Weinberg M J, Rauth A M
Physics Division, Ontario Cancer Institute, Toronto, Canada.
Int J Radiat Oncol Biol Phys. 1987 Nov;13(11):1691-9. doi: 10.1016/0360-3016(87)90166-0.
The present investigation describes the effects on a murine squamous cell tumor of combined treatment using radiation and 5-Fluorouracil (5FU), with emphasis on 5FU infusions. The tumor, SCC VII/To, was grown intramuscularly in the hind legs of C3H mice. Radiation was given locally with 100 kVp X rays either alone or in combination with 5FU by i.p. bolus injections or 4-14 day infusions using subcutaneously implanted mini-osmotic pumps. Studies with radiation alone indicated regrowth delay increased with total dose. This increase was less for fractionated than single doses. The effects of 5FU alone were compared using i.p. injections or 4, 7 or 14 day infusions. Tumor response to single i.p. bolus injections or 4 day infusions were not significantly different. Up to total drug doses of 200 mg/kg, 14 day infusions were least effective on regrowth delay, 4 day infusions were intermediate and 7 day infusions were most effective. Above total drug doses of 200 mg/kg, effects of 14 day infusions on regrowth delay increased rapidly. The LD50 for single i.p. bolus injections and 7 day infusions were similar, 230 and a total drug dose of 270 mg/kg, respectively. When a 7 day infusion of 5FU (133 mg/kg) was combined with increasing total radiation doses (1 or 5 fractions), the increase in regrowth delay was additive. Combining a fractionated dose of 5 Gy per day for 5 days (5/5 Gy) with increasing total drug doses of 5FU (single i.p. bolus injections or 4, 7 or 14 day infusions) resulted in regrowth delays that were dependent on the total dose of 5FU. Administering a 133 mg/kg dose of 5FU (via a single i.p. bolus injection or 7 day infusion) starting 2 days before, during, or immediately after 5/5 Gy gave the same regrowth delay, indicating no effect of drug sequencing. In conclusion, the above data indicate that (a) 5FU infusions (greater than 4 days) are more effective than 5FU injections on regrowth delay and (b) combinations of 5FU and radiation, produce an additive tumor response, which occurs independent of mode, schedule, and time of 5FU administration, and is dependent on 5FU total dose.
本研究描述了放疗与5-氟尿嘧啶（5FU）联合治疗对小鼠鳞状细胞肿瘤的影响，重点关注5FU输注情况。肿瘤SCC VII/To在C3H小鼠后腿肌肉内生长。采用100 kVp X射线进行局部放疗，单独使用或与5FU联合使用，5FU通过腹腔推注或使用皮下植入的微型渗透泵进行4 - 14天的输注。单独放疗的研究表明，再生长延迟随总剂量增加而延长。分次剂量的增加幅度小于单次剂量。通过腹腔注射或4、7或14天输注比较了单独使用5FU的效果。单次腹腔推注或4天输注对肿瘤的反应无显著差异。在总药物剂量达200 mg/kg之前时，14天输注对再生长延迟的效果最差，4天输注居中，7天输注最有效。在总药物剂量超过200 mg/kg时，14天输注对再生长延迟的效果迅速增强。单次腹腔推注和7天输注的半数致死剂量（LD50）相似，分别为230和总药物剂量270 mg/kg。当5FU进行7天输注（133 mg/kg）并与递增的总放疗剂量（1次或5次分割）联合使用时，再生长延迟的增加是相加的。将每天5 Gy分5次（5/5 Gy）的分次剂量与递增的5FU总药物剂量（单次腹腔推注或4、7或14天输注）联合使用，导致再生长延迟取决于5FU的总剂量。在5/5 Gy放疗前2天、放疗期间或放疗后立即给予133 mg/kg剂量的5FU（通过单次腹腔推注或7天输注），再生长延迟相同，表示药物给药顺序无影响。总之，上述数据表明：（a）5FU输注（超过4天）在再生长延迟方面比5FU注射更有效；（b）5FU与放疗联合使用产生相加的肿瘤反应，该反应与5FU给药方式、方案和时间无关，且取决于5FU总剂量。
