title: [Prospective double-blind study of prophylaxis of radioxerostomia with Coumarin/Troxerutine in patients with head and neck cancer].
abstract: OBJECTIVE
  Prospective, randomized placebo-controlled double-blind study to prove the efficacy of Coumarin/Troxerutine (Venalot Depot) for protection of salivary glands during a head and neck irradiation.
  
  
  METHODS
  Forty-eight radiotherapy patients (60 Gy) with head and neck cancer were included in this trial. During radiotherapy the salivary glands were located in the core irradiation field. Primary efficacy parameters were sialometry, quantitative salivary gland scintigraphy and clinical evaluation of early effects of radiotherapy (RTOG-score, Table 1). All data were collected at 6 assessments: 1 week pre-radiation (U1), at start (U2), half time (U3) and end (U4) of irradiation, 8 days (U5) and 28 days (U6) after the end of irradiation (Figure 1).
  
  
  RESULTS
  Twenty-three patients (11 verum, 12 placebo) completed the study with all assessments. Sialometrically, all patients were severely (half of radiotherapy) or completely (end of radiotherapy) xerostomatic (Figure 2). In a global efficacy measure according to O'Brien combining scintigraphy and RTOG there was a tendency for a higher efficacy of verum compared to placebo (p = 0.068). After start of irradiation therapy, the RTOG-score showed continuously and significantly lower early radiation effects under verum than under placebo (U3 vs U6: p < 0.05, area under curve: p = 0.032; Table 2, Figure 3). The scintigraphically determined excretion fraction was slightly less impaired in the verum group compared to the placebo treatment (p = 0.12. Figure 4). There was no difference in drug safety between placebo and verum for adverse events, changes in the activity of liver enzymes and for global impression of tolerability.
  
  
  CONCLUSIONS
  The results give support for an advantageous effect of Venalot Depot in the treatment of radiogenic sialadenitis and mucositis. In even a small number of evaluable patients, early clinical effects of irradiation (RTOG-score) were less pronounced in the active treatment group than in the placebo group, but the sample size was too low to prove statistically also the benefit of coumarin/troxerutine with the scintigraphic method. Sialometry seems not suitable for the assessment of early radiation effects.
authors.affiliation: Universitätsklinik für Mund-, Kiefer- und Gesichtschirurgie Mainz. groetz@mkg.klinik.uni-mainz.de
authors.forename: K A
authors.initials: KA
authors.lastname: Grötz
authors.forename: H H
authors.initials: HH
authors.lastname: Henneicke-von Zepelin
authors.forename: R
authors.initials: R
authors.lastname: Kohnen
authors.forename: B
authors.initials: B
authors.lastname: al-Nawas
authors.forename: A
authors.initials: A
authors.lastname: Bockisch
authors.forename: J
authors.initials: J
authors.lastname: Kutzner
authors.forename: P
authors.initials: P
authors.lastname: Wüstenberg
authors.forename: B
authors.initials: B
authors.lastname: Naser-Hijazi
authors.forename: G G
authors.initials: GG
authors.lastname: Belz
authors.forename: W
authors.initials: W
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000368:Aged; D003374:Coumarins / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000528:radiation effects; D011446:Prospective Studies; D011832:Radiation Injuries / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011878:Radiotherapy / Q000009:adverse effects; D012472:Salivation / Q000528:radiation effects; D016896:Treatment Outcome; D014987:Xerostomia / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*
chemical_list: D003374:Coumarins; D006896:Hydroxyethylrutoside; D011837:Radiation-Protective Agents; C005865:troxerutin; C030123:coumarin