title: 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).
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/m(2) paclitaxel, 100 mg/m(2) 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.
authors.affiliation: Department of Otolaryngology, University of Leipzig, Germany. andreas.dietz@medizin.uni-leipzig.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Dietz
authors.forename: Volker
authors.initials: V
authors.lastname: Rudat
authors.forename: Jens
authors.initials: J
authors.lastname: Dreyhaupt
authors.forename: Maria
authors.initials: M
authors.lastname: Pritsch
authors.forename: Florian
authors.initials: F
authors.lastname: Hoppe
authors.forename: Rudolph
authors.initials: R
authors.lastname: Hagen
authors.forename: Leo
authors.initials: L
authors.lastname: Pfreundner
authors.forename: Ursula
authors.initials: U
authors.lastname: Schröder
authors.forename: Hans
authors.initials: H
authors.lastname: Eckel
authors.forename: Markus
authors.initials: M
authors.lastname: Hess
authors.forename: Michael
authors.initials: M
authors.lastname: Schröder
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.forename: Bünzel
authors.initials: B
authors.lastname: Jens
authors.forename: Hans P
authors.initials: HP
authors.lastname: Zenner
authors.forename: Jochen A
authors.initials: JA
authors.lastname: Werner
authors.forename: Rita
authors.initials: R
authors.lastname: Engenhardt-Cabillic
authors.forename: Bernhard
authors.initials: B
authors.lastname: Vanselow
authors.forename: Peter
authors.initials: P
authors.lastname: Plinkert
authors.forename: Marcus
authors.initials: M
authors.lastname: Niewald
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuhnt
authors.forename: Wilfried
authors.initials: W
authors.lastname: Budach
authors.forename: Michael
authors.initials: M
authors.lastname: Flentje
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D007830:Larynx / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel; D002945:Cisplatin