title: Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-Based Therapy.
abstract: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%).
  
  
  
  Cabazitaxel is a second-generation taxane that improves the survival of patients with metastatic castrate-resistant prostate cancer following docetaxel therapy. Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. In this randomized phase II trial, we investigated cabazitaxel in patients with recurrent SCCHN.
  
  
  
  Patients with incurable SCCHN with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2for subsequent cycles in the absence of nonhematological adverse events [AEs] greater than grade 2 and hematological AEs greater than grade 3) or methotrexate (40 mg/m2/week). The patients were stratified according to their performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary endpoint was the progression-free survival rate (PFSR) at 18 weeks.
  
  
  
  Of the 101 patients, 53 and 48, with a median age of 58.0 years (range, 41-80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFSR at 18 weeks was 13.2% (95% confidence interval [CI], 5%-25%) for cabazitaxel and 8.3% (95% CI, 2%-20%) for methotrexate. The median progression-free survival was 1.9 months in both arms. The median overall survival was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced serious adverse events with cabazitaxel than with methotrexate (54% vs. 36%). The most common drug-related grade 3-4 AE in the cabazitaxel arm was febrile neutropenia (17.3%).
  
  
  
  This study did not meet its primary endpoint. Cabazitaxel has low activity in recurrent SCCHN.
authors.affiliation: Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium jean-pascal.machiels@uclouvain.be.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
authors.affiliation: Statistical Support Unit, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Van Maanen
authors.affiliation: Department of Medical Oncology, Réseau Hospitalier de Médecine Sociale, Tournai, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Vandenbulcke
authors.affiliation: Department of Medical Oncology, Centre Hospitalier de Jolimont, Haine Saint-Paul, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Filleul
authors.affiliation: Department of Medical Oncology, Centre Hospitalier de Jolimont, Haine Saint-Paul, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Seront
authors.affiliation: Department of Medical Oncology, Centre de Maternité Sainte Elisabeth, Namur, Belgium jean-pascal.machiels@uclouvain.be.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Henry
authors.affiliation: Department of Medical Oncology, CHU Mont-Godinne, Université Catholique de Louvain, Belgium.
authors.forename: Lionel
authors.initials: L
authors.lastname: D'Hondt
authors.affiliation: Department of Medical Oncology, Grand Hôpital de Charleroi, Charleroi, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lonchay
authors.affiliation: Department of Medical Oncology, CHU Ambroise Paré, Mons, Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Holbrechts
authors.affiliation: Department of Medical Oncology Epicura, Baudour, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: Boegner
authors.affiliation: Department of Medical Oncology, Hôpital Civil Marie Curie, Charleroi, Belgium.
authors.forename: Dany
authors.initials: D
authors.lastname: Brohee
authors.affiliation: Department of Head and Neck Surgery, Hôpital Civil Marie Curie, Charleroi, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Dequanter
authors.affiliation: Department of Medical Oncology, Hôpital de la Citadelle, Liège, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Louviaux
authors.affiliation: Department of Medical Oncology, CHU Sart Tilman, Liège, Belgium.
authors.forename: Brieuc
authors.initials: B
authors.lastname: Sautois
authors.affiliation: Department of Medical Oncology, Clinique Saint Pierre Ottignies, Ottignies, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Whenham
authors.affiliation: Department of Medical Oncology, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg.
authors.forename: Guy
authors.initials: G
authors.lastname: Berchem
authors.affiliation: Department of Medical Oncology RHMS-Clinique Louis Caty, Baudour, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vanderschueren
authors.affiliation: Department of Medical Oncology, Free University of Brussels, Brussels, Belgium.
authors.forename: Christel
authors.initials: C
authors.lastname: Fontaine
authors.affiliation: Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schmitz
authors.affiliation: Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Gillain
authors.affiliation: Department of Radiology, Clinique Saint Pierre Ottignies, Ottignies, Belgium.
authors.forename: Joelle
authors.initials: J
authors.lastname: Schoonjans
authors.affiliation: Department of Medical Oncology, University Hospital Ghent, Ghent, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rottey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D000077195:Squamous Cell Carcinoma of Head and Neck; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; C552428:cabazitaxel; D008727:Methotrexate