title: CYP39A1 polymorphism is associated with toxicity during intensive induction chemotherapy in patients with advanced head and neck cancer.
abstract: BACKGROUND
  Induction chemotherapy incorporating docetaxel, cisplatin and 5- fluorouracil before radiotherapy may improve the outcome of patients with advanced head and neck cancer. Nevertheless, the addition of docetaxel increases hematological toxicity and infectious complications. Therefore, genetic markers predicting toxicity and efficacy of this treatment regimen may help to identify patients, who would have the most benefit from this intensive treatment.
  
  
  METHODS
  A cohort of 78 patients with advanced head and neck cancer treated with induction chemotherapy was assessed for clinical outcome and toxicity during treatment with curative intention. Genetic polymorphisms primary associated with treatment efficacy (ERCC2-rs13181, rs1799793, ERCC1-rs3212986, rs11615, XRCC1-rs25487) or with docetaxel caused toxicity (CYP39A1-rs7761731, SLCO1B3-rs11045585) were evaluated in all patients. The results of these analyses were correlated with the clinical outcome of the patients (loco regional control, progression free survival, overall survival) and treatment related toxicity during induction chemotherapy.
  
  
  RESULTS
  Median progression free survival and overall survival was 20 and 31 months in an intention to treat analysis, respectively. Overall response rate to induction chemotherapy was high with 78.1 % of all patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. Genotype A of the CYP39A1 rs7761731 polymorphism was associated with a higher incidence of leucopenia and infections or death during induction chemotherapy.
  
  
  CONCLUSIONS
  Intensive induction chemotherapy results in a high response rate in the majority of patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. The CYP39A1 polymorphism rs7761731 may help to identify patients at high risk for treatment related toxicity.
authors.affiliation: Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.melchardt@salk.at.|Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.melchardt@salk.at.|Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.melchardt@salk.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Melchardt
authors.affiliation: Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. cl.hufnagl@salk.at.|Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. cl.hufnagl@salk.at.|Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. cl.hufnagl@salk.at.
authors.forename: Clemens
authors.initials: C
authors.lastname: Hufnagl
authors.affiliation: Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.magnes@salk.at.|Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.magnes@salk.at.|Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.magnes@salk.at.
authors.forename: Teresa
authors.initials: T
authors.lastname: Magnes
authors.affiliation: Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. lu.weiss@salk.at.|Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. lu.weiss@salk.at.|Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. lu.weiss@salk.at.
authors.forename: Lukas
authors.initials: L
authors.lastname: Weiss
authors.affiliation: Institute of Pathology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. g.hutarew@salk.at.
authors.forename: Georg
authors.initials: G
authors.lastname: Hutarew
authors.affiliation: Institute of Pathology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. d.neureiter@salk.at.
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.affiliation: Institute of Radiology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.schlattau@salk.at.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schlattau
authors.affiliation: Department of Otorhinolaryngology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. g.moser@salk.at.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Moser
authors.affiliation: Department of Oral and Maxillofacial Surgery, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.gaggl@salk.at.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gaggl
authors.affiliation: Institute of Pathology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. w.traenkenschuh@salk.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tränkenschuh
authors.affiliation: Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. r.greil@salk.at.|Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. r.greil@salk.at.|Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. r.greil@salk.at.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.affiliation: Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.egle@salk.at.|Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.egle@salk.at.|Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.egle@salk.at.
authors.forename: Alexander
authors.initials: A
authors.lastname: Egle
mesh_terms: D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013250:Steroid Hydroxylases / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D013250:Steroid Hydroxylases; C499573:CYP39A1 protein, human; D002945:Cisplatin; D005472:Fluorouracil