Metronomic Chemotherapy-An Arsenal!

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“We have assisted with all plausible prevalent medical facilities to the cancer patient. There is nothing more we can do. We are sorry.”

Some of us have heard these frightful words from able bodied, world-class oncologists who hand over our loved ones into the hands of the Almighty and pray for a least pained exit. Terminally ill cancer patients (adults or children) have little choice of medicines which can aid to prolong their lifetime as they become resistant to the treatment engaged.

We spend billions of money to safe guard fragile boundaries of our countries; fund domestic and international acts of terror; lobby for the acceptance of genetically modified food and finance trips to Mars. However, we need a lot more of financial investments to attain victory in our war against cancer. Cancer is a disease of unregulated mass of cells wherein the natural cycle of cell death is compromised leading to the formation of tumour. A neoplastic growth may be benign, premalignant or malignant. An identified tumour may be removed through surgery followed by various rounds of radiation and chemotherapy to eradicate remaining tumour cells. On the other hand in numerous cases on successive rounds of therapy the tumour aggressively metastasize into other organs ultimately causing demise.

The bygone decades has seen many scientists who have challenged their scientific acumen to comprehend biological mechanisms undertaken by cancerous cells in evading cell death and promote multi drug resistance. Cancer patients often need an amendment of chemo drugs due to the phenomena of acquired chemo resistance. Present treatment modalities used often act upon the non-cancerous cells and actively dividing tumour cells alike. However, due to an inefficient removal of circulating tumour cells most often it results in reappearance of tumour and relapse of the disease. Hence, the need of the hour is a combinatorial method to prolong life span of the patient.  

The traditional chemotherapy treatment regimens use chemotherapeutic drugs which act against epithelial growth factor receptors and vascular epidermal growth factor receptors in order to prevent proliferation of circulating cancer cells and metastasis via inactivation of cellular signalling pathways. Both healthy cells and tumour cells are killed indiscriminately. In this mode of chemotherapy clinicians administer high doses of chemo drugs for a limited number of cycles onto patients: to hinder acquired chemo resistance against the drug and harming the organs. Patients’ are subjected to a drug-free interval between successive cycles of chemotherapy which results in revival of healthy and cancer cells equally. Numerous retrospective analyses have revealed that chemotherapy medicines may limit growth of tumour volume but it may also promote the assembly of endothelial cells to form blood vessels in the tumour (angiogenesis) and metastasis. Thus, these regimens haven’t been fool proof and the

need of the hour is for an alternative therapeutic regimen.

A prominent alternative therapy which is gaining recognition to mitigate chemo resistance is metronomic chemotherapy. The concept of metronomic strategy was first tested by Dr. Timothy Browder in Harvard Medical School, USA.  Hanahan and his colleagues from the University of California, San Francisco has defined metronomic chemotherapy: “chronic administration of chemo therapeutic agents at relatively low, minimally toxic doses, and with no prolonged drug-free breaks”. This method uses the same drugs as in the traditional chemotherapy but in different combinations and in low doses on a regular basis. Therefore, consistent short exposures of the medicine hamper growth of endothelial cells: new blood vessels are not formed in the tumour. Consequently angiogenesis is hampered. In turn this strategy induces hypoxia and starves tumour cells off nutrients. Metronomic chemotherapy is a multi targeted therapy: negates migration and proliferation of cancerous cells, induces apoptosis, increases endogenous level of anti-angiogenic factors and enhances anticancer immune response in the human body.

The propensity for critical scrutiny of this strategy is underway through numerous retrospective analyses of clinical trials which have revealed a mixed reaction. For instance, research has revealed that adults prescribed to palliative care that are pre-treated with chemotherapy and are at an advanced stage of colorectal cancer, gastric cancer, vascular tumours have responded to metronomic chemotherapy successfully. Also, children suffering from medulloblastoma have shown a good response to metronomic regimen of temozolomide with radiotherapy. Nonetheless, metronomic chemotherapy in some glioblastoma and advanced stage renal cancer patients’ did not significantly enhance their chances of survival.

The high dose of medicines when injected into patients causes numerous grave side effects due to loss of healthy cells. Repetitive low dose of chemotherapy may cause side effects like nausea, anaemia, neutropenia, fatigue and leucopoenia to dwindle. Metronomic chemotherapy is usually given to patients who cannot bear high doses of chemotherapy. It may be an alternative mode of treatment for patients who have acquired chemo resistance and are prescribed to palliative care. Metronomic chemotherapy may grant that each cancer victim desires: TIME.   

Numerous hospitals like the Oasis of Hope Hospital and Northridge Hospital Medical Centre in the United States of America are trying to prolong the lives of cancer victims by administering metronomic chemotherapy. In India, team lead by Dr. S. D. Banavali at Tata Memorial Hospital, Department of Medical Oncology has assessed the feasibility of using metronomic chemotherapy for palliation in oral cancer. Their research indicates a clinical benefit rate of 66.67% and larger clinical trials are needed to substantiate further in other cancers.

Metronomic chemotherapy is a less traversed route to combat cancer. Consequently, ample clinical trials in different ethnic populations are warranted before it may be globally claimed as a gold standard parapet against cancer. Nevertheless, for those friends and families who are in a dire-famine like situation looking for alternative modes of treatment to keep their loved one alive- metronomic chemotherapy may be an option worth exploring.