Types of Medications for Non-Small Cell Lung Cancer

Medications for non-small cell lung cancer (NSCLC) refer to various classes of prescription drugs used in the treatment of four stages of NSCLC. NSCLC medications are used to:

• Destroy cancer cells
• Prevent or slow cancer growth and/or spread (metastasis)
• Prevent relapse of cancer
• Prolong the period of remission
• Alleviate pain and other cancer symptoms
• Treat cancer medication’s side effects
• Prolong survival and quality of life

Each type of medication used in the treatment of NSCLC works in a unique way to stop or slow down the progression of cancer. Most people require treatment with more than one type of medications.

Chemotherapy drugs such as carboplatin or docetaxel are often an integral part of the treatment. Chemotherapy destroys cancer cells, but also damages healthy cells. Antiemetic medications are routinely prescribed with chemotherapy to prevent the primary side effects such as nausea, vomiting and diarrhea.  

Targeted therapy for treating NSCLC are small molecule drugs and monoclonal antibodies, which do not kill cancer cells, but alter specific cancer cell mechanisms to inhibit their growth and proliferation. Monoclonal antibodies also help enhance the immune system’s ability to fight cancer.

Other medications typically used in NSCLC treatment include pain relievers, corticosteroids to prevent inflammation, antibiotics to prevent infections, and other medications to treat specific cancer symptoms or medication side effects.

Non-small cell lung cancers are certain types of cancers that start in different regions of the lungs. Cancer is an uncontrolled proliferation of abnormal cells which evade the regulatory mechanisms that control the growth of cells.

Cancers arise from genetic mutations which enable cancer cells to grow, divide, migrate and avoid programmed death (apoptosis) that normal cells undergo when damaged or no longer needed.

Cancers grow into malignant masses of tissue known as tumors, lesions or nodules and can spread to other parts of the body. Lung cancers may also arise due to metastasis from cancers in other parts of the body, such as breast, kidneys or pancreas. 

In these cases, the cancerous lung tissue is identified by the tissue of cancer origin, for example, “breast cancer metastasized to the lungs.”

The two major types of lung cancers are:

• Small cell lung cancer (SCLC): Small cell lung cancer, also known as oat cell carcinoma, is an aggressive type of cancer that grows and spreads rapidly. SCLC usually starts in the respiratory tubes (bronchi) of the lungs, in the middle of the chest. SCLC responds well to radiation and chemotherapy, but for most people, this cancer usually returns. SCLC is of two types:
  • Small cell carcinoma
  • Combined small cell carcinoma
• Non-small cell lung cancer (NSCLC): Lung cancers other than small cell lung cancer are grouped into non-small cell lung cancers, because their treatments and prognoses are generally similar. Approximately 85% of lung cancers are non-small cell lung cancers.

There are a few other types of lung cancers such as carcinoid tumors, sarcomas and hamartomas, a benign type of tumor, but these are uncommon. This article will emphasize NSCLC.

The main types of non-small cell lung cancer are:

• Adenocarcinoma: Adenocarcinoma is a type of cancer which starts in the lung cells that secrete mucus. It usually occurs in the peripheral lung regions. 
  • Adenocarcinoma in situ is a subtype that is localized and has better prognosis with treatment than other types.
• Squamous cell carcinoma: Squamous cell carcinoma starts in the central regions of the lung in the squamous cells, a flat type of cells that line the inner walls of the lung’s airways.
• Large-cell (undifferentiated) carcinoma: Large-cell carcinoma can start anywhere in the lung and can spread fast. A subtype known as large-cell neuroendocrine carcinoma, which is similar to small cell lung cancer, can grow and spread rapidly.

NSCLC may often produce few to no symptoms in early stages. In approximately 55% of people, the cancer has metastasized to distant parts of the body at the time of diagnosis. The symptoms of NSCLC depend on the location of the primary tumor and the regions of metastasis. The most common symptoms of NSCLC from the primary tumor include:

• Persistent cough
• Coughing up blood (hemoptysis)
• Shortness of breath
• Wheezing
• Hoarseness of voice
• Chest pain, particularly with deep breaths, coughing or laughing
• Lung infections like pneumonia, lung inflammation and fluid collection (pleural effusion) in the lungs

Symptoms of NSCLC metastasis depend on the region of metastasis, but common symptoms include:

• Unexplained weight loss
• Headaches, dizziness or balance problems
• Bone pain
• Nausea and vomiting
• Numbness or weakness

Tobacco smoking is the primary cause for lung cancers, accounting for 78% in men and 90% in women. Approximately 25% of lung cancers in nonsmokers are caused by secondhand (passive) smoking. Other causes of lung cancer include:

• Exposure to radon, an inert gas produced by uranium decay
• Asbestos exposure
• Halogen ether exposure
• Chronic interstitial pneumonitis, a disorder which affects tissue in the space between the air sacs (alveoli) in the lungs
• Inorganic arsenic exposure
• Radioisotope exposure, ionizing radiation
• Atmospheric pollution
• Chromium, nickel exposure
• Vinyl chloride exposure

The choice of treatment for non-small cell lung cancer depends on its stage at the time of diagnosis. Surgery to remove the cancerous portion may be the only treatment required for some people with NSCLC stage I. Most people, however, need a combination of different therapies.

