Influence Of Metronomic Chemotherapy In Cancer Treatment

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The use of conventional cytotoxic drugs to cease or slow down the blood vessel growth is called metronomic chemotherapy. It generally refers to low dosage of chemotherapy drugs to eliminate toxicity and also target the tumor cells by anti-angiogenesis.

What is Metronomic Chemotherapy?

Metronomic chemotherapy is a method of treatment which is intended to cure and prevent tumor formation. It is focused towards tumor angiogenesis (formation of new blood vessels) by more frequent and lower-dosage drug administration, in comparison with other conventional chemotherapies.

The probable prevention of tumor formation by metronomic chemotherapy was discovered by experimentation on animal models, and the efficacy of the metronomic approach has been confirmed in clinics.

How does Metronomic Chemotherapy work?

Patients undergoing conventional chemotherapy wait for weeks between treatments. It helps the healthy cells recover. Metronomic chemotherapy is based on the use of chemotherapy drugs in a new way. Unlike the conventional method, in which patients receive large doses of chemotherapy drugs, patients undergoing metronomic chemotherapy receive a small dose of the drug that is one-tenth the normal dose. This small dose is less damaging to healthy cells in the body, and that’s why chemotherapy can be administered more frequently.

It can retard tumor blood vessel growth, by destroying endothelial cells. Endothelial cells form the lining of the newly formed blood vessels, particularly those whose production is fueled by tumors to support their growth. These are the targets of this type of therapy.

Advantages of Metronomic Chemotherapy with different types of Cancer:

In metronomic chemotherapy, drugs are administered long-term, in low doses, and frequently. It has been shown to have a considerable stabilizing effect on cancer and a positive impact on the quality of life of patients, including those with prostate cancer. Also, this therapy can be combined with anti-angiogenic drugs, as well as with other types of therapies that target specific signal-transduction molecules, and with anti-tumor vaccines.

What is the effect of Metronomic Chemotherapy on metastasis?

Metronomic long-term, low-dose chemotherapy has been uncommon in adult oncological practice. Recent studies tested an oral metronomic chemotherapy regimen in a non-randomized clinical trial for the treatment of metastatic breast cancer patients, and this well-tolerated protocol was proven to be efficient.

Does Metronomic Chemotherapy enhance the effect of Chemotherapy?

Studies are in progress to determine the effect of metronomic chemotherapy on the survival rates of cancer patients when compared to that of standard chemotherapy drugs in different cancer types. It includes advanced ovarian and prostate carcinomas as well as certain types of hematological cancers. Earlier studies showed that anti-angiogenic drugs can improve the effects of some standard chemotherapy treatments.

Does Metronomic Chemotherapy Enhance the Effect of Radiation?

Vasculature and the hypoxic state of the tumor are important predictive factors for the effectiveness of radiotherapy. Agents that have anti-angiogenic properties can enhance the radiosensitivity of the tumors, and it is true for metronomic therapy as well. When given in combination with metronomic therapy, radiation can overcome the hypoxia-related resistance of the tumor.

Can Metronomic Chemotherapy reduce the side effects of Chemotherapy and Radiation?

High doses of chemotherapy drugs are frequently associated with many adverse effects, that include:

  • Acute myelosuppression
  • Damage to the intestinal mucosa hair loss
  • Nausea
  • Mucositis
  • Long-term renal, cardiac, neurological and reproductive consequences.

All these side effects need co-administration of agents such as antiemetics and growth factors to counteract the harmful effects of chemotherapy and accelerate the process of recovery, which adds to the financial burden of the chemotherapy.

The Influence of Metronomic Chemotherapy on the Immune System:

It has been established that in some cases, low doses of chemotherapy can stimulate the immune system of the body. It makes it a potentially helpful therapy to be used in combination with tumor vaccines or other types of immune therapies. Some studies have also proved that in preclinical models, metronomic chemotherapy along with Cyclophosphamide can enhance the efficacy of immunotherapeutic vaccines.

Does Metronomic Chemotherapy Increase Quality of Life and Survival Rate?

A large amount of data is available supporting the effectiveness of metronomic therapy as a tool to fight against cancer cells. Frequent administration of chemotherapy at doses significantly lower than maximum tolerated doses has been proven to be associated with prolonging the lives of patients with end-stage or metastatic disease, in comparison to the highest possible doses of chemotherapy, that cause life-threatening levels of toxicity.

Summary:

Metronomic chemotherapy

It is a name given to a practice of giving low doses of chemotherapy more frequently rather than giving a single high dose of these cytotoxic agents, the aim being to minimize the toxicity.

Effects of Metronomic chemotherapy

When given in low doses, it is well tolerated by patients who are weak or have low blood counts. The efficacy of this treatment seems to increase when administered with certain anti-angiogenic agents.

Metronomic chemotherapy and conventional chemotherapy

Most chemotherapeutic agents are designed to kill the cells rapidly using high doses with long breaks to allow recovery from potential side effects. Metronomic therapy is based on the idea of administering small doses of chemotherapy drugs, which not only have less harmful effects but have antitumor effects also.

Metronomic chemotherapy and radiotherapy

Metronomic therapy enhances the efficacy of radiotherapy by reducing the hypoxia-induced resistance and vascularity of the tumors.

Cancer types where studies proven the positive effects of this treatment

Metronomic therapy has been proven to be associated with better results in widespread or metastatic tumors. Such as metastatic lung, breast lung cancers, hematological cancers, and pediatrics cancers like neuroblastoma, rhabdomyosarcoma, and Wilms tumor.

 

References:

  1. Metronomic chemotherapy: changing the paradigm that more is better
  2. Metronomic chemotherapy
  3. Understanding Metronomic chemotherapy
  4. Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncology clinic

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