Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma

Chawla, Sant P.; Cranmer, Lee D.; Van Tine, Brian A.; Reed, Damon R.; Okuno, Scott H.; Butrynski, James E.; Adkins, Douglas R.; Hendifar, Andrew E.; Kroll, Stew; Ganjoo, Kristen N.

doi:10.1200/jco.2013.54.3660

Cited by 155Sarcoma Diagnosis and TreatmentBioactive Compounds and Antitumor AgentsPARP inhibition in cancer therapy

Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma

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Chawla, Sant P., Cranmer, Lee D., Van Tine, Brian A., Reed, Damon R., Okuno, Scott H., Butrynski, James E., Adkins, Douglas R., Hendifar, Andrew E. +2 more·2014·Journal of Clinical Oncology

DOI 10.1200/jco.2013.54.3660PMC PMC4588714

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Abstract

PURPOSE: TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. PATIENTS AND METHODS: In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. RESULTS: Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity. CONCLUSION: PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088).

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Results from recently published phase II clinical trials for TH-302 in combination with gemcitabine in pancreatic cancer or in combination with doxorubicin in soft tissue sarcoma are encouraging.
“Results from recently published phase II clinical trials for TH-302 in combination with gemcitabine in pancreatic cancer (Borad et al., 2015) or in combination with doxorubicin in soft tissue sarcoma (Chawla et al., 2014) are encouraging, and phase III studies have been initiated.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Chawla et al., 2014

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New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
Exploiting tumour hypoxia in cancer treatment
Brown, J. M., & Wilson, W. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1367 · Cited by 2,828 · see citing works
Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial
Judson, I. R., Verweij, J., Gelderblom, H. A. J., Hartmann, J. T., Schöffski, P., Blay, J., Kerst, J. M., Šufliarský, J., Whelan, J. S., Hohenberger, P., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70063-4 · Cited by 1,185 · see citing works
Detection and Characterization of Tumor Hypoxia Using pO <sub>2</sub> Histography
Vaupel, P., Höckel, M., & Mayer, A. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1628 · Cited by 728 · see citing works
Prognostic Factors for the Outcome of Chemotherapy in Advanced Soft Tissue Sarcoma: An Analysis of 2,185 Patients Treated With Anthracycline-Containing First-Line Regimens—A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study
Van Glabbeke, M., van Oosterom, A. T., Oosterhuis, J. W., Mouridsen, H., Crowther, D., Somers, R., Verweij, J., Santoro, A., Buesa, J., & Tursz, T. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.1.150 · Cited by 608 · see citing works
Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies
Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., & Toomey, D. (2003) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(03)00003-3 · Cited by 559 · see citing works
Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells.
Teicher, B. A., Lazo, J. S., & Sartorelli, A. C. (1981) · PubMed · Cited by 555 · see citing works
The distribution of the anticancer drug Doxorubicin in relation to blood vessels in solid tumors
Primeau, A. J., Rendon, A., Hedley, D., Lilge, L., & Tannock, I. F. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1664 · Cited by 499 · see citing works
Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas
Glabbeke, M. M. V., Verweij, J., Judson, I. R., & Nielsen, O. S. (2002) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00398-7 · Cited by 462 · see citing works
Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer.
Kaanders, J. H. A. M., Wijffels, K. I. E. M., Marres, H. A. M., Ljungkvist, A. S. E., Pop, L. A. M., van den Hoogen, F. J. A., de Wilde, P. C. M., Bussink, J., Raleigh, J. A., & van der Kogel, A. J. (2002) · PubMed · Cited by 357 · see citing works
Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Casali, P. G., & Blay, J. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq209 · Cited by 256 · see citing works
Phase III Trial of Two Investigational Schedules of Ifosfamide Compared With Standard-Dose Doxorubicin in Advanced or Metastatic Soft Tissue Sarcoma: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study
Lorigan, P. C., Verweij, J., Pápai, Z., Rodenhuis, S., Cesne, A. L., Leahy, M. G., Radford, J. A., Glabbeke, M. M. V., Kirkpatrick, A., Hogendoorn, P. C. W., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.09.7717 · Cited by 256 · see citing works
Significant clinical benefit of first‐line palliative chemotherapy in advanced soft‐tissue sarcoma
Karavasilis, V., Seddon, B. M., Ashley, S., Al‐Muderis, O., Fisher, C., & Judson, I. R. (2008) · Cancer · doi:10.1002/cncr.23332 · Cited by 253 · see citing works
[18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression
Rajendran, J. G., Wilson, D. C., Conrad, E. U., Peterson, L. M., Bruckner, J. D., Rasey, J. S., Chin, L. K., Hofstrand, P. D., Grierson, J. R., Eary, J. F., et al. (2003) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-002-1096-7 · Cited by 248 · see citing works
Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas
Sleijfer, S., Ouali, M., Glabbeke, M. M. V., Krarup‐Hansen, A., Rodenhuis, S., Cesne, A. L., Hogendoorn, P. C. W., Verweij, J., & Blay, J. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2009.09.022 · Cited by 243 · see citing works
Hypoxia in human soft tissue sarcomas: Adverse impact on survival and no association with p53 mutations
Nordsmark, M., Alsner, J., Keller, J. O., Nielsen, O. S., Jensen, O. M., Horsman, M. R., & Overgaard, J. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1728 · Cited by 226 · see citing works
Molecular and Cellular Pharmacology of the Hypoxia-Activated Prodrug TH-302
Meng, F., Evans, J., Bhupathi, D., Banica, M., Lan, L., Lorente, G., Duan, J.-X., Cai, X., Mowday, A. M., Guise, C. P., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0634 · Cited by 205 · see citing works
Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential
Francis, P., Namløs, H. M., Müller, C., Edén, P., Fernebro, J., Berner, J., Bjerkehagen, B., Åkerman, M., Bendahl, P., Isinger-Ekstrand, A., et al. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-73 · Cited by 168 · see citing works
Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of TH-302, a Hypoxia-Activated Prodrug, in Patients with Advanced Solid Malignancies
Weiss, G. J., Infante, J. R., Chiorean, E. G., Borad, M. J., Bendell, J. C., Molina, J. R., Tibes, R., Ramanathan, R. K., Lewandowski, K., Jones, S. F., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3425 · Cited by 154 · see citing works
Self-citation
Clinical Pharmacokinetics and Pharmacodynamics of Ifosfamide and its Metabolites
Kerbusch, T., de Kraker, J., Keizer, H. J., van Putten, J. W. G., Groen, H. J. M., Jansen, R. L. H., Schellens, J. H. M., & Beijnen, J. H. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140010-00004 · Cited by 131 · see citing works
Targeting hypoxic tumour cells to overcome metastasis
Bennewith, K. L., & Dedhar, S. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-504 · Cited by 109 · see citing works
Pretreatment oxygenation profiles of human soft tissue sarcomas
Brizel, D. M., Rosner, G. L., Harrelson, J. M., Prosnitz, L. R., & Dewhirst, M. W. (1994) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(92)90950-m · Cited by 104 · see citing works
Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. ESMO/CONTICANET/EUROBONET Consensus Panel of Experts.
Whelan, J. S., Casali, P. G., & Blay, J. (2010) · UCL Discovery (University College London) · Cited by 96 · see citing works
Response of aerobic and hypoxic cells in a solid tumor to adriamycin and cyclophosphamide and interaction of the drugs with radiation.
Tannock, I. F. (1982) · PubMed · Cited by 88 · see citing works
A Phase I Study of the Safety and Pharmacokinetics of the Hypoxia-Activated Prodrug TH-302 in Combination with Doxorubicin in Patients with Advanced Soft Tissue Sarcoma
Ganjoo, K. N., Cranmer, L. D., Butrynski, J. E., Rushing, D. A., Adkins, D., Okuno, S. H., Lorente, G., Kroll, S., Langmuir, V. K., & Chawla, S. P. (2011) · Oncology · doi:10.1159/000327739 · Cited by 81 · see citing works
Self-citation
Histology-driven chemotherapy of soft-tissue sarcoma
Eriksson, M. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq285 · Cited by 55 · see citing works
Systemic therapy for advanced soft tissue sarcomas
Riedel, R. F. (2011) · Cancer · doi:10.1002/cncr.26415 · Cited by 42 · see citing works
Metastatic Soft Tissue Sarcoma in Adults
Nielsen, O. S., Blay, J., Judson, I. R., Glabbeke, M. M. V., Verweij, J., & van Oosterom, A. T. (2003) · American Journal of Cancer · doi:10.2165/00024669-200302030-00005 · Cited by 21 · see citing works
Oxygen dependence of the cytotoxicity of the enediyne anti-tumour antibiotic esperamicin A1.
Batchelder, R. M., Wilson, W. R., Hay, M. P., & Denny, W. A. (1996) · Europe PMC (PubMed Central) · Cited by 16 · see citing works

