation Oncology, University of Halle, Halle, Germany

    Thomas Kuhnt

  20. Department of Radiation Oncology, University of Düsseldorf, Düsseldorf, Germany

    Wilfried Budach

  21. Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde/Plastische Operationen, Universität Leipzig, Liebigstrasse 10-14, 04103, Leipzig, Germany

    Andreas Dietz

Authors
  1. Andreas Dietz
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  2. Volker Rudat
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  3. Jens Dreyhaupt
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  4. Maria Pritsch
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  5. Florian Hoppe
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  6. Rudolph Hagen
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  7. Leo Pfreundner
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  8. Ursula Schröder
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  9. Hans Eckel
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  10. Markus Hess
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  11. Michael Schröder
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  12. Petra Schneider
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  13. Bünzel Jens
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  14. Hans P. Zenner
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  15. Jochen A. Werner
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  16. Rita Engenhardt-Cabillic
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  17. Bernhard Vanselow
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  18. Peter Plinkert
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  19. Marcus Niewald
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  20. Thomas Kuhnt
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  21. Wilfried Budach
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  22. Michael Flentje
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Corresponding author

Correspondence to Andreas Dietz.

Additional information

This trial was initiated and conducted by the German Larynx Organ Preservation Study Group (DeLOS) which was founded as collaboration between head and neck surgeons and radiation oncologists to focus on the role of multimodality treatment in advanced laryngeal and hypopharyngeal cancer in Germany.

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Dietz, A., Rudat, V., Dreyhaupt, J. et al. Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial). Eur Arch Otorhinolaryngol 266, 1291–1300 (2009). https://doi.org/10.1007/s00405-008-0846-y

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  • DOI: https://doi.org/10.1007/s00405-008-0846-y

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