Mitomycin C in combination with radiotherapy as a potent inhibitor of tumour cell repopulation in a human squamous cell carcinoma

The potential of Mitomycin C in combination with fractionated irradiation to inhibit tumour cell repopulation of a fast growing squamous cell carcinoma after fractionated radiotherapy was investigated in vivo. A rapidly growing human squamous cell carcinoma (FaDU(dd)) was used for the study. For experiments. NMRI (nu/nu) mice with subcutaneously growing tumours were randomly allocated to no treatment, Mitomycin C, fractionated irradiation (ambient: 11x4.5 Gy in 15 days), or fractionated irradiation combined with Mitomycin C, Graded top up doses (clamped blood flow: 0 - 57 Gy) were given at day 16, 23, 30 or 37. End point of the study was the time to local tumour progression. Data were examined by multiple regression analysis (Cox). Mitomycin C alone resulted in a median time to local tumour progression of 23 (95% confidence limits 17 - 43) days, fractionated irradiation in 31 (25-35) days and combined Mitomycin C plus fractionated irradiation in 65 (58-73) days (P=0.02). Mitomycin C decreased the relative risk of local recurrence by 94% (P< <0.001) equivalent to 31.7 Gy top up dose. Repopulation accounted for 1.33 (0.95 - 1.72) Gy per day top up dose after fractionated irradiation alone and for 0.68 (0.13 - 1.22) Gy per day after fractionated irradiation+Mitomycin C (P=0.018). Mitomycin C significantly reduces the risk of local recurrence and inhibits tumour cell repopulation in combination with fractionated irradiation in vivo in the tested tumour model.