ArticleNeoplasia (New York, N.Y.)2014
Intermittent metronomic drug schedule is essential for activating antitumor innate immunity and tumor xenograft regression.
Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Trial
- Article
- Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.MedComm · 2025Review
- Effects of the Alkylating Agent Cyclophosphamide in Potentiating Anti-Tumor Immunity.International journal of molecular sciences · 2025Review
- Synergistic effects of herpes oncolytic virus and cyclophosphamide for recurrent malignant glioma: a narrative review.Annals of medicine and surgery (2012) · 2024Review
- Mitigating non-genetic resistance to checkpoint inhibition based on multiple states of immune exhaustion.NPJ systems biology and applications · 2024Article
- Metronomic Chemotherapy: Anti-Tumor Pathways and Combination with Immune Checkpoint Inhibitors.Cancers · 2023Review
- Immunogenic chemotherapy: great potential for improving response rates.Frontiers in oncology · 2023Review
- Metronomic Chemotherapy in Pediatric Oncology: From Preclinical Evidence to Clinical Studies.Journal of clinical medicine · 2022Review
- Type-I interferon signaling is essential for robust metronomic chemo-immunogenic tumor regression in murine breast cancer.Cancer research communications · 2022Article
- T Cells Promote Metastasis by Regulating Extracellular Matrix Remodeling following Chemotherapy.Cancer research · 2022Article
- Host response to immune checkpoint inhibitors contributes to tumor aggressiveness.Journal for immunotherapy of cancer · 2021Article
- The Dichotomous Role of Bone Marrow Derived Cells in the Chemotherapy-Treated Tumor Microenvironment.Journal of clinical medicine · 2020Review
- Optimizing adaptive cancer therapy: dynamic programming and evolutionary game theory.Proceedings. Biological sciences · 2020Article
- Diffuse optical spectroscopic imaging reveals distinct early breast tumor hemodynamic responses to metronomic and maximum tolerated dose regimens.Breast cancer research : BCR · 2020Article
- Medium dose intermittent cyclophosphamide induces immunogenic cell death and cancer cell autonomous type I interferon production in glioma models.Cancer letters · 2020Article
- Immunostimulatory and anti-tumor metronomic cyclophosphamide regimens assessed in primary orthotopic and metastatic murine breast cancer.NPJ breast cancer · 2020Article
- Gut Microbiota Profiling in Patients With HER2-Negative Metastatic Breast Cancer Receiving Metronomic Chemotherapy of Capecitabine Compared to Those Under Conventional Dosage.Frontiers in oncology · 2020Article
- Delicate Balances in Cancer Chemotherapy: Modeling Immune Recruitment and Emergence of Systemic Drug Resistance.Frontiers in immunology · 2020Article
- The pro-tumorigenic host response to cancer therapies.Nature reviews. Cancer · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Metronomic chemotherapy using cyclophosphamide (CPA) is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25%) reduction in CPA dose. Moreover, an ∼20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.
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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.