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18 November, 2019 00:00 00 AM

Changing paradigm in management of lung cancer

65DoctorsNewsletters
Changing paradigm in management of lung cancer

Lung cancer in Asia is a major public health problem as it contributes to high morbidity and mortality. The incidence of smoking continues to rise in many parts of Asia and there is no signs of reduction in incidence of lung cancer.

Advanced lung cancer remains an incurable cancer and fortunately the advances in understanding of staging, pathology, molecular biology and personalised medicine have changed the landscape of treatment and outcome of many patients with advanced disease. We are beginning to appreciate that the response and outcome of patients with some lung cancer are dependent on gender, smoking history and ethnicity. Fortunately research in the past decade has shown that East Asians with advanced lung cancer and who do not smoke have better outcome than similar population in other countries.

Before 2004, most oncologists approach patients with lung cancer in simplistic ways:-

extensive stage small cell lung cancer (SCLC) was treated with palliative cytotoxic drugs, whilst limited stage SCLC was treated with chemotherapy with concurrent chemoradiation and possible prophylactic cranial irradiation early stage non-small cell lung cancer (NSCLC) was offered surgery with or without radiation and advanced stage NSCLC was given palliative chemotherapy with occasional radiation for symptom control In 2014, the approach to management of SCLC has not changed much but there has been a major paradigm shift in managing advanced stage NSCLC.

The major challenge in managing advanced NSCLC is getting adequate amount of tumour tissue from biopsies for various immunostains to define the type of NSCLC and molecular biomarkers. These are important to plan on personalising the type of treatment for these patients.

On this issue of lung cancer, there are lung cancer experts to define the importance of pathological classification to define on type of cytotoxic drugs or targeted therapies, technological advances in computerised radiation therapies, advances in chemotherapy and targeted therapies and glimpses into role of immunotherapy of lung cancer in future.

The future of lung cancer research looks promising but remains challenging as we make small but meaningful advances. The improvement in disease free interval and overall survival of advanced NSCLC in the past decade have been shown in many series.

However, the cost of new therapies and the burden on healthcare cost are formidable challenges for individuals and society at large.

Understanding how targeted therapies in non-small lung cancer work

The past decade has seen researchers translate the biology of lung cancer cells into developing new drugs that specifically target these changes. These targeted drugs work differently from standard cytotoxic chemotherapy drugs. They sometimes work when cytotoxic drugs don’t, and they often have different (and less severe) side effects. At this time, they are most often used for advanced lung cancers, either along with chemotherapy or by themselves.

Drugs that target tumour blood vessel growth (angiogenesis)

For tumors to grow, they must form new blood vessels to keep them nourished. This process is called angiogenesis. Some targeted drugs, called angiogenesis inhibitors, block this new blood vessel growth.

Bevacizumab is an angiogenesis inhibitor used to treat advanced non-small cell lung cancer. It is a monoclonal antibody (a man-made version of a specific immune system protein) that targets vascular endothelial growth factor (VEGF), a protein that helps new blood vessels to form. This drug is often used with chemotherapy for a time.

Ramucirumab is another angiogenesis inhibitor that can be used to treat advanced non-small cell lung cancer. VEGF has to bind to proteins called receptors to act.  This drug is also a monoclonal antibody that targets a certain type of receptor for VEGF.  Nintedanib is a new oral angiogenesis inhibitor that shows promising results in combination with chemotherapy for advanced lung cancer. These drugs help stop the formation of new blood vessels.

These drugs can have side effects that are different from (and may add to) those of chemotherapy. Some of these can be serious, and can include problems with bleeding as well as blood clots and hypertension. Rarely, these drugs can cause a hole to form in the intestine or stomach (called a perforation). These drugs can also cause problems with wound healing and so need to be stopped prior to surgery.

Because of the risks of bleeding, these drugs aren’t used in patients who are coughing up blood or who are on drugs considered blood thinners.

The risk of serious bleeding in the lungs is higher in patients with the squamous cell type of lung cancer, which is why most current guidelines do not recommend using bevacizumab in patients with this type of lung cancer.

Drugs that target EGFR

Epidermal growth factor receptor (EGFR) is a protein found on the surface of cells. It normally helps the cells to grow and divide. Some NSCLC cells have too much EGFR, which causes them to grow faster. Drugs that target EGFR used to treat non-small cell lung cancer (NSCLC) include: i ) Erlotinib ii ) Gefitinib iii ) Afatinib.

Erlotinib, gefitinib and afatinib block the signal from EGFR that tells cells to grow. These are oral tablets and they can be used alone (without chemotherapy) as the first treatment for advanced NSCLC that have certain mutations in the EGFR gene. These are more common in women, Asian people who haven’ t smoked.

Common side effects of these drugs include: Skin problems, Diarrhoea, Mouth sores, Loss of appetite.

Skin problems can include an acne-like rash on the face and chest, which in some cases can lead to skin infections.

Drugs that target the ALK gene

About 5 to 8% of NSCLCs have been found to have a rearrangement in a gene called ALK or EML4-Alk. This change is most often seen in non-smokers (or light smokers) who have the adenocarcinoma subtype of NSCLC.

The ALK gene rearrangement produces an abnormal ALK protein that causes the cells to grow and spread. Drugs that target ALK gene include: i ) Crizotinib ii ) Ceritinib iii ) Alectinib. These drugs block the abnormal ALK protein and can shrink tumours in patients whose lung cancers have the ALK gene rearrangement.  Although they can work after chemotherapy has stopped working, they are often used instead of chemotherapy in people whose cancers have the ALK gene rearrangement.

All these drugs are taken as oral pills. Common side effects include: Nausea and vomiting, Diarrhoea, Constipation, Fatigue, Change in vision.

Some side effects can be severe, such as low white blood cell counts, lung inflammation, liver damage, and heart rhythm problems.   

These targeted therapies will continue to evolve as we find new targets and companion diagnostic markers for personalizing the use of these drugs. (Reprint)

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Editor : M. Shamsur Rahman

Published by the Editor on behalf of Independent Publications Limited at Media Printers, 446/H, Tejgaon I/A, Dhaka-1215.
Editorial, News & Commercial Offices : Beximco Media Complex, 149-150 Tejgaon I/A, Dhaka-1208, Bangladesh. GPO Box No. 934, Dhaka-1000.

Editor : M. Shamsur Rahman
Published by the Editor on behalf of Independent Publications Limited at Media Printers, 446/H, Tejgaon I/A, Dhaka-1215.
Editorial, News & Commercial Offices : Beximco Media Complex, 149-150 Tejgaon I/A, Dhaka-1208, Bangladesh. GPO Box No. 934, Dhaka-1000.

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