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

Drug Des Devel Ther. 2015 Nov 26;9:6203-10. doi: 10.2147/DDDT.S81488. eCollection 2015.

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.

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: chemoradiation; cisplatin; head and neck cancer; radiotherapy potentiation.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy / methods
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Radiation-Sensitizing Agents / administration & dosage
  • Radiation-Sensitizing Agents / adverse effects
  • Radiation-Sensitizing Agents / therapeutic use
  • Retrospective Studies
  • Survival Rate
  • Young Adult

Substances

  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Cisplatin