CHRONOMODULATED CHEMOTHERAPY AND CONCOMITANT RADIOTHERAPY, FOR THE MANAGEMENT OF LOCALLY ADVANCED, HEAD AND NECK SQUAMOUS CELL CARCINOMA

Purpose: To compare the efficacy and toxicity of chronomodulated concomitant chemotherapy using weekly Cisplatin at 0600 hour and 1800 hour along with radical external beam radiotherapy (EBRT) in the management of locally advanced head and neck carcinoma (LAHNC).

Material and method: Previously untreated, histopathologically proven 60 patients of LAHNC (stage III-IVB) were taken for definitive treatment by concurrent chemo-radiation. These patients were randomly assigned (by draw of lots) either of two groups; group I, the 0600 hour cisplatin administration and group II, the 1800 hour cisplatin administration group, each in dose of 30 mg/m². EBRT was given as 66Gy/ 33Fr/ 6.5 weeks on telecobalt machine. Night shift workers were excluded. Response to treatment and toxicity were investigated. Observations were made at the end of treatment and 6 months of follow up.

Results: At the end of treatment, complete tumor response (CR_T) in group II were better (40.0% versus 26.7%) and complete node response (CR_N) were comparable (34.8% versus 34.6%). Acute skin and mucosal reactions (grade 3) were 3.3% versus 10% each. Hematological toxicity: fall in hemoglobin (grade 3) was lesser in group II patients- 3.3% versus 10% in group I, fall in total leukocyte count was observed up to grade 1 only in two patients (6.7%) of each group. Upper gastro-intestinal toxicity was significantly lesser in group II (6.7% versus 26.7%; p= 0.038), also translating to weight loss, (3.3% versus 13.3%; p= 0.161). Disease status at last follows up was as follows: CR_T in group I and II- 70% versus 73.3% and CR_N 70.1% versus 78.3%. Late mucosal reactions were same in two groups (grade I+II, 73.3%). Skin reactions were lesser in group II. None of the patients experienced grade 3 or 4 toxicity.

Conclusion: Administration of cisplatin; in the evening is better compared to morning administration in terms of disease control and toxicity profile; given concurrent with EBRT, for management of LAHNC. A larger study with more groups receiving chemotherapy at frequent intervals (say 6 hours apart) may further establish the very right time of administration of chemotherapy.