通过瘤内注射顺铂增强放射治疗的效果。

The potentiation of the effect of radiation treatment by intratumoral delivery of cisplatin.

作者信息

Yapp D T, Lloyd D K, Zhu J, Lehnert S M

机构信息

Department of Oncology, McGill University, Montreal, Québec, Canada.

出版信息

Int J Radiat Oncol Biol Phys. 1998 Sep 1;42(2):413-20. doi: 10.1016/s0360-3016(98)00236-3.

DOI:10.1016/s0360-3016(98)00236-3

PMID:9788424

Abstract

PURPOSE

To compare potentiation of the effects of acute or fractionated radiation by cisplatin when the drug was delivered intratumorally by implanted biodegradable polymer, by intraperitoneal injection, or by intraperitoneal osmotic pump.

METHODS AND MATERIALS

Radiation was delivered to a mouse tumor (RIF-1) either in a single dose or in a fractionated regime in conjunction with cisplatin delivered either as a bolus injection, with an osmotic pump, or with a biodegradable polymer rod containing cisplatin. The osmotic pump was implanted in the intraperitoneal cavity of the mouse while the polymer implants were placed directly in the tumor. As the polymer degrades, the drug is released at the treatment site leading to high local concentrations. The osmotic pump, in contrast, leads to prolonged systemic exposure to the drug at low concentrations. Tumor growth delay (TGD) was used as an endpoint in these experiments.

RESULTS

The most effective treatment protocol, in terms of potentiating the effects of radiation was cisplatin delivered by polymer implanted 2 days before an acute dose of radiation (growth modification factor [DMF] = 2.2). Comparison of single and multifraction regimes where polymer implant was on the same day as the commencement of treatment showed greater potentiation of the effect of fractionated than of acute radiation treatment with the DMF for fractionated treatment remaining relatively constant (1.5-1.9) for 5, 8, and 12 fraction treatments. Cisplatin delivered via the osmotic pump did not deliver a high enough dose of cisplatin to produce therapeutic effect in this mouse tumor model and had little impact on response to treatment.

CONCLUSIONS

Our results indicated that cisplatin delivered intratumorally by biodegradable polymer implant was effective in potentiating the effect of both acute and fractionated radiation. For the fractionated treatments the effect was maintained with increasing fraction numbers and treatment time.

摘要

目的

比较当顺铂通过植入的可生物降解聚合物进行瘤内给药、腹腔注射或腹腔渗透泵给药时，其对急性或分次放疗效果的增强作用。

方法与材料

对小鼠肿瘤（RIF-1）进行单次或分次放疗，同时顺铂分别通过大剂量注射、渗透泵或含顺铂的可生物降解聚合物棒给药。渗透泵植入小鼠腹腔，而聚合物植入物直接置于肿瘤内。随着聚合物降解，药物在治疗部位释放，导致局部高浓度。相比之下，渗透泵导致药物在低浓度下长时间全身暴露。在这些实验中，肿瘤生长延迟（TGD）用作终点指标。

结果

就增强放疗效果而言，最有效的治疗方案是在急性放疗剂量前2天通过聚合物植入顺铂（生长修正因子[DMF]=2.2）。聚合物植入与治疗开始在同一天的单次和分次放疗方案比较显示，分次放疗的效果增强作用大于急性放疗，分次治疗的DMF在5次、8次和12次分次治疗中保持相对恒定（1.5 - 1.9）。通过渗透泵给药的顺铂未能在该小鼠肿瘤模型中提供足够高的剂量以产生治疗效果，并且对治疗反应影响很小。