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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/m2/day 1, 5-FU (F) 750 mg/m2/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+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 information

Dietz A1, Wichmann G1, Kuhnt T2, Pfreundner L3, Hagen R4, Scheich M4, Kölbl O5, Hautmann MG5, Strutz J6, Schreiber F7, Bockmühl U7, Schilling V8, Feyer P9, de Wit M10, Maschmeyer G11, Jungehülsing M12, Schroeder U13, Wollenberg B13, Sittel C14, Münter M15, Lenarz T16, Klussmann JP17, Guntinas-Lichius O18, Rudack C19, Eich HT20, Foerg T21, Preyer S22, Westhofen M23, Welkoborsky HJ24, Esser D25, Thurnher D26, Remmert S27, Sudhoff H28, Görner M29, Bünzel J30, Budach V31, Held S32, Knödler M33, Lordick F33, Wiegand S1, Vogel K1, Boehm A34, Flentje M3, Keilholz U35.
1
Department of Otolaryngology, Head and Neck Surgery, University Leipzig, Leipzig, Germany.
2
Department of Radiation Oncology, University Leipzig, Leipzig, Germany.
3
Department of Radiation Oncology, University Würzburg, Würzburg, Germany.
4
Department of Otolaryngology, Head and Neck Surgery, University Würzburg, Würzburg, Germany.
5
Department of Radiation Oncology, University Regensburg, Regensburg, Germany.
6
Department of Otolaryngology, Head and Neck Surgery, University Regensburg, Regensburg, Germany.
7
Department of Otolaryngology, Head and Neck Surgery, Klinikum Kassel, Kassel, Germany.
8
Department of Otolaryngology, Head and Neck Surgery, Vivantes, Berlin, Neukölln, Germany.
9
Department of Radiation Oncology, Vivantes, Berlin, Neukölln, Germany.
10
Department of Hemato-Oncology, Vivantes, Berlin, Neukölln, Germany.
11
Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany.
12
Department of Otolaryngology, Head and Neck Surgery, Potsdam Klinikum, Potsdam, Germany.
13
Department of Otolaryngology, Head and Neck Surgery, University Lübeck, Lübeck, Germany.
14
Department of Otolaryngology, Head and Neck Surgery, Katharinen Hospital, Stuttgart, Germany.
15
Department of Radiation Oncology, Katharinen Hospital, Stuttgart, Germany.
16
Department of Otolaryngology, Head and Neck Surgery, MHH Hannover, Hannover, Germany.
17
Department of Otolaryngology, Head and Neck Surgery, University Gießen, Gießen, Germany.
18
Department of Otolaryngology, Head and Neck Surgery, Jena University Hospital, Jena, Germany.
19
Department of Otolaryngology, Head and Neck Surgery, University Münster, Münster, Germany.
20
Department of Radiation Oncology, University Münster, Münster, Germany.
21
Department of Radiation Oncology, Head and Neck Surgery, St. Vincentius, ViDia Christliche Kliniken Karlsruhe, Karlsruhe, Germany.
22
Department of Otolaryngology, Head and Neck Surgery, St. Vincentius, ViDia Christliche Kliniken Karlsruhe, Karlsruhe, Germany.
23
Department of Otolaryngology, Head and Neck Surgery, University Aachen, Aachen, Germany.
24
Department of Otolaryngology, Head and Neck Surgery, Klinikum Nordstadt, Hannover, Germany.
25
Department of Otolaryngology, Head and Neck Surgery, Helios Klinikum, Erfurt, Germany.
26
Department of Otolaryngology, Head and Neck Surgery, University Graz, Graz, Austria.
27
Department of Otolaryngology, Head and Neck Surgery, Malteser Hospital Duisburg, Duisburg, Germany.
28
Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany.
29
Department of Hemato-Oncology, Klinikum Bielefeld, Bielefeld, Germany.
30
Department of Otolaryngology, Head and Neck Surgery, Klinikum Nordhausen, Nordhausen, Germany.
31
Department of Radiation Oncology, CCC, Charité-University Medicine, Berlin, Germany.
32
ClinAssess GmbH, Leverkusen, Germany.
33
Department of Oncology, University Cancer Center Leipzig (UCCL), Leipzig, Germany.
34
Department of Otolaryngology, Head and Neck Surgery, St. Georg Hospital Leipzig, Leipzig, Germany.
35
Charité Comprehensive Cancer Center, Berlin, Germany.