What is the treatment for lung cancer? (Part 3)

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Chemotherapy: Both NSCLC and SCLC may be treated with chemotherapy. Chemotherapy refers to the administration of drugs that stop the growth of cancer cells by killing them or preventing them from dividing. Chemotherapy may be given alone, as an adjuvant to surgical therapy, or in combination with radiotherapy. While a number of chemotherapeutic drugs have been developed, the class of drugs known as the platinum-based drugs have been the most effective in treatment of lung cancers.

Chemotherapy is the treatment of choice for most SCLC, since these tumors are generally widespread in the body when they are diagnosed. Only half of people who have SCLC survive for four months without chemotherapy. With chemotherapy, their survival time is increased up to four- to fivefold. Chemotherapy alone is not particularly effective in treating NSCLC, but when NSCLC has metastasized, it can prolong survival in many cases.

Chemotherapy may be given as pills, as an intravenous infusion, or as a combination of the two. Chemotherapy treatments usually are given in an outpatient setting. A combination of drugs is given in a series of treatments, called cycles, over a period of weeks to months, with breaks in between cycles. Unfortunately, the drugs used in chemotherapy also kill normally dividing cells in the body, resulting in unpleasant side effects. Damage to blood cells can result in increased susceptibility to infections and difficulties with blood clotting (bleeding or bruising easily). Other side effects include fatigue, weight loss, hair loss, nausea, vomiting, diarrhea, and mouth sores. The side effects of chemotherapy vary according to the dosage and combination of drugs used and may also vary from individual to individual. Medications have been developed that can treat or prevent many of the side effects of chemotherapy. The side effects generally disappear during the recovery phase of the treatment or after its completion.

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Targeted therapy: Molecularly targeted therapy involves the administration of drugs that have been identified to work in subsets of patients whose tumors have specific genetic changes (driver mutations) that promote tumor growth.

EGFR-targeted therapies: The drugs erlotinib (Tarceva), afatinib (Gilotrif), and gefitinib (Iressa) are so-called targeted drugs that more specifically target cancer cells, resulting in less damage to normal cells than general chemotherapeutic agents. Erlotinib, gefitinib, and afatinib target a protein called the epidermal growth factor receptor (EGFR) that is important in promoting the division of cells. The gene encoding this protein is mutated in many cases of non-small cell lung cancer, creating a mutation that encourages tumor growth. Mutations in the EGFR gene are more common in cancers in women and in people who have never smoked. Drugs that target the EGFR receptor sometimes stop working after a time, which is known as resistance to the drug. Resistance often occurs because the cancer has developed a new mutation in the same gene, and a common example of this is the so-called EGFR T790M mutation. Some newer EGFR-targeted drugs also work against cells with the T790M mutation, including osimertinib (Tagrisso). Necitumumab (Portrazza) is another drug that targets EGFR. It can be used along with chemotherapy as the first treatment in people with advanced NSCLC of the squamous cell type.

Other targeted therapies: Other targeted drugs are available that target other driver mutations. These other targeted therapies include the ALK tyrosine kinase inhibitor drugs crizotinib (Xalkori), alectinib (Alecensa), brigatinib (Alunbrig), and ceritinib (Zykadia) that are used in patients whose tumors have an abnormality of the ALK gene as the driver mutation. Some of these drugs may also be helpful for people whose cancers have an abnormality of the gene known as ROS1.

The gene known as BRAF can also be abnormal in lung cancers causing the production of BRAF protein that promotes the cancer’s growth. Dabrafenib (Tafinlar) is a type of drug known as a BRAF inhibitor and attacks the BRAF protein directly. Trametinib (Mekinist) is known as a MEK inhibitor because it attacks MEK proteins, which are related to BRAF proteins. These may be used for patients with tumors that have abnormal BRAF genes.

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Other attempts at targeted therapy include drugs known as antiangiogenesis drugs, which block the development of new blood vessels within a cancer. Without adequate blood vessels to supply oxygen-carrying blood, the cancer cells will die. The antiangiogenic drug bevacizumab (Avastin) has also been found to prolong survival in advanced lung cancer when it is added to the standard chemotherapy regimen. Bevacizumab is given intravenously every two to three weeks. However, since this drug may cause bleeding, it is not appropriate for use in lung cancer patients who are coughing up blood, if the lung cancer has spread to the brain, or in people who are receiving anticoagulation therapy (“blood thinner” medications). Bevacizumab also is not used in cases of squamous cell cancer because it leads to bleeding from this type of lung cancer. Ramucirumab (Cyramza) is another angiogenesis inhibitor that can be used to treat advanced non-small cell lung cancer.

Immunotherapy: Immunotherapy may be an effective option for some patients with advanced lung cancers. Immunotherapy drugs work by strengthening the activity of the immune system against tumor cells. The immunotherapy drugs nivolumab (Opdivo) and pembrolizumab (Keytruda) were approved by the U.S. FDA in 2015 for the treatment of lung cancer. These drugs are checkpoint inhibitors that target checkpoints or areas that control the immune response and promote the immune response. These two drugs target the PD-1 protein, which strengthens the immune response against the cancers. Atezolizumab (Tecentriq) is a drug that targets PD-L1, a protein related to PD-1 that is found on some tumor cells and immune cells.

Radiofrequency ablation (RFA): Radiofrequency ablation is being studied as an alternative to surgery, particularly in cases of early stage lung cancer. In this type of treatment, a needle is inserted through the skin into the cancer, usually under guidance by CT scanning. Radiofrequency (electrical) energy is then transmitted to the tip of the needle where it produces heat in the tissues, killing the cancerous tissue and closing small blood vessels that supply the cancer. RFA usually is not painful and has been approved by the FDA for the treatment of certain cancers, including lung cancers. Studies have shown that this treatment can prolong survival similarly to surgery when used to treat early stages of lung cancer but without the risks of major surgery and the prolonged recovery time associated with major surgical procedures.

Experimental therapies: Since no therapy is currently available that is absolutely effective in treating lung cancer, patients may be offered a number of new therapies that are still in the experimental stage, meaning that doctors do not yet have enough information to decide whether these therapies should become accepted forms of treatment for lung cancer. New drugs or new combinations of drugs are tested in so-called clinical trials, which are studies that evaluate the effectiveness of new medications in comparison with those treatments already in widespread use. Newer types of immunotherapy are being studied that involve the use of vaccine-related therapies that attempt to utilize the body’s immune system to directly fight cancer cells. Lung cancer treatment vaccines are being studied in clinical trials.