Lung Cancer

Treatments: Best Practices

Lung cancer is typically found in two forms, non-small cell carcinoma and small cell carcinoma. Depending on the type and stage of the cancer progression, treatment can vary. Below is a brief description of the both types and the stages associated with them:

Non-Small Cell Lung Carcinoma (NSCLC)

This type of lung cancer accounts of 85% of the lung cancers.

❖      Stage 1: cancer is localized to the lungs. It has not yet metastasized to the lymph nodes.

❖      Stage 2: cancer has metastasized to nearby lymph nodes.

❖      Stage 3: cancer has metastasized to the lymph nodes in the middle of the chest.

❖      Stage 4: cancer has metastasized to both lungs or to other organs.

Small Cell Lung Carcinoma (SCLC)

This type of cancer accounts for the other 15% of lung cancer cases. It is called small cell carcinoma because the tumor is abnormally small. SCLC is a highly malignant form of lung cancer and its treatment options vary.

❖      Limited Stage: cancer is found on one side of the chest and nearby lymph nodes

❖      Extensive Stage: metastasize to other organs.

Prevention

First and foremost, many cases of lung cancer can be avoided by staying away from smoking. It is well known that cigarette smoke contains many carcinogens that puts the smoker at an elevated risk of cancer. In addition, it has been shown that smokers who have quit smoking after being diagnosed with lung cancer are much more successful in beating it.

Erlotinib (Tarceva)

This drug is a monoclonal antibody and an epidermal growth factor receptor (EGFR) inhibitor. The EGFR receptor is responsible for downstream signaling pathways involved in cell proliferation and DNA synthesis. In fact, many cancer drugs on the market take advantage of this signaling pathway.Therefore, inhibiting this receptor results in inhibition of cell growth and induction of apoptosis (programmed cell death). It is sold under the trade name Tarceva and is a product of Astellas pharma.

Bevacizumab (Avastin)

Avastin is used for a wide variety of cancers, but it used mostly as a first line treatment for advanced, recurrent or metastatic non-small cell lung cancer. It works by binding to VEGF (vascular endothelial growth factor), not allowing it to bind to its receptor. This prevents cell proliferation and angiogenesis. When used in cancer patients, this drug essentially starves cancer cells of nutrients since blood vessels cannot form. In many clinical trials being conducted now, Avastin is prescribed in conjunction because of its proven track record.

Crizotinib (Xalkori)

The FDA gave this drug accelerated approval in 2011. It is used to treat advanced or metastatic non-small cell lung cancer. Xalkori works by inhibiting the oncogene called ROS1. This oncogene codes for a particular enzyme that is highly expressed in lung cancer cells. The enzyme is ultimately involved in oncogenesis via kinase cascades. Xalkori binds competitively to the ATP binding domain of the enzyme, thus rendering it inactive. In addition to its uses in lung cancer, Xalkori has been shown to be effective in some cases of lymphoma.

Chemotherapy

As with most cancers, lung cancer can be treated with cycles of chemotherapy. When it is used before surgery (neoadjuvant therapy), its purpose is to shrink the tumor to increase the likelihood of success of the surgery. It can be used after surgery (adjuvant therapy) to kill any of the remaining cancerous cells left behind. In advanced cases, chemotherapy is coupled with radiation therapy as the main source of treatment. There are many chemotherapy drugs available on the market including: Cisplatin, Carboplatin, Taxol, Abraxane, Taxotere, Gemzar, Navelbine, Camptosar, Etoposide, Vinblastine, and Alimta. Especially for non-small cell cancers, two of these chemo drugs will be used in conjunction and often Avastin will be prescribed in adjunct.

Radiation Therapy

There are several options when choosing radiation therapy. External beam radiation therapy (EBRT) is primarily used to treat the initial lung cancer or if it has spread to other organs, although it is not used as often as new treatments.

Newer techniques, such as 3D conformal radiation therapy accurately maps the tumor. This targeted therapy decreases the likelihood that healthy tissue gets damaged by the radiation. A more advanced form of this treatment is called intensity modulated radiation therapy which is completely computer driven. This makes it very precise and useful in vital areas like the spine.

Perhaps the best form of radiation for lung cancer is brachytherapy. A pellet of radioactive material is inserted into the cancerous tissue via a bronchoscope. The pellet is only left in the lung for a short period of time and is then removed so that healthy tissue is not damaged. Seed particles are left behind for a longer term release of radiation which weakens over time. This type of therapy should only be administered once.

Treatment for Small Cell Carcinoma

SCLC does not respond well to surgery, so treatments such as chemotherapy or radiation therapy are better options. If the treatments described above does not work, or if the cancer recurs, seeking clinical trials is another option.

Research Pipeline

MPDL3280A

This drug is an antibody produced by the Roche group that has shown particular success in smoking patients. In early clinical trials, 26% of smokers saw significant tumor shrinkage, whereas only 10% of non-smokers saw a significant improvement. This statistic is important because most cases of non-small cell lung cancer are caused by smoking. Treatment that can specifically target these cancers can help save many lives.

The antibody was engineered to target PD-L1 (programmed cell death ligand 1), which basically suppresses the immune system. Tumors exploit this mechanism to “hide” from the body’s immune system. By inhibiting PD-L1, T-cells can be active again and attack the cancer cell.  By recruiting the body’s own defense to combat the cancer, a more sustained effect could be seen. Genentech is currently recruiting for phase II trials.

AUY992

This is a particularly interesting drug currently being developed by Novartis. It acts by inhibiting the chaperone HSP90, which is vital to normal cell growth and division. Novartis believes that targeting this chaperone could be a viable treatment option because cancer cells exist in a very stressful environment and depend on this chaperone to perform its daily operations. Inhibiting its function will kill the cancerous cells. A phase II trial is underway to confirm this mechanism of action in NSCLC, breast, and gastric cancer.

Buparlisib (BMK120)

This drug also being developed by Novartis but targets the PI3K pathway. It is part of a pivotal signaling pathway that is important in angiogenesis and cellular metabolism. It seems that abnormal activation of this pathway leads to initiation and survival of tumors. By inhibiting this pathway, cancer cell proliferation is stopped and cell death is induced. Buparlisib is being tested in phase II clinical trials.

SCLC Drug Candidates

Because current treatment of SCLC is limited to chemotherapy and radiation therapy, research into new treatments are moving toward immunotherapies. One drug being studied is nintedanib, which is an angiokinase inhibitor that functions similarly to Avastin. The family of angiokinase inhibitors have been used to treat a wide variety of solid tumors, so the hope is that it can be an effective treatment of SCLC.

Another drug being researched is sunitinib (Sutent) which is a receptor tyrosine kinase inhibitor previously used to treat many types of cancer including pancreatic, gastrointestinal, leukemia, and renal cancers. Several studies in which this drug was combined with current chemotherapy drugs are underway or have completed and the results are pending.

The drug ipilimumab (Yervoy) which is used to treat melanoma, is also being studied. It is being combined with current chemo drugs and is targeting extensive SCLC.

Centers of Excellence

❖      Moffitt Cancer Center (Florida) – over the past 5 years have acquired more than 10 million dollars in Specialized Programs of Research Excellence (SPORE) grant money for lung cancer research.

❖      Norwalk Hospital (Connecticut)

❖      MD Anderson Cancer Center (Texas) – also received SPORE grant

❖      National Lung Cancer Mutation Consortium

➢      16 centers across the US

➢      University of Colorado Cancer Center Thoracic Oncology Program is notable

❖      Sloan-Kettering Cancer Center (New York)

❖      Dana Farber Cancer Center (Massachusetts)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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