ENHANCEMENT OF RADIATION RESPONSE BY PACLITAXEL IN MICE ACCORDING TO DIFFERENT TREATMENT SCHEDULES

Purpose: The aim of our study was to determine if paclitaxel could be used as a radiosensitizer in vivo. Materials and methods: Paclitaxel w as tested as a single agent and combined with an X-ray treatment, Pacl itaxel was administered i.p. in doses from 30 to 120 mg/kg b.w. to (C3 D2F1) mice bearing spontaneous mammary carcinoma, Tumor growth delay ( TGD) or tumor control dose (TCD50, radiation dose needed to induce loc al tumor control in 50% of irradiated animals) and moist desquamation dose (MDD50, radiation dose needed to induce serious moist desquamatio n in 50% of the non-tumor-bearing feet) were the endpoints, DNA how cy tometric analysis was performed, Results: DNA analysis demonstrated a G2/M block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h from paclitaxel administration, Administering paclitax el, in graded doses, 15 min before a 10-Gy X-ray treatment resulted in a linear regression line, almost parallel to that with paclitaxel alo ne, with a growth delay of about 6 days, In contrast, varying the X-ra y dose with a constant paclitaxel injection (45 mg/kg b.w.) treatment showed some degree of synergism as the linear regression curves diverg ed, Interval time and sequence between paclitaxel administration and a 10 Gy X-ray treatment did not influence TGD, Protocols with paclitaxe l at 30, 45, or GO mg/kg were combined with radiation treatments at va rious doses (from 10 to 65 Gy), Values of TCD50 varied from 50.8 Gy fo r X-ray alone to 31.8 Gy for paclitaxel 60 mg/kg + X-ray. No differenc es were observed among MDD of different protocols, Conclusions: These results suggest that, under some conditions, paclitaxel combined with radiation can show superadditive effects and this result combined with the lack of severe normal tissue damage indicate that a favorable the rapeutic gain can be obtained. (C) 1998 Elsevier Science Inc.