Phase I/II trial of local interstitial chemotherapy with arsenic trioxide in patients with newly diagnosed glioma

Dayong Han; Lei Teng; Xiaoxiong Wang; Yunbo Zhen; Xiaofeng Chen; Mingchun Yang; Ming Gao; Guang Yang; Mingyang Han; Ligang Wang; Jiajun Xu; Yue Li; Alina Shumadalova; Shiguang Zhao

doi:10.3389/fneur.2022.1001829

Phase I/II trial of local interstitial chemotherapy with arsenic trioxide in patients with newly diagnosed glioma

Front Neurol. 2022 Aug 30:13:1001829. doi: 10.3389/fneur.2022.1001829. eCollection 2022.

Authors

Dayong Han^{1

2

3}, Lei Teng^{1

2

3}, Xiaoxiong Wang^{1

2

3}, Yunbo Zhen^{1

2

3}, Xiaofeng Chen^{1

2

3}, Mingchun Yang^{1

2

3}, Ming Gao^{1

2

3}, Guang Yang^{1

2

3}, Mingyang Han⁴, Ligang Wang^{1

2

3}, Jiajun Xu^{1

2

3}, Yue Li¹, Alina Shumadalova⁵, Shiguang Zhao^{1

2

3

4}

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Institute of Brain Science, Harbin Medical University, Harbin, China.
³ Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China.
⁴ Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, China.
⁵ Department of General Chemistry, Bashkir State Medical University, Ufa, Russia.

Abstract

Background: Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients.

Objective: The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear.

Methods: All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered via an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed.

Results: No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months.

Conclusion: These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.

Keywords: arsenic trioxide; clinical trial; glioma; interstitial chemotherapy; toxicity.