Flagged first, then by citations

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Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Han, F., Du, Y., Shi, H., & Zhou, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01332-8 · Cited by 1,612 · see citing works
The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment
Emami Nejad, A., Najafgholian, S., Rostami, A., Sistani, A., Shojaeifar, S., Esparvarinha, M., Nedaeinia, R., Haghjooy Javanmard, S., Taherian, M., Ahmadlou, M., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-020-01719-5 · Cited by 693 · see citing works
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Wigerup, C., Påhlman, S., & Bexell, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.009 · Cited by 687 · see citing works
“Results from recently published phase II clinical trials for TH-302 in combination with gemcitabine in pancreatic cancer (Borad et al., 2015) or in combination with doxorubicin in soft tissue sarcoma (Chawla et al., 2014) are encouraging, and phase III studies have been initiated.”
Background
Hypoxia-targeted drug delivery
Sharma, A. K., Arambula, J. F., Koo, S., Kumar, R., Singh, H., Sessler, J. L., & Kim, J. S. (2018) · Chemical Society Reviews · doi:10.1039/c8cs00304a · Cited by 547 · see citing works
Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target
Infantino, V., Santarsiero, A., Convertini, P., Todisco, S., & Iacobazzi, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115703 · Cited by 511 · see citing works
Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499 · see citing works
Theranostic Liposomes with Hypoxia-Activated Prodrug to Effectively Destruct Hypoxic Tumors Post-Photodynamic Therapy
Feng, L., Cheng, L., Dong, Z., Tao, D., Barnhart, T. E., Cai, W., Chen, M., & Liu, Z. (2016) · ACS Nano · doi:10.1021/acsnano.6b07525 · Cited by 425 · see citing works
Recent Advances in Glucose‐Oxidase‐Based Nanocomposites for Tumor Therapy
Wang, M., Wang, D., Chen, Q., Li, C., Li, Z., & Lin, J. (2019) · Small · doi:10.1002/smll.201903895 · Cited by 305 · see citing works
Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial
Tap, W. D., Pápai, Z., Tine, B. A. V., Attia, S., Ganjoo, K. N., Jones, R. L., Schuetze, S. M., Reed, D. R., Chawla, S. P., Riedel, R. F., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30381-9 · Cited by 304 · see citing works
Self-citation
Therapeutic journery of nitrogen mustard as alkylating anticancer agents: Historic to future perspectives
Singh, R. K., Kumar, S., Prasad, D. N., & Bhardwaj, T. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.04.001 · Cited by 284 · see citing works
Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: Opportunities, challenges, and future development
Sun, Y., Zhao, D., Wang, G., Wang, Y., Cao, L., Sun, J., Jiang, Q., & He, Z. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.01.004 · Cited by 250 · see citing works
Reprogramming of the Tumor in the Hypoxic Niche: The Emerging Concept and Associated Therapeutic Strategies
Qiu, G., Jin, M., Dai, J., Sun, W., Feng, J., & Jin, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.05.002 · Cited by 245 · see citing works
Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs
Phillips, R. M. (2016) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-015-2920-7 · Cited by 240 · see citing works
In Vivo Bioorthogonal Chemistry Enables Local Hydrogel and Systemic Pro-Drug To Treat Soft Tissue Sarcoma
Oneto, J. M. M., Khan, I. A., Seebald, L. M., & Royzen, M. (2016) · ACS Central Science · doi:10.1021/acscentsci.6b00150 · Cited by 216 · see citing works
Improving Cancer Immunotherapy by Targeting the Hypoxic Tumor Microenvironment: New Opportunities and Challenges
Noman, M. Z., Hasmim, M., Lequeux, A., Xiao, M., Duhem, C., Chouaı̈b, S., Berchem, G., & Janji, B. (2019) · Cells · doi:10.3390/cells8091083 · Cited by 215 · see citing works
Interfering with Tumor Hypoxia for Radiotherapy Optimization
Telarović, I., Wenger, R. H., & Pruschy, M. N. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02000-x · Cited by 196 · see citing works
Metabolic and hypoxic adaptation to anti‐angiogenic therapy: a target for induced essentiality
McIntyre, A., & Harris, A. L. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404271 · Cited by 185 · see citing works
Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy
Li, Y., Zhao, L., & Li, X.-F. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.700407 · Cited by 167 · see citing works
Hypoxia: a Double-Edged Sword in Cancer Therapy
Manoochehri Khoshinani, H., Afshar, S., & Najafi, R. (2016) · Cancer Investigation · doi:10.1080/07357907.2016.1245317 · Cited by 147 · see citing works
Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy
Mistry, I. N., Thomas, M., Calder, E. D. D., Conway, S. J., & Hammond, E. M. (2017) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2017.03.024 · Cited by 143 · see citing works
Stepwise Degradable Nanocarriers Enabled Cascade Delivery for Synergistic Cancer Therapy
Yang, Y., Lu, Y., Abbaraju, P. L., Azimi, I., Lei, C., Tang, J., Jambhrunkar, M., Fu, J., Zhang, M., Liu, Y., et al. (2018) · Advanced Functional Materials · doi:10.1002/adfm.201800706 · Cited by 120 · see citing works
TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [18F]HX4 Hypoxia PET Imaging
Peeters, S. G. J. A., Zegers, C. M. L., Biemans, R., Lieuwes, N. G., van Stiphout, R. G. P. M., Yaromina, A., Sun, J. D., Hart, C. P., Windhorst, A. D., van Elmpt, W., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0018 · Cited by 112 · see citing works
Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials
Spiegelberg, L., Houben, R. M. A., Niemans, R., Ruysscher, D. D., Yaromina, A., Theys, J., Guise, C. P., Smaill, J. B., Patterson, A. V., Lambin, P., et al. (2019) · Clinical and Translational Radiation Oncology · doi:10.1016/j.ctro.2019.01.005 · Cited by 113 · see citing works
Natural Killer Cell Interactions With Myeloid Derived Suppressor Cells in the Tumor Microenvironment and Implications for Cancer Immunotherapy
Zalfa, C., & Paust, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.633205 · Cited by 95 · see citing works
Drug radiotherapy combinations: Review of previous failures and reasons for future optimism
Higgins, G. S., O'Cathail, S. M., Muschel, R. J., & McKenna, W. G. (2015) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.12.012 · Cited by 95 · see citing works
Patient‑derived xenograft mouse models: A high fidelity tool for individualized medicine (Review)
Xu, C., Li, X., Liu, P., Li, M., & Luo, F. (2018) · Oncology Letters · doi:10.3892/ol.2018.9583 · Cited by 84 · see citing works
Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments
Feldman, L. A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1384249 · Cited by 90 · see citing works
ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions
Chen, Y.-S., Tian, H., Rong, D., Wang, L., Chen, S., Zeng, J., Xu, H., Mei, J., Wang, L.-Y., Liou, Y., et al. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00338-8 · Cited by 87 · see citing works
Identification of P450 Oxidoreductase as a Major Determinant of Sensitivity to Hypoxia-Activated Prodrugs
Hunter, F. W., Young, R. J., Shalev, Z., Vellanki, R. N., Wang, J., Gu, Y., Joshi, N., Sreebhavan, S., Weinreb, I., Goldstein, D. P., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1107 · Cited by 82 · see citing works
Systemic treatment in adult uterine sarcomas
Desar, I. M. E., Ottevanger, P. B., Benson, C., & van der Graaf, W. T. A. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.12.009 · Cited by 80 · see citing works
Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development
Yao, Y., Li, F., Huang, J., Jin, J., & Wang, H. (2021) · Experimental Hematology and Oncology · doi:10.1186/s40164-021-00233-2 · Cited by 86 · see citing works
Recent advances in dual- and multi-responsive nanomedicines for precision cancer therapy
Zhang, Y., Li, J., & Pu, K. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121906 · Cited by 76 · see citing works
Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models
Benito, J., Ramirez, M. S., Zacharias, N. M., Vélez, J., Harutyunyan, K. G., Lu, H., Shi, Y.-X., Matre, P. R., Jacamo, R. O., Ma, H., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3378 · Cited by 75 · see citing works
Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment
Arroyo‐Crespo, J. J., Armiñán, A., Charbonnier, D., Balzano‐Nogueira, L., Huertas, F., Martí, C., Tarazona, S., Forteza, J., Conesa, A., & Vicent, M. J. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.09.023 · Cited by 73 · see citing works
The Hypoxia-Activated Prodrug TH-302: Exploiting Hypoxia in Cancer Therapy
Li, Y., Zhao, L., & Li, X.-F. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.636892 · Cited by 71 · see citing works
Recent Advances of Organ-on-a-Chip in Cancer Modeling Research
Liu, X., Su, Q., Zhang, X., Yang, W., Ning, J., Jia, K., Xin, J., Li, H., Yu, L., Liao, Y., et al. (2022) · Biosensors · doi:10.3390/bios12111045 · Cited by 68 · see citing works
Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors
Ham, S. L., Joshi, R., Luker, G. D., & Tavana, H. (2016) · Advanced Healthcare Materials · doi:10.1002/adhm.201600644 · Cited by 64 · see citing works
New ways to image and target tumour hypoxia and its molecular responses
Dubois, L. J., Niemans, R., van Kuijk, S. J. A., Panth, K. M., Parvathaneni, N.-K., Peeters, S. G. J. A., Zegers, C. M. L., Rekers, N. H., van Gisbergen, M. W., Biemans, R., et al. (2015) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2015.08.022 · Cited by 56 · see citing works
Targeting Tumor Hypoxia With Hypoxia-Activated Prodrugs
Yeh, J. J., & Kim, W. Y. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.60.0759 · Cited by 54 · see citing works
The application of prodrug-based nano-drug delivery strategy in cancer combination therapy
Ge, Y., Ma, Y., & Li, L. (2016) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2016.06.051 · Cited by 54 · see citing works
Hypoxia Marker GLUT-1 (Glucose Transporter 1) is an Independent Prognostic Factor for Survival in Bladder Cancer Patients Treated with Radical Cystectomy
Boström, P. J., Thoms, J., Sykes, J. R., Ahmed, O., Evans, A., van Rhijn, B. W. G., Mirtti, T. K., Stakhovskyi, O. E., Laato, M. K., Margel, D., et al. (2016) · Bladder Cancer · doi:10.3233/blc-150033 · Cited by 54 · see citing works
Hypoxia Responsive Drug Delivery Systems in Tumor Therapy
Alimoradi, H., Matikonda, S. S., Gamble, A. B., Giles, G. I., & Greish, K. F. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160217130049 · Cited by 53 · see citing works
High Resolution Ultrasound and Photoacoustic Imaging of Orthotopic Lung Cancer in Mice: New Perspectives for Onco-Pharmacology
Raes, F., Sobilo, J., Mée, M. L., Retif, S., Natkunarajah, S., Lerondel, S., & Pape, A. L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153532 · Cited by 52 · see citing works