Early detection and treatment improve the prognosis for remission from NSCLC. People in advanced metastatic stages of NSCLC or for whom standard treatments have not succeeded in eliminating the cancer have the option of enrolling in clinical trials for new treatments.

Treatments for NSCLC include the following:

Surgery

Surgery involves surgical removal (resection) of a part of, or an entire lung, to get rid of the cancer. Some of the lymph nodes in the lung region are also usually removed to prevent cancer from spreading.

Surgery may be performed as an open surgery or a minimally invasive video-assisted thoracoscopic surgery (VATS) with small incisions, using a lighted camera (thoracoscope) and tiny instruments inserted through a flexible tube into the chest.

The types of surgery include:

• Lobectomy: Lobectomy is the removal of an entire lobe of the lung. There are five lobes in the lungs, three in the right and two in the left.
• Wedge resection: Wedge resection is the removal of just the tumor, along with a margin of healthy cells.
• Segmentectomy: Segmentectomy is removal of a portion of the lung in which the tumor is present, when it is not possible to remove an entire lobe.
• Pneumonectomy: Pneumonectomy is the removal of an entire lung, mostly performed when the tumor is close to the center of the chest.

Radiation therapy

Radiation therapy is the use of high energy X-rays to destroy cancer cells, typically consisting of several sessions of treatment. Radiation therapy cannot be used to treat widespread cancer because it can only destroy cancer cells directly in the path of the radiation beam. Radiation therapy can also damage healthy cells in its path.

Radiation therapy may be a useful alternative treatment for some people with NSCLC stage I, who cannot have surgery for any reason. Radiation therapy can also be used as an adjuvant therapy with surgery or chemotherapy.

Medications

Medications are systemic therapies to destroy cancer cells, and/or halt or slow the growth and multiplication of cancer cells. Most people require treatment with a combination of different types of medications.

NSCLC medications are individualized depending on the type and stage of the cancer, age and overall health of the patient. Medications may be administered through various routes such as oral tablets, injections or intravenous infusions.

Medications for NSCLC are of three major types and each type works in a different way to combat cancer growth and spread.

• Chemotherapy: Chemotherapy drugs are toxic compounds that directly destroy cancer cells, but they can also damage healthy cells and cause multiple side effects. Drugs given to treat side effects include antiemetics and corticosteroids. Chemotherapy drugs are typically administered in three to six weekly cycles which include time to recover from the side effects.
• Targeted therapy: Targeted therapies mostly use medications known as small molecule drugs. Small molecule drugs are tiny particles that target specific proteins or cell-signaling pathways which contribute to cancer growth and metastasis. Targeted therapy limits damage to healthy cells and usually has fewer side effects than chemotherapy.
• Immunotherapy: Immunotherapy medications are genetically engineered protein molecules known as monoclonal antibodies, which enhance the immune system’s activity against cancer cells.

Chemotherapy

Chemotherapy medications are lethal to cancer cells because they target cells which are in the phases of growth and division. Chemotherapy affects all fast-growing cells including healthy cells of skin, hair, bone marrow and intestines. Healthy cells may recover over a period of time, but cancer cells die because of their genetic mutations.

Chemotherapy is currently used mostly as an adjuvant (secondary) therapy for NSCLC along with surgery or radiation, because it is only moderately effective for NSCLC. Chemotherapy may be administered as a palliative therapy in some patients with advanced stages of NSCLC.

A combination of chemotherapy medications may be used in NSCLC treatment because each drug interferes with the cell growth in different phases of the cell cycle, increasing the odds of killing/preventing more cancer cells. Following are FDA-approved chemotherapy medications for treatment of NSCLC:

• Carboplatin
• Vinorelbine tartrate
• Paclitaxel
• Paclitaxel protein bound (Abraxane)
• Gemcitabine hydrochloride (Gemzar)
• Docetaxel (Taxotere)
• Pemetrexed disodium (Alimta)
• Doxorubicin hydrochloride

FDA-approved combination chemotherapy medications are:

• Carboplatin/paclitaxel
• Gemcitabine/cisplatin
• Chemotherapy medications used off-label for NSCLC include:
• Cisplatin
• Cyclophosphamide (Cytoxan)
• Etoposide

Targeted therapy

Targeted therapy consists of several classes of medications that do not kill cancer cells, but inhibit their growth and spread. Targeted therapy medications block the activity of specific proteins which help cancer cells grow, divide, migrate to other parts, differentiate into specialized cells and evade programmed cell death. 

