Three-weekly Cisplatin versus Weekly Cisplatin Concurrently with Accelerated Radiotherapy Fractionation in Head and Neck Cancers: A Prospective Interventional Study

Introduction: Concurrent chemoradiation is the standard of care for locally advanced head and neck squamous cell carcinoma. Cisplatin remains the primary radiosensitiser, enhancing tumour cell kill through multiple mechanisms. Altered fractionation, combined with concurrent chemotherapy, has demonstrated superior outcomes compared with conventional schedules. Accelerated fractionation is increasingly adopted; however, the optimal concurrent cisplatin schedule remains uncertain. Aim: To compare acute toxicity and early treatment response between three-weekly and weekly cisplatin concurrently with accelerated fractionation in Head and Neck Cancers (HNC). Materials and Methods: The present prospective interventional feasibility study was conducted in the Department of Radiation Oncology, Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, Ambala, Haryana, India. between 1st July 2021 and 30th June 2022. A total of 43 non-metastatic, histopathologically confirmed squamous cell carcinoma patients of the oropharynx, hypopharynx, and larynx (Stage II-IVB) were randomised using computer-based block randomisation into two arms. The three-weekly arm received accelerated radiotherapy (70 Gy in 35 fractions, six fractions per week) with cisplatin 100 mg/m² on days 1 and 22. The weekly arm received the same radiotherapy with cisplatin 40 mg/m² on days 1, 8, 15, 22, 29, and 36. Forty patients were analysed (20 per arm); Toxicities (dermatitis, mucositis, dysphagia, xerostomia, haematologic (using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), renal parameters (using Kidney Disease: Improving Global Outcomes (KDIGO) criteria) and vomiting (using a predefined subjective clinical classification) were assessed and compared between the two arms. Response assessment was done and compared using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. For Quality of Life (QoL) assessment and comparisons, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Head and Neck Module (35 items) (EORTC QLQ-H&N35) questionnaires were used. For comparison, 3-month outcomes were considered. Pearson’s chi-square test was used to compare categorical variables. Continuous variables were compared using the unpaired Student’s t-test. A p-value of <0.05 was considered statistically significant. Results: The mean age of the study population was 54.50±8.4 years (42-70 years), 95% (38 out of 40) of patients were males. All patients in the three-weekly arm received 200 mg/m² cumulative cisplatin, whereas 90% in the weekly arm received >200 mg/m² (p=0.001). Radiotherapy interruptions occurred in 15% versus 5%, respectively. Median Overall Treatment Time (OTT) was similar (40.5 vs 41.5 days; p=0.98). At three months, complete response rates were 65% (three-weekly) and 50% (weekly) (p=0.66). Grade ≥3-mucositis was higher in the three-weekly arm (40% vs 25%; p=0.040). Xerostomia was significantly greater in the three-weekly arm at treatment completion and three months (p<0.05). Conclusion: Both regimens were effective. Weekly cisplatin arm achieved higher cumulative dosing with a more favourable toxicity profile. Although response rates numerically favoured the three-weekly arm, differences were not statistically significant.