Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancers

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

“…These data gave indirect evidence that top up irradiations under ambient conditions might have given identical results and that our results are entirely consistent with results of Baumann et al (1994Baumann et al ( , 2001. The dose needed to counteract tumour cell repopulation can be calculated from the CHART (Dische et al, 1997) and V-CHART (Dobrowsky and Naude, 2000) clinical trials. According to these trials repopulation without chemotherapy accounts for approximately 0.4 Gy per day, which is substantially lower than in the tested experimental system, suggesting that the potential clinical benefit derived from the inhibition of repopulation by chemotherapy during radiotherapy might be overestimated by our findings.…”

“…In spite of 15% lower total dose and 1 week longer overall treatment time in the radiation series of the chemo-radiation arm, an absolute survival benefit of 14% (P50.01) was observed for the chemo-radiation arm of the study. The extent of the observed survival benefit is not smaller than in other chemo-radiation trials using identical overall treatment times or accelerated treatments in both study arms (Brizel et al, 1998;Calais et al, 1999;Dobrowsky and Naude, 2000;Jeremic et al, 2000). The question arises whether accelerated radiation schedules are necessary, when simultaneous chemo-radiation is used.…”

“…A significant inhibition of repopulation in normal tissues by MMC should be clinically detectable by an enhanced radiation mucositis and dermatitis. However, in clinical trials on head and neck cancer using MMC, only little or no evidence of enhanced mucosal or dermal side effects was found, whereas locoregional tumour control was considerably increased (Haffty et al, 1997;Dobrowsky and Naude, 2000;Budach et al, 2001). This observation gives indirect evidence that repopulation of normal tissues is clinically not significantly inhibited.…”

“…According to the results of randomized clinical trials (Dische et al, 1997;Dobrowsky and Naude, 2000) the dose needed to counteract tumour cell repopulation accounts for approximately 0.4 Gy per day longer overall treatment time. In experimental human tumour models, it was shown that the repopulation rate is tumour cell line dependent, varying over a wide range between 0.5 -4.6 Gy per day (Trott, 1990;Baumann et al, 1994;Budach et al, 1997).…”

“…Moderately and excessive accelerated radiation schedules have been employed to overcome resistance induced by tumour cell repopulation. These studies gave evidence that one can decrease the total radiation dose in accelerated radiation schedules without compromising local tumour control (Dische et al, 1997;Dobrowsky and Naude, 2000). An improvement of local tumour control was observed only in studies that did not decrease the total radiation dose in the accelerated arm.…”