Development and characterization of a human three-dimensional chondrosarcoma culture for in vitro drug testing
Voissiere, A., Jouberton, E., Maubert, E., Degoul, F., Peyrode, C., Chezal, J.-M., & Miot-Noirault, É. (2017) · PLOS ONE · doi:10.1371/journal.pone.0181340 · Cited by 49 · see citing works
Synthesis and biological evaluation of benzocyclooctene-based and indene-based anticancer agents that function as inhibitors of tubulin polymerization
Herdman, C. A., Strecker, T. E., Tanpure, R. P., Chen, Z., Winters, A., Gerberich, J., Liu, L., Hamel, E., Mason, R. P., Chaplin, D. J., et al. (2016) · MedChemComm · doi:10.1039/c6md00459h · Cited by 49 · see citing works
Hypoxia and its therapeutic possibilities in paediatric cancers
Bernauer, C., Man, Y. K. S., Chisholm, J., Lepicard, E. Y., Robinson, S. P., & SHIPLEY, J. M. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-01107-w · Cited by 48 · see citing works
Significance of Specific Oxidoreductases in the Design of Hypoxia-Activated Prodrugs and Fluorescent Turn off–on Probes for Hypoxia Imaging
Janczy-Cempa, E., Mazuryk, O., Kania, A., & Brindell, M. (2022) · Cancers · doi:10.3390/cancers14112686 · Cited by 45 · see citing works
New Strategies in Sarcoma: Linking Genomic and Immunotherapy Approaches to Molecular Subtype
Lim, J. L., Poulin, N., & Nielsen, T. O. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0831 · Cited by 45 · see citing works
Phase I study of evofosfamide, an investigational hypoxia‐activated prodrug, in patients with advanced leukemia
Badar, T., Handisides, D. R., Benito, J. M., Richie, M. A., Borthakur, G. M., Jabbour, E. J., Harutyunyan, K. G., Konoplev, S. N., Faderl, S. H., Kroll, S., et al. (2016) · American Journal of Hematology · doi:10.1002/ajh.24415 · Cited by 44 · see citing works
Self-citation
A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without Bortezomib in Subjects with Relapsed/Refractory Multiple Myeloma
Laubach, J. P., Liu, C., Raje, N. S., Yee, A. J., Armand, P. A., Schlossman, R. L., Rosenblatt, J. M., Hedlund, J. A., Martin, M. G., Reynolds, C. H., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1325 · Cited by 43 · see citing works
Self-citation
Spotlight on aldoxorubicin (INNO-206) and its potential in the treatment of soft tissue sarcomas: evidence to date
Cranmer, L. D. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s145539 · Cited by 41 · see citing works
Self-citation
Targeting hypoxia and hypoxia‐inducible factor‐1 in the tumor microenvironment for optimal cancer immunotherapy
Kheshtchin, N., & Hadjati, J. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30643 · Cited by 41 · see citing works
Combined Antitumor Therapy with Metronomic Topotecan and Hypoxia-Activated Prodrug, Evofosfamide, in Neuroblastoma and Rhabdomyosarcoma Preclinical Models
Zhang, L., Marrano, P. M., Wu, B. H., Kumar, S., Thorner, P. S., & Baruchel, S. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1853 · Cited by 38 · see citing works
Three dimensional engineered models to study hypoxia biology in breast cancer
Aggarwal, V., Miranda, O., Johnston, P. A., & Sant, S. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.05.030 · Cited by 40 · see citing works
Patient-Derived Xenograft and Organoid Models for Precision Medicine Targeting of the Tumour Microenvironment in Head and Neck Cancer
Lee, T. W., Lai, A., Harms, J. K., Singleton, D. C., Dickson, B. D., Macann, A., Hay, M. P., & Jamieson, S. M. F. (2020) · Cancers · doi:10.3390/cancers12123743 · Cited by 37 · see citing works
Histology-Driven Therapy
Noujaim, J. C., Thway, K., Sheri, A., Keller, C., & Jones, R. L. (2015) · International Journal of Surgical Pathology · doi:10.1177/1066896915606971 · Cited by 37 · see citing works
Radiotherapy Synergizes with the Hypoxia-Activated Prodrug Evofosfamide: In Vitro and In Vivo Studies
Takakusagi, Y., Kishimoto, S., Naz, S., Matsumoto, S., Saito, K., Hart, C. P., Mitchell, J. B., & Krishna, M. C. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7106 · Cited by 35 · see citing works
Overcoming Radioresistance: Small Molecule Radiosensitisers and Hypoxia-activated Prodrugs
Jackson, R. K., Liew, L. P., & Hay, M. P. (2019) · Clinical Oncology · doi:10.1016/j.clon.2019.02.004 · Cited by 35 · see citing works
Construction of a nanotheranostic system Zr-MOF@PPa/AF@PEG for improved photodynamic therapy effects based on the PDT‑oxygen consumption and hypoxia sensitive chemotherapeutic drug
Wang, X., Wang, Z., Ma, W., Wu, X., Fang, W., Guo, C., & Jin, Y. (2021) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2021.112274 · Cited by 35 · see citing works
Efficacy of the hypoxia‐activated prodrug evofosfamide (TH‐302) in nasopharyngeal carcinoma in vitro and in vivo
Huang, Y., Tian, Y., Zhao, Y., Xue, C., Zhan, J., Liu, L., He, X., & Zhang, L. (2018) · 癌症：英文版 · doi:10.1186/s40880-018-0285-0 · Cited by 33 · see citing works
Overview of Current Treatment Options and Investigational Targeted Therapies for Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Zibelman, M. R., & Mehra, R. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000283 · Cited by 32 · see citing works
Hypoxic Jumbo Spheroids On-A-Chip (HOnAChip): Insights into Treatment Efficacy
Refet-Mollof, E., Najyb, O., Chermat, R., Glory, A., Lafontaine, J., Wong, P., & Gervais, T. (2021) · Cancers · doi:10.3390/cancers13164046 · Cited by 32 · see citing works
