title: Radiotherapy potentiation with weekly cisplatin compared to standard every 3 weeks cisplatin chemotherapy for locoregionally advanced head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Despite its toxicity, cisplatin every 3 weeks (q3w) is the standard potentiation of chemo-radiotherapy for head and neck squamous cell carcinoma. This study aimed to determine whether weekly cisplatin (q1w) could be a safe and effective alternative.
  
  
  METHODS
  Two hundred and sixty-two patients with head and neck squamous cell carcinoma, irradiated in our institution with cisplatin (q1w or q3w) between January 2004 and December 2008, were retrospectively included. Overall survival (OS) and progression-free survival (PFS) were evaluated. Survival distributions were estimated by Kaplan-Meier method and compared using the log-rank test. Prognostic effect of chemo-radiotherapy was explored using Cox model.
  
  
  RESULTS
  A total of 165 and 97 patients received q1w and q3w cisplatin, respectively. Median age, stage at diagnosis, alcohol consumption, intensity-modulated radiation therapy use, median weight, and renal failure before radiotherapy were significantly different, showing lower risk in the q3w group. Q3w cisplatin was found to be more toxic in terms of weight loss, renal failure, worse chemotherapy plan completion, and grade 3/4 mucositis and dermatitis, with more patients requiring analgesics, secondary hospitalization, and radiotherapy interruption (≥3 days), and patients affected by long-term toxicities. With a median follow-up of 73 months (95% confidence interval [CI] [68.9-76.2]), OS was found to be significantly better with q3w (5 years OS: 62.3%; 95% CI [51.6-71.3]) than with q1w cisplatin (5 years OS: 52.6%; 95% CI [44.5-60.0]) (log-rank P=0.0146). More number of patients treated according to the q1w schedule experienced a recurrence: 47.3% vs 30.9% (P=0.009). Thus, the PFS for q3w schedule was found to be globally better (5 years PFS: 55.8%; 95% CI [45.0-65.3]) than for q1w schedule (5 years PFS: 43.6%; 95% CI [35.9-51.0]) (log-rank P=0.0161). However, both multivariate analyses, OS and PFS, produce no significant hazard ratio for chemo-radiotherapy modality once adjusted on unbalanced covariates according to the descriptive analysis.
  
  
  CONCLUSIONS
  Though q1w seemed to be safer than q3w according to the descriptive analysis, multivariate analyses failed to conclude about its efficiency. Therefore, we conclude that the q3w schedule should remain the standard and prospective comparisons are needed.
authors.affiliation: Department of Medicine, University of Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Fayette
authors.affiliation: Department of Medicine, University of Lyon, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Molin
authors.affiliation: Biostatistics Unit, University of Lyon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lavergne
authors.affiliation: Department of Radiotherapy, Centre Léon Bérard, University of Lyon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montbarbon
authors.affiliation: Department of Radiotherapy, Centre Léon Bérard, University of Lyon, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Racadot
authors.affiliation: Department of Surgery, Hôpital Croix-Rousse, University of Lyon, Lyon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Poupart
authors.affiliation: Department of Surgery, Hôpital Edouard Herriot, University of Lyon, Lyon, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Ramade
authors.affiliation: Department of Surgery, Centre Léon Bérard, University of Lyon, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Zrounba
authors.affiliation: Department of Surgery, Centre Hospitalier Lyon-Sud, Université de Lyon, Pierre-Bénite, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ceruse
authors.affiliation: Department of Radiotherapy, Centre Léon Bérard, University of Lyon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pommier
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin
keywords: chemoradiation; cisplatin; head and neck cancer; radiotherapy potentiation