A comparison of cisplatin cumulative dose and cisplatin schedule in patients treated with concurrent chemo-radiotherapy in nasopharyngeal carcinoma^✰

Abstract

Introduction:

Three-weekly cisplatin dose is accepted for standard treatment for concurrent chemo-radiotherapy in nasopharyngeal carcinoma. However, different chemotherapy schedules are presented in the literature.

Objective:

We intend to compare toxicity and outcomes of high dose 3-weekly cisplatin versus low dose weekly-cisplatin and cumulative dose of cisplatin in the patients with nasopharyngeal carcinoma.

Methods:

98 patients were included in the study, between 2010 and 2018. Cumulative doses of cisplatin (≥200 mg/m² and <200 mg/m²) and different chemotherapy schedules (weekly and 3-weekly) were compared in terms of toxicity and survival. Besides prognostic factors including age, gender, T category, N category and radiotherapy technique were evaluated in uni-multivariate analysis.

Results:

Median follow-up time 41.5 months (range: 2–93 months). Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 68.9% vs. 90.3% (p = 0.11); 66.2% vs. 81.6% (p = 0.15); 87.3% vs. 95.7% (p = 0.18); 80.1% vs. 76.1% (p = 0.74) for the group treated weekly and 3 weekly, respectively. There was no statistically significant difference between groups. Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 78.2% vs. 49.2% (p = 0.003); 75.8% vs. 47.9% (p = 0.055); 91% vs. 87.1% (p = 0.46); 80% vs. 72.2% (p = 0.46) for the group treated ≥200 mg/m² and <200 mg/m² cumulative dose cisplatin. There was statistically significant difference between groups for overall survival and there was close to being statistically significant difference between groups for local relapse-free survival. Age, gender, T category, N category, chemotherapy schedules were not associated with prognosis in the uni-variety analysis. Radiotherapy technique and cumulative dose of cisplatin was associated with prognosis in uni-variate analysis (HR = 0.21; 95% CI: 0.071–0.628; p = 0.005 and HR = 0.29; 95% CI: 0.125–0.686; p = 0.003, respectively). Only cumulative dose of cisplatin was found as an independent prognostic factor in multivariate analysis (HR = 0.36; 95% CI: 0.146–0.912; p = 0.03). When toxicities were evaluated, such as hematological toxicity, dermatitis, mucositis, nausea and vomiting, there were no statistically significant differences between cumulative dose of cisplatin groups (<200 mg/m² and ≥200 mg/m²) and chemotherapy schedules (3-weekly and weekly). But malnutrition was statistically significant higher in patients treated with 3-weekly cisplatin compared with patients treated with weekly cisplatin (p = 0.001).

Conclusion:

A cisplatin dose with ≥200 mg/m² is an independent prognostic factor for overall survival. Chemotherapy schedules weekly and 3-weekly have similar outcomes and adverse effects. If patients achieve ≥200 mg/m² dose of cumulative cisplatin, weekly chemotherapy schedules may be used safely and effectively in nasopharyngeal carcinoma patients.

KEYWORDS
Cumulative cisplatin dose; Chemotherapy schedule; Nasopharyngeal carcinoma