Elsevier

Radiotherapy and Oncology

Volume 50, Issue 2, 1 February 1999, Pages 215-223
Radiotherapy and Oncology

Radiosensitization by intratumoral administration of cisplatin in a sustained-release drug delivery system

https://doi.org/10.1016/S0167-8140(98)00134-0Get rights and content
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Abstract

Purpose: Effects of combining local irradiation and intratumoral (i.t.) administration of cisplatin (CDDP) in a sustained-release drug delivery system (epi gel) were studied in a murine SCCVII squamous cell carcinoma model in mice.

Materials and methods: The epinephrine injectable gel was used as a drug delivery system. Intratumoral pharmacokinetics of CDDP was studied by using 195mPt-CDDP. The tumor volume quadrupling time (TVQT) and tumor growth delay (TGD) time were used to evaluate the antitumor efficacy of treatment regimens.

Results: The concentration and residence of 195mPt-CDDP was significantly higher in tumors treated with 195mPt-CDDP/epi gel than in tumors treated with 195mPt CDDP gel or 195mPt-CDDP suspension. Intratumoral administration of CDDP/epi gel (4 mg/kg) produced an average TGD time of 15.5±2.8 days, which was 5.2 – 7.4 times longer than CDDP suspension i.t. or i.p. When combined with a single dose of radiation (10 Gy), i.t. administration of CDDP/epi gel was 2.0 – 3.6-fold as effective as administered i.t. in suspension (39.2±4.1 vs. 19.8±3.9 days of TGD, P<0.05) or i.p. in solution (39.2±4.1 vs. 11.0±1.6 days, P<0.001) in inhibiting tumor growth and produced 20–60% complete remission of tumors. When combined with fractionated irradiation, pre-irradiation CDDP administration was more effective than post-radiation administration (26.7 vs. 12.1 days of TGD, P<0.05). Mice treated with CDDP/epi gel i.t. alone or in combination with irradiation, had little systemic toxicity.

Conclusions: Intratumoral administration of CDDP using the sustained-release drug delivery system is an efficient and safe method to maximize the drug concentration in tumor, minimize the systemic toxicity and enhance antitumor efficacy of irradiation.

Keywords

Radiation
Injectable gel
Cisplatin
Epinephrine
195mPt
Antitumor efficacy
SCCVII tumor

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