Effects of combined treatment with nimustine hydrochloride and radiation on solid FM3A tumor in mice

Female C3H/HeN mice bearing solid FM3A tumors were treated with a combination of ACNU (or Nimustine hydrochloride) and radiation in order to investigate the antitumor effects and also to determine the optimal treatment schedule of ACNU in such combined therapy. ACNU was intravenously injected either twice with an interval of 2 weeks and a dose of 30 mg/kg (intermittent large-dose treatment), or as 4 weekly doses of 15 mg/kg (fractionated small-dose treatment). Local irradiation (5 Gy) at the tumor site was performed twice with an interval of 2 weeks between the doses. Synergistic effects were obtained by the combination of ACNU and radiotherapy in terms of tumor growth inhibition and prolongation of survival. Histology also revealed much greater reduction of viable tumor cells in the case of combination treatment. With either treatment with ACNU alone or in combination with irradiation, the intermittent large-dose injections resulted in better inhibition of tumor growth than did the fractionated small-dose injections, but the survival times with the intermittent treatments were not as prolonged as would be expected from the direct effects. Loss of body weight and depression of WBC number were also much more severe in the intermittent treatment group. Thus, it may be concluded that when ACNU is combined with radiotherapy, the intermittent large-dose regimen is not necessarily superior to the fractionated small-dose one.