More efforts for attaining a further improved and suitable administration method of peplomycin (PEP) should be made because we have failed to find effective antitumor drugs than peplomycin, which has however a dose dependent complication of pulmonary fibrosis.
Using two strains of nude mouse-transplantable human oral squamous cell carcinoma, T (moderately differentiated) and 0 (poorly differentiated) tumors, 4 different schedules of PEP administration (i.p.) at a total dose of 0-140mg/kg for 0-14-20 days were assigned, i.e. every 3 days-, every 2 days-, and daily one-shot administration (OA), and continuous administration (CA) with an osmic mini pump.
The growth inhibitory effect of PEP was greater in O tumor than in T tumor. Among groups of mice given the same dose of PEP, the shorter the interval between injections became, the greater the growth suppressive effect was obtained ; the CA showed the most effective growth inhibition, the effect of which was equal to that of every 3 days OA of a two-fold higher dose. This was also demonstrated by the histological findings and the effects on the cell cycle with flowcytometry. The levels of PEP in the serum and tissue were consistently higher in mice given CA than in those given OA.As for complications of PEP, weight loss was minimal in mice of CA, that achieved the highest survival rate among mice given the same dose.
With the histological alterations and level of hydroxyproline, the lung toxicity of PEP was highest in mice given daily OA.
From the results of its potent tumor growth inhibition and minimal side effects, CA is evaluated as the most effective administration method and these data might give more informations for clinical application of CA.