Anticancer efficacy of the hypoxia‐activated prodrug evofosfamide (TH‐302) in osteolytic breast cancer murine models
Liapis, V., Zinonos, I., Labrinidis, A., Hay, S. J., Ponomarev, V., Panagopoulos, V., Zysk, A., DeNichilo, M. O., Ingman, W. V., Atkins, G. J., et al. (2016) · Cancer Medicine · doi:10.1002/cam4.599 · Cited by 31 · see citing works
Cellular pharmacology of evofosfamide (TH-302): A critical re-evaluation of its bystander effects
Hong, C. R., Dickson, B. D., Jaiswal, J. K., Pruijn, F. B., Hunter, F. W., Hay, M. P., Hicks, K. O., & Wilson, W. R. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.08.027 · Cited by 30 · see citing works
Preclinical Benefit of Hypoxia-Activated Intra-arterial Therapy with Evofosfamide in Liver Cancer
Durán, R., Mirpour, S., Pekurovsky, V., Ganapathy‐Kanniappan, S., Brayton, C. F., Cornish, T. C., Gorodetski, B., Reyes, J., Chapiro, J., Schernthaner, R. E., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0725 · Cited by 29 · see citing works
A phase 1 ‘window-of-opportunity’ trial testing evofosfamide (TH-302), a tumour-selective hypoxia-activated cytotoxic prodrug, with preoperative chemoradiotherapy in oesophageal adenocarcinoma patients
Larue, R. T. H. M., Voorde, L. V. D., Berbée, M., van Elmpt, W., Dubois, L. J., Panth, K. M., Peeters, S. G. J. A., Claessens, A., Schreurs, W. M. J., Nap, M., et al. (2016) · BMC Cancer · doi:10.1186/s12885-016-2709-z · Cited by 29 · see citing works
Tumor Hypoxia As an Enhancer of Inflammation-Mediated Metastasis: Emerging Therapeutic Strategies
DiGiacomo, J. W., & Gilkes, D. M. (2018) · Targeted Oncology · doi:10.1007/s11523-018-0555-4 · Cited by 29 · see citing works
Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas
Yoon, C., Lee, H.-J., Park, D. J., Lee, Y., Tap, W. D., Eisinger‐Mathason, T. S. K., Hart, C. P., Choy, E., Simon, M. C., & Yoon, S. S. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.186 · Cited by 28 · see citing works
An Intratumor Pharmacokinetic/Pharmacodynamic Model for the Hypoxia-Activated Prodrug Evofosfamide (TH-302): Monotherapy Activity is Not Dependent on a Bystander Effect
Hong, C. R., Wilson, W. R., & Hicks, K. O. (2018) · Neoplasia · doi:10.1016/j.neo.2018.11.009 · Cited by 28 · see citing works
Hypoxia Imaging As a Guide for Hypoxia-Modulated and Hypoxia-Activated Therapy
Brender, J., Saida, Y., Devasahayam, N., Krishna, M. C., & Kishimoto, S. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0176 · Cited by 28 · see citing works
Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models
Sun, J. D., Liu, Q., Ahluwalia, D., Ferraro, D. J., Wang, Y., Jung, D. T., Matteucci, M. D., & Hart, C. P. (2016) · Cancer Biology & Therapy · doi:10.1080/15384047.2016.1139268 · Cited by 27 · see citing works
Emerging targets for radioprotection and radiosensitization in radiotherapy
Kumar, S., Singh, R. K., & Meena, R. (2016) · Tumor Biology · doi:10.1007/s13277-016-5117-8 · Cited by 28 · see citing works
Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors
Schneider, M. A., Linecker, M., Fritsch, R., Muehlematter, U. J., Stocker, D., Pestalozzi, B. C., Samaras, P., Jetter, A., Kron, P., Petrowsky, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24069-w · Cited by 26 · see citing works
Combination treatment with hypoxia-activated prodrug evofosfamide (TH-302) and mTOR inhibitors results in enhanced antitumor efficacy in preclinical renal cell carcinoma models.
Sun, J. D., Ahluwalia, D., Liu, Q., Li, W., Wang, Y., Meng, F., Bhupathi, D., Matteucci, M. D., & Hart, C. P. (2015) · Europe PMC (PubMed Central) · Cited by 26 · see citing works
Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1 inhibition
Meng, F., Bhupathi, D., Sun, J. D., Liu, Q., Ahluwalia, D., Wang, Y., Matteucci, M. D., & Hart, C. P. (2015) · BMC Cancer · doi:10.1186/s12885-015-1387-6 · Cited by 25 · see citing works
Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends
Ki, M., Kim, D. H., Abdelhamid, M. A. A., & Pack, S. P. (2025) · Biosensors · doi:10.3390/bios15110737 · Cited by 29 · see citing works
Hypoxia Imaging with PET Correlates with Antitumor Activity of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) in Rodent Glioma Models
Stokes, A. M., Hart, C. P., & Quarles, C. C. (2016) · Tomography · doi:10.18383/j.tom.2016.00259 · Cited by 24 · see citing works
Hypoxia-activated prodrug: an appealing preclinical concept yet lost in clinical translation
Lindner, L. H. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30401-1 · Cited by 24 · see citing works
Switch maintenance therapy with anlotinib after chemotherapy in unresectable or metastatic soft tissue sarcoma: a single-center retrospective study
Liu, J., Deng, Y., & Jiang, Y. (2020) · Investigational New Drugs · doi:10.1007/s10637-020-01015-z · Cited by 23 · see citing works
Impact of Tumour Hypoxia on Evofosfamide Sensitivity in Head and Neck Squamous Cell Carcinoma Patient-Derived Xenograft Models
Harms, J. K., Lee, T. W., Wang, T., Lai, A., Kee, D., Chaplin, J. M., McIvor, N., Hunter, F. W., Macann, A., Wilson, W. R., et al. (2019) · Cells · doi:10.3390/cells8070717 · Cited by 21 · see citing works
Salvage Treatment of Adrenocortical Carcinoma with Trofosfamide
on behalf of the German Adrenocortical Carcinoma Study Group, Kroiß, M., Deutschbein, T., Schlötelburg, W., Ronchi, C. L., Neu, B., Müller, H., Quinkler, M. O., Hahner, S., Heidemeier, A., et al. (2016) · Hormones and Cancer · doi:10.1007/s12672-016-0260-7 · Cited by 22 · see citing works
