ArticleAmerican journal of hematology2016
Phase I study of evofosfamide, an investigational hypoxia-activated prodrug, in patients with advanced leukemia.
Article in American journal of hematology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01149915 (A Phase I Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of TH-302, a Hypoxia-Activated Prodrug, in Patients With Advanced Leukemias), which is not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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 Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of TH-302, a Hypoxia-Activated Prodrug, in Patients With Advanced Leukemias
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- Substrate stiffness regulates HIF-1α signalling via β1-integrin/myosin-2/NF-κB axis.Journal of translational medicine · 2026Article
- Stearoyl-CoA desaturase 1 integrates tissue-specific oncogenic pathways into a pan-cancer ferroptosis resistance program.Cell death & disease · 2026Review
- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- Review
- Article
- HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.Genes & diseases · 2024Review
- Predicting response to combination evofosfamide and immunotherapy under hypoxic conditions in murine models of colon cancer.Mathematical biosciences and engineering : MBE · 2023Article
- Bone Marrow Microenvironment as a Source of New Drug Targets for the Treatment of Acute Myeloid Leukaemia.International journal of molecular sciences · 2022Review
- Targeting hypoxia in solid and haematological malignancies.Journal of experimental & clinical cancer research : CR · 2022Review
- Human acute myeloid leukemia stem cells: evolution of concept.Blood research · 2022Review
- A cross-sectional study of chemotherapy-related AKI.European journal of clinical pharmacology · 2021Article
- Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development.Experimental hematology & oncology · 2021Review
- Acute Myeloid Leukemia Mutations and Future Mechanistic Target to Overcome Resistance.Current treatment options in oncology · 2021Review
- Therapeutic Targeting of the Leukaemia Microenvironment.International journal of molecular sciences · 2021Review
- The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities.Frontiers in immunology · 2021Review
- The Hypoxia-Activated Prodrug TH-302: Exploiting Hypoxia in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Establishment of Prognosis Model in Acute Myeloid Leukemia Based on Hypoxia Microenvironment, and Exploration of Hypoxia-Related Mechanisms.Frontiers in genetics · 2021Article
- Location First: Targeting Acute Myeloid Leukemia Within Its Niche.Journal of clinical medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor hypoxia causes resistance to radiation and chemotherapy. Evofosfamide (TH-302) has exhibited specific hypoxia-dependent cytotoxicity against primary acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) samples in vitro. Based on these findings, a Phase I study of evofosfamide was designed for patients with relapsed/refractory leukemia (NCT01149915). In this open-label study, patients were treated with evofosfamide as a 30-60 min/day infusion on Days 1-5 of a 21-day cycle (Arm A, n = 38) or as a continuous infusion over 120 hr over Days 1-5 of a 21-day cycle (Arm B, n = 11). Forty-nine patients were treated including 39 (80%) with AML and 9 (18%) with ALL. Patients had received a median of five prior therapies. In Arm A, the dose-limiting toxicities (DLTs) were grade 3 esophagitis, observed at a dose of 550 mg/m(2) . The maximum tolerated dose (MTD) was a daily dose of 460 mg/m(2) . In Arm B, the DLTs were grade 3 stomatitis and hyperbilirubinemia, observed at a daily dose of 460 mg/m(2) . The continuous infusion MTD was a daily dose of 330 mg/m(2) . Hypoxia markers HIF-1α and CAIX were highly expressed in leukemic bone marrow and were significantly reduced after evofosfamide therapy. The combined overall response rate in Arms A and B was 6% (2 CR/CRi and 1 PR), with all responses seen in Arm A. Evofosfamide has shown limited activity in heavily pretreated leukemia patients. Further evaluation investigating evofosfamide in combination with cytotoxic or demethylating agents is warranted. Am. J. Hematol. 91:800-805, 2016. © 2016 Wiley Periodicals, Inc.
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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.