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The study of investigators indicated that TMZ can up-regulate dopamine D2 receptor (DRD2) expression, and mediates Ferroptosis inhibition and chemoresistance of GBM. The clinical data also proved that the DRD2 expression in recurrent GBM is significantly higher than that in primary GBM. Moreover, the DRD2 antagonist haloperidol can attenuate the above function of DRD2, and increase the sensitivity of GBM to the TMZ by inducing fatal autophagy and ferroptosis. In xenograft mice, the combined usage of haloperidol and Temozolomide (TMZ) can significantly inhibit tumor growth and increase overall survival. The investigators' findings have been published in Clinical cancer research. Haloperidol known as a butylbenzene antipsychotic drug, has been widely used in several kinds of mental illnesses, such as depression, schizophrenia, and Bipolar disorder. And the safe dosage of the haloperidol is clear so far. So in this study, the investigators will recruit the patients who suffered from recurrent GBM, and evaluate the effectiveness of single TMZ chemotherapy or combined with haloperidol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TMZ single | Placebo Comparator | Single oral Temozolomide |
|
| TMZ and Haloperidol | Experimental | Oral Temozolomide and Haloperidol |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Haloperidol Tablets | Drug | Haloperidol tablet 6mg, Oral, Triple/Day |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of partial relief and complete relief | Detected the percentage of partial relief and complete relief according to RANO criteria. | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | Overall survival was evaluated during follow-up period. | One year |
| DRD2 expression | If the recurrent GBM underwent surgery resection, the DRD2 expression was detected. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse drug reaction of haloperidol | Detection the adverse drug reaction of haloperidol | One year |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yuntao Lu, Ph.D | Contact | +86013632101002 | lllu2000yun@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Yuntao Lu, Ph.D | Nanfang Hospital, Southern Medical University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37249604 | Result | Shi L, Chen H, Chen K, Zhong C, Song C, Huang Y, Wang T, Chen L, Li C, Huang A, Qi S, Li H, Lu Y. The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma. Clin Cancer Res. 2023 Aug 15;29(16):3172-3188. doi: 10.1158/1078-0432.CCR-22-3971. |
| Label | URL |
|---|---|
| Our study about the anti-tumor function of Haloperidol, which was published in Clinical Cancer research. | View source |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| D006220 | Haloperidol |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D002090 | Butyrophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
| D003606 | Dacarbazine |
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| Temozolomide |
| Drug |
Temozolomide, 150mg/kg, Oral, Once/Day, 5/28 days |
|
| One year |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D014226 |
| Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |