A Multicenter Phase II Trial of Nimustine Hydrochloride Administered via Convection-Enhanced Delivery in Children With DIPG.

in Cancer science by Ryuta Saito, Masayuki Kanamori, Yoshiki Arakawa, Yohei Mineharu, Yasuo Aihara, Kentaro Chiba, Toshihiro Kumabe, Ichiyo Shibahara, Yukihiko Sonoda, Kenichiro Matsuda, Manabu Kinoshita, Aya Sato, Fumiaki Takahashi, Teiji Tominaga

TLDR

  • The study found that CED of ACNU after radiotherapy resulted in a 1-year survival rate of 60% and a median survival time of 15 months in children with DIPG.
  • The study suggests that CED of ACNU may be an effective therapeutic strategy for children with DIPG, warranting further development and investigation.
  • The study has important implications for the treatment of DIPG, a fatal and treatment-resistant pediatric malignant tumor.

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a very challenging-to-treat pediatric malignant tumor, with a median survival time of < 12 months. Convection-enhanced delivery (CED) allows for direct drug administration into the tumor site, showing potential as a novel therapeutic approach. This study evaluated the efficacy of CED of nimustine hydrochloride (ACNU) in children with DIPG. This phase 2, single-arm, multicenter study enrolled patients aged 3-21 years and diagnosed with DIPG. The investigational treatment commenced 1 month after completing radiotherapy (local 50-60 Gy). The treatment involved stereotactic brain surgery for catheter placement, followed by ACNU administration via a CED catheter at a concentration of 0.75 mg/mL for 2-3 days until a cumulative dose of 7 (±0.3) mL was achieved. The primary endpoint was the 1-year survival rate. From April 2018 to March 2020, 21 children were enrolled in the trial and treated, with 20 evaluable for the primary endpoint. The 1-year survival rate from the start of radiotherapy was 60%, and the median survival time was 15 months. The response rate was analyzed in 20 patients, with one complete response (CR), six partial responses (PR), nine stable diseases, and four progressive diseases, resulting in a response rate of 35% (CR + PR). The CED of ACNU in the brainstem of children with DIPG after radiotherapy appears to be an effective therapeutic strategy. This approach warrants further development as a treatment for children with DIPG. This study is registered with jRCT (No. jRCT2021190003).

Overview

  • The study evaluated the efficacy of convection-enhanced delivery (CED) of nimustine hydrochloride (ACNU) in children with diffuse intrinsic pontine glioma (DIPG).
  • The study was a phase 2, single-arm, multicenter trial enrolling patients aged 3-21 years with DIPG who had completed radiotherapy.
  • The primary endpoint was the 1-year survival rate, and the study aimed to assess the safety and efficacy of CED of ACNU in DIPG.

Comparative Analysis & Findings

  • The study found a 1-year survival rate of 60% and a median survival time of 15 months in children with DIPG treated with CED of ACNU.
  • The response rate was analyzed in 20 patients, with one complete response (CR), six partial responses (PR), and nine stable diseases, resulting in a response rate of 35% (CR + PR).
  • CED of ACNU after radiotherapy appears to be an effective therapeutic strategy for children with DIPG.

Implications and Future Directions

  • The study warrants further development as a treatment for children with DIPG, offering a novel therapeutic approach for this challenging-to-treat pediatric malignant tumor.
  • Future studies should aim to improve treatment protocols, expand the patient population, and explore the combination of CED with other therapeutic agents.
  • The lack of a control group in this study highlights the need for future studies to include a control group to better understand the efficacy of CED of ACNU compared to alternative treatments for DIPG.
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