CTNI-36. THE FEASIBILITY OF USING BORTEZOMIB WITH CHEMOTHERAPY IN ATYPICAL TERATOID/RHABDOID TUMORS

Abstract Atypical teratoid/rhabdoid tumors (ATRTs) are highly aggressive pediatric brain tumors with sensitivity to proteasome inhibitors in preclinical models. We evaluated the feasibility of combining the proteasome inhibitor bortezomib with chemotherapy. Patients aged 0-20 years with newly diagnosed ATRT were enrolled from January 2022 through December 2023. A modified Medical University of Vienna (MUV)-ATRT regimen was used. They were treated with bortezomib of 1.3 mg/m2/dose given intravenously or subcutaneously twice a week for 2 weeks concurrently with 6 cycles of chemotherapy and 2 additional cycles after high-dose chemotherapy. Radiation therapy was given prior to or at the end of chemotherapy. A total of 36 chemotherapy cycles with bortezomib in 6 patients were evaluated. The primary endpoint was grade 3 or higher non-hematologic toxicities. Numbers of cycles with grade 3+ toxicities included: AST/ALT elevation (1), hypokalemia (2), peripheral neuropathy (1), subdural hemorrhage (2), vomiting (2), oral mucositis (3), lung infection (2), urinary tract infection (8), sepsis (3), febrile neutropenia (20). No grade 3+ toxicities were considered bortezomib-related. Three patients completed 8 cycles of bortezomib treatment; 2 patients discontinued the study due to progressive disease after 2 and 4 cycles respectively; 1 patient completed 6 cycles of bortezomib and died of septic shock in complete remission after high-dose chemotherapy. Two patients had a surgical complete resection. Three patients were evaluable for response after bortezomib: 1 partial response and 2 stable disease. Two patients had progression-free survival for 16+ and 22+ months after diagnosis, respectively. Among the 3 patients with progressive disease, 2 had metastatic relapse and 1 had primary and metastatic relapse. There were 4 deaths due to metastatic PD (n=2), septic shock after high-dose chemotherapy (n=1), and septic shock after 2nd line treatment for PD (n=1). We conclude that adding bortezomib to standard and high-dose chemotherapy of ATRT was feasible with the occurrence of grade 3/4 toxicities no more than what was expected with chemotherapy alone. Metastatic relapse remains the major challenge of ATRT treatment.

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Publication Details

Journal
Neuro-Oncology
Published
2024-11-01
DOI
https://doi.org/10.1093/neuonc/noae165.0403
Citations
2
Primary Topic
Chromatin Remodeling and Cancer
Type
article
Field-Weighted Citation Impact
0.47
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article

CTNI-36. THE FEASIBILITY OF USING BORTEZOMIB WITH CHEMOTHERAPY IN ATYPICAL TERATOID/RHABDOID TUMORS

Hsi Chang, Chia‐Chun Kuo, Yu‐Cheng Chou, Jinn-Li Wang et al.
2 citations
Neuro-Oncology
Chromatin Remodeling and Cancer
0.47
article

CTNI-36. THE FEASIBILITY OF USING BORTEZOMIB WITH CHEMOTHERAPY IN ATYPICAL TERATOID/RHABDOID TUMORS

Hsi Chang, Chia‐Chun Kuo, Yu‐Cheng Chou, Jinn-Li Wang, Yi‐Fang Tu, Chu‐Chin Chen, Yi‐Yen Lee, Tzu-Chin Lin, Yu‐Mei Liao, Fang‐Liang Huang, Muh‐Lii Liang, Tai‐Tong Wong, Huy Tran, I‐Rue Lai, Ming‐Jung Chuang, Shiann‐Tarng Jou, Pei‐Chin Lin, Shyh‐Shin Chiou, Ting‐Chi Yeh, Wan‐Ling Ho, Kevin Li‐Chun Hsieh, Shian-Ying Sung, Yen‐Lin Liu, Joon‐Khim Loh, Min‐Lan Tsai, Chao‐Neng Cheng, Shu‐Huey Chen, Ming-Yun Hsieh, Hsin-Lun Lee, Shu‐Mei Chen, Chang-Hsu Chiang, Chia‐Lang Fang, Her-Shyong Shiah, Chia-Yau Chang, Hung‐Wen Yen, Kuo-Sheng Wu, Shih-Chung Wang, James S. Miser
article en
2 citations

Abstract

Abstract Atypical teratoid/rhabdoid tumors (ATRTs) are highly aggressive pediatric brain tumors with sensitivity to proteasome inhibitors in preclinical models. We evaluated the feasibility of combining the proteasome inhibitor bortezomib with chemotherapy. Patients aged 0-20 years with newly diagnosed ATRT were enrolled from January 2022 through December 2023. A modified Medical University of Vienna (MUV)-ATRT regimen was used. They were treated with bortezomib of 1.3 mg/m2/dose given intravenously or subcutaneously twice a week for 2 weeks concurrently with 6 cycles of chemotherapy and 2 additional cycles after high-dose chemotherapy. Radiation therapy was given prior to or at the end of chemotherapy. A total of 36 chemotherapy cycles with bortezomib in 6 patients were evaluated. The primary endpoint was grade 3 or higher non-hematologic toxicities. Numbers of cycles with grade 3+ toxicities included: AST/ALT elevation (1), hypokalemia (2), peripheral neuropathy (1), subdural hemorrhage (2), vomiting (2), oral mucositis (3), lung infection (2), urinary tract infection (8), sepsis (3), febrile neutropenia (20). No grade 3+ toxicities were considered bortezomib-related. Three patients completed 8 cycles of bortezomib treatment; 2 patients discontinued the study due to progressive disease after 2 and 4 cycles respectively; 1 patient completed 6 cycles of bortezomib and died of septic shock in complete remission after high-dose chemotherapy. Two patients had a surgical complete resection. Three patients were evaluable for response after bortezomib: 1 partial response and 2 stable disease. Two patients had progression-free survival for 16+ and 22+ months after diagnosis, respectively. Among the 3 patients with progressive disease, 2 had metastatic relapse and 1 had primary and metastatic relapse. There were 4 deaths due to metastatic PD (n=2), septic shock after high-dose chemotherapy (n=1), and septic shock after 2nd line treatment for PD (n=1). We conclude that adding bortezomib to standard and high-dose chemotherapy of ATRT was feasible with the occurrence of grade 3/4 toxicities no more than what was expected with chemotherapy alone. Metastatic relapse remains the major challenge of ATRT treatment.

Neuro-OncologyVol. 26(Supplement_8)
City Of Hope National Medical Center (US), Taipei Medical University Hospital (TW), University of Medicine and Pharmacy at Ho Chi Minh City (VN), Kaohsiung Medical University Chung-Ho Memorial Hospital (TW), Mackay Memorial Hospital (TW), Taipei Veterans General Hospital (TW), Chang Gung Memorial Hospital (TW), Taichung Veterans General Hospital (TW), Kaohsiung Chang Gung Memorial Hospital (TW), Ministry of Health and Welfare (TW), Buddhist Tzu Chi General Hospital (TW), National Taiwan University Hospital (TW), Wan Fang Hospital (TW), Kaohsiung Veterans General Hospital (TW), National Cheng Kung University Hospital (TW), Changhua Christian Hospital (TW), Taipei Medical University (TW)
Good health and well-being
Openalex Percentile: Top 34%
Chromatin Remodeling and Cancer
0.47
DOIOpen Access PDFOpenAlex
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