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

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