Adenocarcinoma of the lung medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shanshan Cen, M.D. [2]

Overview

The predominant therapy for adenocarcinoma of the lung is surgical resection. Adjunctive chemotherapy, radiation therapy, and target tharapy may be required.

Medical Therapy

Chemotherapy

• Chemotherapy is commonly used to treat non–small cell lung cancer (NSCLC).

• Chemotherapy is the use of anticancer (cytotoxic) drugs to treat cancer. It is usually a systemic therapy that circulates throughout the body and destroys cancer cells, including those that may have broken away from the primary tumor.

• Chemotherapy may be used:

• As primary treatment, with or without radiation therapy, to destroy cancer cells
• Before surgery, often with radiation therapy, to shrink a tumor (neoadjuvant chemotherapy) so that it may be completely removed (Surgery is done 3–5 weeks after chemotherapy).
• After surgery to destroy cancer cells left behind and to reduce the risk of the cancer recurring (adjuvant chemotherapy)
• To relieve pain or to control the symptoms of advanced non–small cell lung cancer (palliative chemotherapy)

Chemotherapy drugs

• Non–small cell lung cancer is usually treated with a combination of 2 drugs, which are more effective than any one drug alone. The addition of a third drug does not improve the effectiveness of the chemotherapy, but may cause more side effects. The combinations of drugs are given intravenously for 3–6 cycles. In some cases, they are given until the disease progresses.

• The most common chemotherapy drug combinations used for non–small cell lung cancer include cisplatin (Platinol AQ) (cisplatin-based therapy) as one of the drugs:

• Cisplatin and etoposide (Vepesid) (this combination is most often given with concurrent radiation therapy)
• Cisplatin and vinorelbine (Navelbine) (this combination may be given at the same time as radiation therapy, which is called concurrent therapy)
• Cisplatin and docetaxel (Taxotere)
• Cisplatin and gemcitabine (Gemzar)
• Cisplatin and pemetrexed (Alimta) (this combination is not used for squamous cell types of non–small cell lung cancer)

• If a person cannot take cisplatin, a related drug called carboplatin (Paraplatin, Paraplatin AQ) may be used with the above drugs.

• Single drugs may be used to treat a person with advanced or metastatic non–small cell lung cancer if they:

• Cannot have combination chemotherapy because of other medical conditions
• Have already had one chemotherapy combination that has stopped working

• The most common single drugs used for non–small cell lung cancer are:

• Gemcitabine
• Docetaxel
• Vinorelbine
• Pemetrexed

Targeted chemotherapy

• Targeted chemotherapy is a newer way to treat non–small cell lung cancer. Targeted therapy means the cancer treatment is aimed at a particular molecule (for example, proteins) in the cancer cells (the target).
• There are two types of targeted chemotherapy used for non–small cell lung cancer.

• EGFR inhibitors

• An epidermal growth factor receptor (EGFR) is a protein on cancer cells. It sends signals that promote growth and survival of cancer cells. EGFR inhibitors block these receptors, cutting off the signal pathway and causing the cancer cells to die.

• In a small number of non–small cell lung cancers (usually adenocarcinomas), a mutation develops in the EGFR gene that drives the growth of the cancer. These mutations, known as activating mutations, can be targeted by drugs known as EGFR tyrosine kinase inhibitors. EGFR tyrosine kinase inhibitors block these receptors, cutting off the signal pathway and causing the cancer cells to die.

• The types of EGFR tyrosine kinase inhibitors used for non–small cell lung cancer are:

• Gefitinib (Iressa) is used for locally advanced or metastatic EGFR-positive non–small cell lung cancer tumors.
• Afatinib (Giotrif) is used for metastatic EGFR-positive non–small cell lung cancer tumors that have not been previously treated with tyrosine kinase inhibitors.
• Erlotinib (Tarceva) is used as a third chemotherapy option for people with EGFR-positive tumors or tumors that have unknown EGFR status that have not responded to 2 other chemotherapy combinations. It is used as a second chemotherapy option for people who cannot have other chemotherapy drugs.

• ALK inhibitors

• The anaplastic lymphoma kinase (ALK) gene sends signals to protein molecules that make cells grow and divide.

• A small number of non–small cell lung cancers (usually adenocarcinomas) have a mutation in the ALK gene. These cancers are called ALK-positive. When a cancer is ALK-positive, ALK inhibitors can be used to treat it. ALK inhibitors block the signals that tell the cancer cells to divide, so the cancer stops growing.

