TPS265^ Docetaxel, cisplatin (TP), and radiation with or without cetuximab in advanced larynx carcinoma (DeLOS II trial)
A. Dietz, M. Flentje, R. Hagen, R. D. Kortmann, G. Hildebrand, F. Hoppe, I. Schwienhorst, U. Keilholz
Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany Abstract
Background: The DeLOS II trial is a German multicenter (25 centers) randomized phase II trial investigating a
Primary Outcome Measures:
SAE-Reporting April 2009 for decision making Amendment II (red: deaths) docetaxel/cisplatin/5-fluorouracil (TPF) induction chemotherapy with or without cetuximab for patients with only by laryngectomy Confirmatory proof of an adequate survival rate with a functionally larynx- operable carcinoma of the larynx/hypopharynx, followed by radiotherapy. The goal is to preserve a functional larynx. conserving 2 years after randomisation [time frame: LFS-rate 2 years after Methods: Arm A: standard TPF (TP since Aug 2009). Radiation start in week 11; Arm B: Same treatment as arm A with the
addition of cetuximab day 1 400 mg/m2 i.v. followed by weekly 250 mg/m2 i.v. for 16 weeks. Patients with no response after 4 Secondary Outcome Measures:
weeks (first cycle) receive laryngectomy. Planned accrual is 85 patients per treatment arm (170 total). Descriptive analysis of the study arms concerning the secondary end Primary Outcome Measures: Confirmatory proof of an adequate survival rate with a functionally larynx-conserving 2 years after
criteria of the study [time frame: LSF 2 years after randomisation] Explorative comparison of the study arms concerning the primary and Current follow up: Total enrollment in January 2010 was 78 patients. Due to four toxic deaths among the first 62 treated patients
secondary end criteria of the study [time frame: LSF 2 years after (3 in arm A and 1 in arm B), 5-FU was omitted from the induction chemotherapy, and accrual continues with TP with or without cetuximab + radiation due to 4 TPF-related toxic deaths. TPF with or without cetuximab is an effective, albeit toxic induction chemotherapy regimen for patients with SCC of the larynx. SCC of the larynx is often associated with a history of excessive smoking and the expected comorbidities, which may explain the degree of toxicity, which is unacceptable for operable carcinoma • Estimated primary completion date: July 2013 (Final data collection date patients. TP with or without cetuximab may be an alternative for patients, to whom induction-chemotherapy followed by radiation is Inclusion Criteria:
Ages Eligible for Study: 18 Years to 75 Years • Histologically confirmed, primary only with laryngectomy respectable squamous-cell carcinoma of the larynx or TPF (1 cycle)
• T2-T4a carcinoma of the supraglottic, only controllable by laryngectomy and if applicable by root of tongue segmental Series of a 63 years old male patient suffering from T3
• T2-T4a carcinoma of the hypopharynx only controllable by laryngectomy (for example T2, post cricoidal) and hypopharyngeal carcinoma pre, intra and post theray,
• N-status: cervical metastases (N0-N3) have to be rehabilitate by surgical procedures DeLOS-II-protocol before Amendment II (good
• Blood count: Leukocytes >3500/mm\3, Neutrophils > 1500/ mm\3, Thrombocytes > 8000/ mm\3 responder; yellow circle: tumor)
• adequate renal function, defined by serum creatinine and urea not higher than 25% upper NL, creatinine-clearance > TPF (1 cycle)
TPF (2 cycles)
Video endoscopic respiration/phonation vocal cord position
• adequate hepatic function with SGOT, SGPT not higher than 50% and bilirubin not higher than upper NL • anesthetic risk normal or low-grade elevated Cetuximab
• effective contraception after individual advice for men and women if there is a possibility of reproductive potential (effective contraception are: oral contraception with estrogen and gestagen (no minipill), vaginal ring, contraception patch, estrogen free ovulation suppressors, hormone spiral with progesterone, injection for three month with depot gestagen, hormone releasing implantation (luteal hormone containing rod), abstinence or Amendment 1 (01.08.2008 PEI)
Before start of TPF prophylactic antibiotic treatment (Clindamycin) is mandatory. Strong introduction to the patients that immediate presentation at the hospital if fever >38°C occurs after demission. If enteritis clostridium difficile testing should be performed to exclude candidates for TP (1 cycle)
Amendment 2 (08.07.2009 PEI)
Due to four toxic deaths among the first 62 patients (3 in arm A and 1 in arm B), 5FU was omitted from the induction chemotherapy, and accrual continues with TP with or without cetuximab + TP (1 cycle)
radiation. The decission of the data safety board was based on the well known 5FU toxicity causing TP (2 cycles)
vessle damage. Even in head and neck cancer patients with tobacco related high vessle morbidity additional damage of vessles coud be responsible for fatal conditions.
B Initial dose, 400 mg/m2 PR
Amendment 3 (immediate change effective since 18.09.2009, amendment 3 05.2010 PEI)
Prophylactic Clindamycin was substituted by Levofloxacin. In case of resorption disorders hospitalisation while induction chemo therapy is mandatory. Corresponding Author: Andreas Dietz, MD, PhD
Head of the Department of Otorhinolaryngology, Head and Neck Surgery, University
of Leipzig, Liebigstraße 10-14, D-04103 Leipzig


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