Localized Delivery of Cisplatin to Cervical Cancer Improves Its Therapeutic Efficacy and Minimizes Its Side Effect Profile

Overview

Journal Int J Radiat Oncol Biol Phys

Specialties Oncology
Radiology

Date 2020 Nov 30

PMID 33253820

Citations 27

Authors

Cinzia Federico

Jennifer Sun

Barbara Muz

Kinan Alhallak

Pippa F Cosper

Naoshad Muhammad

Amanda Jeske

Amanda Hinger

Stephanie Markovina

Perry Grigsby

Julie K Schwarz

Abdel Kareem Azab

Affiliations

Soon will be listed here.

Abstract

Purpose: Cervical cancer represents the fourth most frequent malignancy in the world among women, and mortality has remained stable for the past 4 decades. Intravenous cisplatin with concurrent radiation therapy is the standard-of-care for patients with local and regional cervical cancer. However, cisplatin induces serious dose-limiting systemic toxicities and recurrence frequently occurs. In this study, we aimed to develop an intracervical drug delivery system that allows cisplatin release directly into the tumor and minimize systemic side effects.

Methods And Materials: Twenty patient biopsies and 5 cell lines treated with cisplatin were analyzed for platinum content using inductively coupled plasma mass spectrometry. Polymeric implants loaded with cisplatin were developed and evaluated for degradation and drug release. The effect of local or systemic cisplatin delivery on drug biodistribution as well as tumor burden were evaluated in vivo, in combination with radiation therapy.

Results: Platinum levels in patient biopsies were 6-fold lower than the levels needed for efficacy and radiosensitization in vitro. Cisplatin local delivery implant remarkably improved drug specificity to the tumor and significantly decreased accumulation in the blood, kidney, and other distant normal organs, compared with traditional systemic delivery. The localized treatment further resulted in complete inhibition of tumor growth.

Conclusions: The current standard-of-care systemic administration of cisplatin provides a subtherapeutic dose. We developed a polymeric drug delivery system that delivered high doses of cisplatin directly into the cervical tumor, while lowering drug accumulation and consequent side effects in normal tissues. Moving forward, these data will be used as the basis of a future first-in-human clinical trial to test the efficacy of localized cisplatin as adjuvant or neoadjuvant chemotherapy in local and regional cervical cancer.

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