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

Br J Cancer. 2002 Feb 1;86(3):470-6. doi: 10.1038/sj.bjc.6600081.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / radiotherapy
  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Combined Modality Therapy
  • Humans
  • Hypopharyngeal Neoplasms / drug therapy
  • Hypopharyngeal Neoplasms / pathology*
  • Hypopharyngeal Neoplasms / radiotherapy
  • Kinetics
  • Mice
  • Mice, Nude
  • Mitomycin / therapeutic use*
  • Photons
  • Survival
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Mitomycin