Most targeted therapy medications are small molecule drugs, except for a few which are monoclonal antibodies (synthetic antibodies that attack cancer cells). 

Each class of targeted medication inhibits the activity of a specific protein with aberrant behavior, caused by mutation in the gene that encodes it. Some medications are effective for more than one gene mutation.

Following are FDA-approved targeted therapies for NSCLC based on various proteins and cell mechanisms that help cancer growth and metastasis:

• Anaplastic lymphoma kinase (ALK) inhibitors
  • Crizotinib (Xalkori) -- ALK and ROS1 gene mutations
  • Ceritinib (Zykadia)
  • Alectinib hydrochloride (Alecensa)
  • Brigatinib (Alunbrig)
  • Lorlatinib (Lorbrena)
• Epidermal growth factor receptor (EGFR) inhibitors
  • Small molecule drugs
    • Osimertinib mesylate (Tagrisso)
    • Gefitinib (Iressa)
    • Erlotinib hydrochloride (Tarceva)
    • Afatinib dimaleate (Gilotrif)
    • Dacomitinib (Vizimpro)
  • Monoclonal antibodies
    • Necitumumab (Portrazza)

BRAF gene mutations (gene mutation in cell signals and cell growth)

• Dabrafenib mesylate (Tafinlar)
• Trametinib dimethyl sulfoxide (Mekinist)

Tropomyosin receptor tyrosine kinase (TRK) inhibitors

• Entrectinib (Rozlytrek) -- inhibits TRK proteins, and ROS1 and ALK gene mutations
• Larotrectinib sulfate (Vitrakvi) -- solid tumors with NTRK fusion gene mutation
• Capmatinib hydrochloride (Tabrecta) -- mesenchymal-epithelial transition (MET) exon 14 skipping mutation

Rearranged during transfection (RET) kinase inhibitors

• Selpercatinib (Retevmo)
• Pralsetinib (Gavreto)

Anti-angiogenesis medications

Anti-angiogenesis medications inhibit cancer growth by preventing new blood vessel formation, known as angiogenesis, in the tumor microenvironment. Anti-angiogenesis medications include:

• Bevacizumab (Avastin, Mvasi), approved in combination with chemotherapy drugs cisplatin and paclitaxel.
• Ramucirumab (Cyramza), approved in combination with chemotherapy drug docetaxel and targeted therapy drug erlotinib.

Immunotherapy

Immunotherapy medications for NSCLC are monoclonal antibodies which work by stimulating the immune system to fight against cancer cells. T-cells are immune cells that normally induce programmed death in damaged or mutated cells. Immunotherapy boosts T-cell activity by blocking certain protein interactions and cell-signaling which prevent T-cells from attacking cancer cells. 

PD-1/PD-L1 inhibitors

PD-1/PD-L1 inhibitors enhance T-cell activity by blocking the interaction between protein molecules known as PD-1 and PD-L1 in T-cells. T-cell immune activation is inhibited when PD-1 and PD-L1 on the T-cell interact. Cancer cells escape programmed death by secreting PD-L1 or inducing the T-cells in the tumor microenvironment to produce PD-L1. 

PD-1/PD-L1 inhibitors approved by FDA for NSCLC are:

• Nivolumab (Opdivo)
• Pembrolizumab (Keytruda)
• Atezolizumab (Tecentriq)
• Durvalumab (Imfinzi)

CTLA-4 inhibitors

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors block the CTLA-4, a protein on T-cells which inhibits the T-cell’s immune response. The FDA-approved CTLA-4 in combination with nivolumab is:

• Ipilimumab (Yervoy)

Antiemetics and corticosteroids are almost always prescribed with chemotherapy medications to prevent nausea, vomiting and other side effects. FDA-approved medications for chemotherapy side effects include:

Antiemetics

• Ondansetron hydrochloride (Zofran)
• Granisetron (Sancuso, Sustol)
• Palonosetron hydrochloride (Aloxi)

Corticosteroids

• Prednisone
• Methylprednisolone
• Dexamethasone

• Please visit our medication section of each drug within its class for more detailed information.
• If your prescription medication isn’t on this list, remember to look on MedicineNet.com drug information or discuss with your healthcare provider and pharmacist.
• It is important to discuss all the drugs you take with your doctor and understand their effects, possible side effects and interaction with each other.
• Never stop taking your medication and never change your dose or frequency without consulting with your doctor.