Radiotherapy potentiation with weekly cisplatin compared to standard every 3 weeks cisplatin chemotherapy for locoregionally advanced head and neck squamous cell carcinoma 

Abstract

Jérôme Fayette,1 Yann Molin,1 Emilie Lavergne,2 Xavier Montbarbon,3 Séverine Racadot,3 Marc Poupart,4 Antoine Ramade,5 Philippe Zrounba,6 Philippe Ceruse,7 Pascal Pommier31Department of Medicine, 2Biostatistics Unit, 3Department of Radiotherapy, Centre Léon Bérard, University of Lyon, 4Department of Surgery, Hôpital Croix-Rousse, 5Department of Surgery, Hôpital Edouard Herriot, 6Department of Surgery, Centre Léon Bérard, University of Lyon, Lyon, France; 7Department of Surgery, Centre Hospitalier Lyon-Sud, Université de Lyon, Pierre-Bénite, FranceBackground: 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.Patients and 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.Conclusion: 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. Keywords: head and neck cancer, radiotherapy potentiation, chemoradiation, cisplatin