ArticleCancer chemotherapy and pharmacology2012
TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.
Article in Cancer chemotherapy and pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 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.
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Who cites it
64 citing papers in PubMed, 114 citations in OpenAlex.
- A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without Bortezomib in Subjects with Relapsed/Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma.JCI insight · 2018Trial
- Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models.Cancer biology & therapy · 2016Trial
- Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer.Cancer biology & therapy · 2015Trial
- Deficiencies in the Fanconi anemia or homologous recombination pathway enhance the antitumor effects of the hypoxia-activated prodrug CP-506.Molecular therapy. Oncology · 2026Article
- PISTOL MRI allows noninvasive assessment of changes in tumor oxygenation post hypoxia targeted therapy.Scientific reports · 2025Article
- Article
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.The Journal of experimental medicine · 2025Article
- Hypoxia as a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Evofosfamide and Gemcitabine Act Synergistically in Pancreatic Cancer Xenografts by Dual Action on Tumor Vasculature and Inhibition of Homologous Recombination DNA Repair.Antioxidants & redox signaling · 2023Article
- Smart nanoparticles and microbeads for interventional embolization therapy of liver cancer: state of the art.Journal of nanobiotechnology · 2023Review
- Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug evaluation.Frontiers in pharmacology · 2022Article
- Hypoxia-Activated Prodrug Evofosfamide Treatment in Pancreatic Ductal Adenocarcinoma Xenografts Alters the Tumor Redox Status to Potentiate Radiotherapy.Antioxidants & redox signaling · 2021Article
- Interfering with Tumor Hypoxia for Radiotherapy Optimization.Journal of experimental & clinical cancer research : CR · 2021Review
- Perspectives on Hypoxia Signaling in Tumor Stroma.Cancers · 2021Review
- The roles of PD-1/PD-L1 in the prognosis and immunotherapy of prostate cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Review
- Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
purposeSubregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models.
methodsSeven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer.
resultsThe antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity.
conclusionsTH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.
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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.