Phase III Soft Tissue Sarcoma Trials: Success or Failure?
Lee, A. T. J., Pollack, S. M., Huang, P. H., & Jones, R. L. (2017) · Current Treatment Options in Oncology · doi:10.1007/s11864-017-0457-1 · Cited by 22 · see citing works
Hypoxia theranostics of a human prostate cancer xenograft and the resulting effects on the tumor microenvironment
Krishnamachary, B., Mironchik, Y., Jacob, D., Goggins, E. S., Kakkad, S. M., Ofori, F., Doré-Savard, L., Bharti, S. K., Wildes, F. B., Penet, M., et al. (2020) · Neoplasia · doi:10.1016/j.neo.2020.10.001 · Cited by 22 · see citing works
Deep-learning and MR images to target hypoxic habitats with evofosfamide in preclinical models of sarcoma
Jardim‐Perassi, B. V., Mu, W., Huang, S., Tomaszewski, M. R., Poleszczuk, J., Abdalah, M. A., Budzevich, M. M., Dominguez‐Viqueira, W., Reed, D. R., Bui, M. M., et al. (2021) · Theranostics · doi:10.7150/thno.56595 · Cited by 23 · see citing works
Self-citation
Banoxantrone Coordinated Metal−Organic Framework for Photoacoustic Imaging‐Guided High Intensity Focused Ultrasound Therapy
Sun, T., Li, J., Zeng, C., Luo, C., Luo, X., Zhang, H., & Li, H. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202202348 · Cited by 21 · see citing works
Multimodal targeting of tumor vasculature and cancer stem-like cells in sarcomas with VEGF-A inhibition, HIF-1α inhibition, and hypoxia-activated chemotherapy
Yoon, C., Chang, K. K., Lee, J. H., Tap, W. D., Hart, C. P., Simon, M. C., & Yoon, S. S. (2016) · Oncotarget · doi:10.18632/oncotarget.10212 · Cited by 21 · see citing works
Retracted
Functional CRISPR and shRNA Screens Identify Involvement of Mitochondrial Electron Transport in the Activation of Evofosfamide
Hunter, F. W., Devaux, J. B. L., Meng, F., Hong, C. R., Khan, A., Tsai, P., Ketela, T. W., Sharma, I., Kakadia, P. M., Marastoni, S., et al. (2019) · Molecular Pharmacology · doi:10.1124/mol.118.115196 · Cited by 18 · see citing works
Investigational Hypoxia-Activated Prodrugs: Making Sense of Future Development
Su, M., Zhang, L., Huang, Z., Shi, J.-J., & Lu, J. (2018) · Current Drug Targets · doi:10.2174/1389450120666181123122406 · Cited by 18 · see citing works
Hypoxia-Targeting Drug Evofosfamide (TH-302) Enhances Sunitinib Activity in Neuroblastoma Xenograft Models
Kumar, S., Sun, J. D., Zhang, L., Mokhtari, R. B., Wu, B. H., Meng, F., Liu, Q., Bhupathi, D., Wang, Y., Yeger, H., et al. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.05.004 · Cited by 17 · see citing works
Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall
Nyström, H., Jönsson, M., Hartman, L. W., Nilbert, M. C., & Carneiro, A. (2017) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2016-204149 · Cited by 17 · see citing works
Phase I and phase II clinical trials in sarcoma: Implications for drug discovery and development
Lee, D. Y., Staddon, A. P., Shabason, J. E., & Sebro, R. (2019) · Cancer Medicine · doi:10.1002/cam4.1958 · Cited by 17 · see citing works
Targeting tumor microenvironmental barriers to enhance immunogenic cell death in solid tumors
Zhang, J., Han, W., Zhang, M., Yi, Y., & Long, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1672601 · Cited by 16 · see citing works
The fate of new fosfamides in phase III studies in advanced soft tissue sarcoma
Constantinidou, A., & van der Graaf, W. T. A. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.07.043 · Cited by 16 · see citing works
Therapeutic Strategies to Block the Hypoxic Response
DiGiacomo, J. W., & Gilkes, D. M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-12734-3_10 · Cited by 16 · see citing works
Clinical Limitations of Photon, Proton and Carbon Ion Therapy for Pancreatic Cancer
Dell’Oro, M., Short, M., Wilson, P., & Bezak, E. (2020) · Cancers · doi:10.3390/cancers12010163 · Cited by 15 · see citing works
Exploiting tumor hypoxia for cancer treatment
Niemans (2018) · doi:10.26481/dis.20180626rn · Cited by 14 · see citing works
Anticancer efficacy of the hypoxia‐activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma
Liapis, V., Zysk, A., DeNichilo, M. O., Zinonos, I., Hay, S. J., Panagopoulos, V., Shoubridge, A. J., Difelice, C., Ponomarev, V., Ingman, W. V., et al. (2017) · Cancer Medicine · doi:10.1002/cam4.1115 · Cited by 13 · see citing works
Efficacy thresholds for clinical trials with advanced or metastatic leiomyosarcoma patients: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group meta-analysis based on a literature review for soft-tissue sarcomas
Kantidakis, G., Litière, S., Neven, A., Vinches, M., Judson, I. R., Schöffski, P., Wardelmann, E., Stacchiotti, S., D’Ambrosio, L., Marreaud, S. I., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.06.025 · Cited by 13 · see citing works
CCI-779 (Temsirolimus) exhibits increased anti-tumor activity in low EGFR expressing HNSCC cell lines and is effective in cells with acquired resistance to cisplatin or cetuximab
Niehr, F., Weichert, W., Stenzinger, A., Budach, V., & Tinhofer, I. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0456-6 · Cited by 12 · see citing works
AI-Radiomics Can Improve Inclusion Criteria and Clinical Trial Performance
Tomaszewski, M. R., Fan, S., García, A. L., Qi, J., Kim, Y., Gatenby, R. A., Schabath, M. B., Tap, W. D., Reinke, D. K., Makanji, R. J., et al. (2022) · Tomography · doi:10.3390/tomography8010028 · Cited by 12 · see citing works
Self-citation

