Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II

A. Dietz; G. Wichmann; T. Kuhnt; L. Pfreundner; R. Hagen; M. Scheich; O. Kölbl; M. G. Hautmann; J. Strutz; F. Schreiber; U. Bockmühl; V. Schilling; P. Feyer; M. De Wit; G. Maschmeyer; M. Jungehülsing; U. Schroeder; B. Wollenberg; C. Sittel; M. Münter; T. Lenarz; J. P. Klussmann; O. Guntinas-Lichius; C. Rudack; H. T. Eich; T. Foerg; S. Preyer; M. Westhofen; H. J. Welkoborsky; D. Esser; D. Thurnher; S. Remmert; H. Sudhoff; M. Görner; J. Bünzel; V. Budach; S. Held; M. Knödler; F. Lordick; S. Wiegand; K. Vogel; A. Boehm; M. Flentje; U. Keilholz

doi:10.1093/annonc/mdy332

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II

A. Dietz^*, G. Wichmann, T. Kuhnt, L. Pfreundner, R. Hagen, M. Scheich, O. Kölbl, M. G. Hautmann, J. Strutz, F. Schreiber, U. Bockmühl, V. Schilling, P. Feyer, M. De Wit, G. Maschmeyer, M. Jungehülsing, U. Schroeder, B. Wollenberg, C. Sittel, M. MünterT. Lenarz, J. P. Klussmann, O. Guntinas-Lichius, C. Rudack, H. T. Eich, T. Foerg, S. Preyer, M. Westhofen, H. J. Welkoborsky, D. Esser, D. Thurnher, S. Remmert, H. Sudhoff, M. Görner, J. Bünzel, V. Budach, S. Held, M. Knödler, F. Lordick, S. Wiegand, K. Vogel, A. Boehm, M. Flentje, U. Keilholz

^*Korrespondierende/r Autor/-in für diese Arbeit

Klinik für Hals-, Nasen- und Ohrenheilkunde

19 Zitate (Scopus)

Abstract

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m ² /day 1, 5-FU (F) 750 mg/m ² /day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with 30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed ICþRT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

Originalsprache	Englisch
Zeitschrift	Annals of Oncology
Jahrgang	29
Ausgabenummer	10
Seiten (von - bis)	2105-2114
Seitenumfang	10
ISSN	0923-7534
DOIs	https://doi.org/10.1093/annonc/mdy332
Publikationsstatus	Veröffentlicht - 01.10.2018

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Profilbereich: Lübeck Integrated Oncology Network (LION)

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Dietz, A., Wichmann, G., Kuhnt, T., Pfreundner, L., Hagen, R., Scheich, M., Kölbl, O., Hautmann, M. G., Strutz, J., Schreiber, F., Bockmühl, U., Schilling, V., Feyer, P., De Wit, M., Maschmeyer, G., Jungehülsing, M., Schroeder, U., Wollenberg, B., Sittel, C., ... Keilholz, U. (2018). Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II. Annals of Oncology, 29(10), 2105-2114. https://doi.org/10.1093/annonc/mdy332

@article{068b3557c9f544b1a037854198ba63d3,

title = "Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II",

abstract = " Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-na{\"i}ve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m 2 /day 1, 5-FU (F) 750 mg/m 2 /day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with 30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC{\th}RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664. ",

author = "A. Dietz and G. Wichmann and T. Kuhnt and L. Pfreundner and R. Hagen and M. Scheich and O. K{\"o}lbl and Hautmann, {M. G.} and J. Strutz and F. Schreiber and U. Bockm{\"u}hl and V. Schilling and P. Feyer and {De Wit}, M. and G. Maschmeyer and M. Jungeh{\"u}lsing and U. Schroeder and B. Wollenberg and C. Sittel and M. M{\"u}nter and T. Lenarz and Klussmann, {J. P.} and O. Guntinas-Lichius and C. Rudack and Eich, {H. T.} and T. Foerg and S. Preyer and M. Westhofen and Welkoborsky, {H. J.} and D. Esser and D. Thurnher and S. Remmert and H. Sudhoff and M. G{\"o}rner and J. B{\"u}nzel and V. Budach and S. Held and M. Kn{\"o}dler and F. Lordick and S. Wiegand and K. Vogel and A. Boehm and M. Flentje and U. Keilholz",

