ArticleBlood advances2018
A phase 1 trial evaluating thioridazine in combination with cytarabine in patients with acute myeloid leukemia.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02096289 (A Phase I Trial Evaluating Oral Thioridazine in Combination With Intermediate Dose Cytarabine in Patients 55 Years and Older With Acute Myeloid Leukemia Who Have Relapsed or Have Refractory Disease), which is not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Trial Evaluating Oral Thioridazine in Combination With Intermediate Dose Cytarabine in Patients 55 Years and Older With Acute Myeloid Leukemia Who Have Relapsed or Have Refractory Disease
Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
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- Drug repositioning: examining antipsychotic drugs and their anticancer effects.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2025Review
- Editorial: Drug repurposing for cancer treatment: current and future directions.Frontiers in oncology · 2025Article
- Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning.Frontiers in pharmacology · 2024Review
- First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations.International journal of molecular sciences · 2023Review
- Application of Drug Repurposing-Based Precision Medicine Platform for Leukaemia Patient Treatment.Advances in experimental medicine and biology · 2023Review
- The anti-cancer efficacy of a novel phenothiazine derivative is independent of dopamine and serotonin receptor inhibition.Frontiers in oncology · 2023Article
- Targeting the integrated stress response in hematologic malignancies.Experimental hematology & oncology · 2022Review
- Targeting CaLife (Basel, Switzerland) · 2022Article
- Understanding the role of dopamine in cancer: past, present and future.Carcinogenesis · 2022Review
- Acute Myeloid Leukemia Stem Cells: Origin, Characteristics, and Clinical Implications.Stem cell reviews and reports · 2022Review
- Repurposing Antipsychotics for Cancer Treatment.Biomedicines · 2021Review
- Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.Cell chemical biology · 2021Article
- Article
- Inhibition of Autophagy Enhances the Antitumor Effect of Thioridazine in Acute Lymphoblastic Leukemia Cells.Life (Basel, Switzerland) · 2021Article
- Abnormal dopamine receptor signaling allows selective therapeutic targeting of neoplastic progenitors in AML patients.Cell reports. Medicine · 2021Article
- ONC201 and imipridones: Anti-cancer compounds with clinical efficacy.Neoplasia (New York, N.Y.) · 2020Review
- Thioridazine requires calcium influx to induce MLL-AF6-rearranged AML cell death.Blood advances · 2020Article
- Inhibition of Fatty Acid Oxidation as a New Target To Treat Primary Amoebic Meningoencephalitis.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
We completed a phase 1 dose-escalation trial to evaluate the safety of a dopamine receptor D2 (DRD2) antagonist thioridazine (TDZ), in combination with cytarabine. Thirteen patients 55 years and older with relapsed or refractory acute myeloid leukemia (AML) were enrolled. Oral TDZ was administered at 3 dose levels: 25 mg (n = 6), 50 mg (n = 4), or 100 mg (n = 3) every 6 hours for 21 days. Intermediate-dose cytarabine was administered on days 6 to 10. Dose-limiting toxicities (DLTs) included grade 3 QTc interval prolongation in 1 patient at 25 mg TDZ and neurological events in 2 patients at 100 mg TDZ (gait disturbance, depressed consciousness, and dizziness). At the 50-mg TDZ dose, the sum of circulating DRD2 antagonist levels approached a concentration of 10 μM, a level noted to be selectively active against human AML in vitro. Eleven of 13 patients completed a 5-day lead-in with TDZ, of which 6 received TDZ with hydroxyurea and 5 received TDZ alone. During this period, 8 patients demonstrated a 19% to 55% reduction in blast levels, whereas 3 patients displayed progressive disease. The extent of blast reduction during this 5-day interval was associated with the expression of the putative TDZ target receptor DRD2 on leukemic cells. These preliminary results suggest that DRD2 represents a potential therapeutic target for AML disease. Future studies are required to corroborate these observations, including the use of modified DRD2 antagonists with improved tolerability in AML patients. This trial was registered at www.clinicaltrials.gov as #NCT02096289.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.