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Chemotherapy: metronomic

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Synonym(s): Metronomic chemotherapy, Continuous low dose chemotherapy


Metronomic chemotherapy

  • Differs from traditional chemotherapy in that it is given at a low-dose that is administered every 24-48 hours.
    It is very important to recognize that the evidence in support of metronomic chemotherapy in veterinary patients is very limited. However, the evidence produced to date does indicate that extrapolations made from in vitro studies and the treatment of human patients may have some foundation.

Mechanisms of action

  • 1. Inhibits angiogenesis thus decreasing nutritional support of tumor.
  • Induces endothelial cell apoptosis.
  • Inhibits local proliferation of circulating endothelial cells (CEC) and circulating endothelial precursors (CEP) derived from the bone marrow.
  • Modulates levels of cytokines that increase angiogenesis, eg vascular endothelial growth factor (VEGF) and angiogenesis inhibitor, thrombospondin-1 (TSP-1).
  • 2. Immune modulation: suppression of regulatory T-cells (T-regs) that are involved in the development of tolerance to tumor cells.
  • 3. Direct tumor cell growth inhibition by tyrosine kinase inhibitors (TKIs) such as Toceranib Toceranib phosphate and Masitinib Masitinib.
  • 4. Apoptosis induced by NSAIDs Analgesia: NSAID.
  • 5. Possible decreased risk of development of drug resistance due to relative genetic stability of non tumor target cells.

Toxicities

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Drugs

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Reported uses of metronomic chemotherapy in veterinary patients

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Additional comments

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Schrempp D R, Childress M O, Stewart J C et al (2013) Metronomic administration of chlorambucil for treatment of dogs with urinary bladder transitional cell carcinoma. JAVMA 242 (11), 1534-1538 PubMed.
  • Leach T N, Childress M O, Greene S N et al (2012) Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer. Vet Comp Oncol 10 (2), 102-112 PubMed.
  • Burton J H, Mitchell L, Thamm D H et al (2011) Low-dose cyclophosphamide selectively decreases regulatory T cells and inhibits angiogenesis in dogs with soft tissue sarcoma. JVIM 25 (4), 920-926 PubMed.
  • Tripp C D, Fidel J, Anderson C L et al (2011) Tolerability of metronomic administration of lomustine in dogs with cancer. JVIM 25 (2), 278-284 PubMed.
  • Elmslie R E, Glawe P, Dow S W (2008) Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. JVIM 22 (6), 1373-1379 PubMed.
  • Lana S, U'ren L, Plaza S et al (2007) Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs.​ JVIM 21 (4), 764-769 PubMed.

Other sources of information

  • Woods J P, Boston S, Mutsaers A J, Saam D E, Coomber B (2012) Continuous low-dose (metronomic) oral chemotherapy of canine appendicular osteosarcoma. ACVIM Proceedings.

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