note = "Funding Information: DeLOS-II was an investigator-initiated trial supported by unrestricted educational grants from Merck, Darmstadt, Germany, and Sanofi, Berlin, Germany. No grant number is applicable. The protocol was developed by the German larynx preservation study group (DeLOS) in cooperation with the Interdisciplinary Head and Neck Study Group (IAG-KHT) of the German Cancer Society (DKG). Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2018",

month = oct,

day = "1",

doi = "10.1093/annonc/mdy332",

language = "English",

volume = "29",

pages = "2105--2114",

journal = "Annals of Oncology",

issn = "0923-7534",

number = "10",

}

Dietz, A, Wichmann, G, Kuhnt, T, Pfreundner, L, Hagen, R, Scheich, M, Kölbl, O, Hautmann, MG, Strutz, J, Schreiber, F, Bockmühl, U, Schilling, V, Feyer, P, De Wit, M, Maschmeyer, G, Jungehülsing, M, Schroeder, U, Wollenberg, B, Sittel, C, Münter, M, Lenarz, T, Klussmann, JP, Guntinas-Lichius, O, Rudack, C, Eich, HT, Foerg, T, Preyer, S, Westhofen, M, Welkoborsky, HJ, Esser, D, Thurnher, D, Remmert, S, Sudhoff, H, Görner, M, Bünzel, J, Budach, V, Held, S, Knödler, M, Lordick, F, Wiegand, S, Vogel, K, Boehm, A, Flentje, M & Keilholz, U 2018, 'Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II', Annals of Oncology, Jg. 29, Nr. 10, S. 2105-2114. https://doi.org/10.1093/annonc/mdy332

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II. / Dietz, A.; Wichmann, G.; Kuhnt, T. et al.
in: Annals of Oncology, Jahrgang 29, Nr. 10, 01.10.2018, S. 2105-2114.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II

AU - Dietz, A.

AU - Wichmann, G.

AU - Kuhnt, T.

AU - Pfreundner, L.

AU - Hagen, R.

AU - Scheich, M.

AU - Kölbl, O.

AU - Hautmann, M. G.

AU - Strutz, J.

AU - Schreiber, F.

AU - Bockmühl, U.

AU - Schilling, V.

AU - Feyer, P.

AU - De Wit, M.

AU - Maschmeyer, G.

AU - Jungehülsing, M.

AU - Schroeder, U.

AU - Wollenberg, B.

AU - Sittel, C.

AU - Münter, M.

AU - Lenarz, T.

AU - Klussmann, J. P.

AU - Guntinas-Lichius, O.

AU - Rudack, C.

AU - Eich, H. T.

AU - Foerg, T.

AU - Preyer, S.

AU - Westhofen, M.

AU - Welkoborsky, H. J.

AU - Esser, D.

AU - Thurnher, D.

AU - Remmert, S.

AU - Sudhoff, H.

AU - Görner, M.

AU - Bünzel, J.

AU - Budach, V.

AU - Held, S.

AU - Knödler, M.

AU - Lordick, F.

AU - Wiegand, S.

AU - Vogel, K.

AU - Boehm, A.

AU - Flentje, M.

AU - Keilholz, U.

N1 - Funding Information: DeLOS-II was an investigator-initiated trial supported by unrestricted educational grants from Merck, Darmstadt, Germany, and Sanofi, Berlin, Germany. No grant number is applicable. The protocol was developed by the German larynx preservation study group (DeLOS) in cooperation with the Interdisciplinary Head and Neck Study Group (IAG-KHT) of the German Cancer Society (DKG). Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m 2 /day 1, 5-FU (F) 750 mg/m 2 /day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with 30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed ICþRT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

AB - Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m 2 /day 1, 5-FU (F) 750 mg/m 2 /day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with 30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed ICþRT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

UR - http://www.scopus.com/inward/record.url?scp=85056422812&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdy332

DO - 10.1093/annonc/mdy332

M3 - Journal articles

C2 - 30412221

AN - SCOPUS:85056422812

SN - 0923-7534

VL - 29

SP - 2105

EP - 2114

JO - Annals of Oncology

JF - Annals of Oncology

IS - 10

ER -

Dietz A, Wichmann G, Kuhnt T, Pfreundner L, Hagen R, Scheich M et al. Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II. Annals of Oncology. 2018 Okt 1;29(10):2105-2114. doi: 10.1093/annonc/mdy332