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: 11 x 4.5 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.
Budach
Wilfried
W
Department of Radiation Oncology, University of Tuebingen, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany. wilfried.budach@med.uni-tuebingen.de
Paulsen
F
F
Welz
S
S
Classen
J
J
Scheithauer
H
H
Marini
P
P
Belka
C
C
Bamberg
M
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use*; D017785:Photons; D013534:Survival; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016685:Mitomycin