A phase II dose expansion of TH-302 in combination with doxorubicin in soft-tissue sarcoma.
Cranmer, L. D., Ganjoo, K. N., Adkins, D. R., Reed, D. R., Okuno, S. H., Butrynski, J. E., Rushing, D. A., Lorente, G., Kroll, S., & Chawla, S. P. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.10024 · Cited by 2 · see citing works
Self-citation
Phase I/II study of TH-302 combined with doxorubicin in soft tissue sarcoma.
Cranmer, L. D., Chawla, S. P., Rushing, D. A., Butrynski, J. E., Okuno, S. H., Adkins, D. R., Langmuir, V. K., Lorente, G., Kroll, S., & Ganjoo, K. N. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.10036 · Cited by 4 · see citing works
Self-citation
A Phase I Study of the Safety and Pharmacokinetics of the Hypoxia-Activated Prodrug TH-302 in Combination with Doxorubicin in Patients with Advanced Soft Tissue Sarcoma
Ganjoo, K. N., Cranmer, L. D., Butrynski, J. E., Rushing, D. A., Adkins, D., Okuno, S. H., Lorente, G., Kroll, S., Langmuir, V. K., & Chawla, S. P. (2011) · Oncology · doi:10.1159/000327739 · Cited by 81 · see citing works
Self-citation
Randomized phase III, multicenter, open-label study comparing TH-302 in combination with doxorubicin versus doxorubicin alone in subjects with locally advanced unresectable or metastatic soft tissue sarcoma.
Chawla, S. P., Reinke, D. K., Saks, S., Kroll, S., & Tap, W. D. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.30.15_suppl.tps10100 · Cited by 2 · see citing works
Self-citation
Hypoxia-activated TH-302 for advanced soft-tissue sarcoma
Rahman, A. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70447-4

Authors: Chawla, S. P., Cranmer, L. D., Van Tine, B. A., Reed, D. R., Okuno, S. H., Butrynski, J. E., Adkins, D. R., Hendifar, A. E., Kroll, S., & Ganjoo, K. N.
Affiliations: Cedars-Sinai Medical Center (US)
Sant P. Chawla, Sarcoma Oncology Center, Santa Monica; Andrew E. Hendifar, Cedars Sinai Medical Center, Los Angeles; Stew Kroll, Threshold Pharmaceuticals, South San Francisco; Kristen N. Ganjoo, Stanford University Medical Center, Stanford, CA; Lee D. Cranmer, University of Arizona Cancer Center, Tucson, AZ; Brian A. Van Tine and Douglas R. Adkins, Washington University in St Louis, St Louis, MO; Damon R. Reed, Moffitt Cancer Center and Research Institute, Tampa, FL; Scott H. Okuno, Mayo Clinic,...
ORCID: Chawla, Sant P.
Cranmer, Lee D.
Reed, Damon R.
Okuno, Scott H.
Adkins, Douglas R.
Hendifar, Andrew E.
Ganjoo, Kristen N.
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2014-10-10
Volume: 32
Issue: 29
Pages: 3299-3306
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2013.54.3660
PMC: PMC4588714
OpenAlex: W2162527266
Cited by: 155
References: 29
Citations by year: 2026: 3 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 11 · 2021: 20 · 2020: 10 · 2019: 12 · 2018: 14 · 2017: 17 · 2016: 33 · 2015: 19
FWCI: 18.46
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Oncology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Amgen
GlaxoSmithKline
Merck KGaA
EMD Serono
National Cancer Institute (P30CA076292)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords: TH-302, doxorubicin, soft tissue sarcoma, hypoxia-activated prodrug, combination chemotherapy, maintenance monotherapy, progression-free survival, anticancer activity, drug safety and tolerability, first-line therapy
MeSH terms: Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Doxorubicin, Female, Humans, Male, Middle Aged, Nitroimidazoles, Phosphoramide Mustards, Prodrugs, Sarcoma, Survival Rate, Treatment Outcome

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Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma

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