• Only non–small cell lung cancers that test positive for the ALK gene are treated with ALK inhibitors. The following ALK inhibitors are for non–small cell lung cancer:

• Crizotinib (Xalkori) is used as the first drug to treat people with locally advanced or metastatic ALK-positive non–small cell lung cancer.
• Ceritinib (Zykadia) may be offered to people who have ALK-positive non–small cell lung cancer that has progressed while taking crizotinib.

Timing of chemotherapy

• Chemotherapy given at the same time as radiation therapy is called concurrent (or concomitant) therapy. Chemotherapy drugs used to treat non–small cell lung cancer can be given on some of the same days as radiation therapy treatments. Cisplatin, which is a standard drug used for non–small cell lung cancer, makes cancer cells more sensitive to the effects of radiation.

• Chemotherapy given before or after radiation therapy is called sequential therapy. With non–small cell lung cancer, chemotherapy is usually given before radiation therapy.

• Concurrent therapy may improve the effectiveness of both treatments, but it can also cause more side effects. Sequential treatment has fewer side effects, but it is less effective. The timing of chemotherapy and radiation therapy depends on the treatment setting and should be discussed with the oncologist.

Maintenance chemotherapy

• Maintenance therapy is given after the first-line therapy (the first or standard treatment) to keep a disease (such as cancer) under control or to prevent it from coming back (recurring).

• Maintenance chemotherapy may be offered to people with non–small cell lung cancer that has responded to chemotherapy. The drugs sometimes used as maintenance therapy are:

• Erlotinib is used for people with EGFR-positive tumors or tumors that have unknown EGFR status. However, it is rarely used in Canada.
• Pemetrexed is for maintenance therapy, but it is not used for squamous cell types of non–small cell lung cancer.

Radiation

• Radiation therapy uses high-energy rays or particles to destroy cancer cells. Radiation may be used for non–small cell lung cancer:

• As primary treatment, with chemotherapy, for tumors that cannot be removed by surgery
• Before surgery, usually with chemotherapy, to shrink a tumour (neoadjuvant radiation therapy)
• After surgery, usually with chemotherapy, if the tumor was not completely removed or if there were cancer cells in the surgical margins (positive margins)
• Alone as the primary treatment for people who cannot have surgery or chemotherapy
• To relieve pain or to control the symptoms of advanced non–small cell lung cancer (palliative radiation therapy)
• To treat a single brain metastasis

• People with stage I or II non–small cell lung cancer that can be completely removed by surgery are not offered radiation therapy after surgery (adjuvant radiation therapy) because it reduces survival.

• The amount of radiation given during treatment, and when and how it is given, will be different for each person.

External beam radiation therapy

• Non–small cell lung cancer is usually treated with external beam radiation therapy. A machine directs radiation to the tumor and some of the surrounding tissue. The most common form of external beam radiation therapy is 3-dimensional conformal radiation therapy (3-D CRT). During 3-D CRT, doctors use a CT scan to guide the radiation treatment to the tumor. This technique reduces the amount of radiation to surrounding tissues.
• Stereotactic radiation therapy

• Stereotactic radiation therapy is a type of external beam therapy. It may be used with non–small cell lung cancer to treat a single brain metastasis. It is also being used for early stage non–small cell lung cancer where surgery must be avoided due to other health concerns.

• Intensity-modulated radiation therapy (IMRT)

• Intensity-modulated radiation therapy (IMRT) delivers different doses of radiation to different areas. It uses a machine with special “leaves” that can shape the treatment area to target the tumor. It may be used to treat a non–small cell lung tumor that is close to the spinal cord. Further research is needed to clarify the role of IMRT in the treatment of non–small cell lung cancer.

Brachytherapy

• Brachytherapy is internal radiation therapy. A radioactive material (radioactive isotope) is placed right into, or very close to, the tumor. Radioactive materials can also be placed in the area from where the tumor was removed. The radiation kills the cancer cells over time.

• Brachytherapy may be used to treat a non–small cell lung cancer tumor that is blocking the large airways of the lung. The doctor places the radioactive isotope into the airways during bronchoscopy (endobronchial radiation therapy). In rare situations, brachytherapy may be used as a primary treatment for people who cannot have external beam radiation therapy because of poor lung function.

Timing of radiation therapy

• Radiation therapy given at the same time as chemotherapy is called concurrent (or concomitant) therapy. Chemotherapy used to treat non–small cell lung cancer may be given on some of the same days as radiation therapy treatments. Cisplatin (Platinol AQ), which is a standard drug used for non–small cell lung cancer, makes cancer cells more sensitive to the effects of radiation.

• Radiation therapy given before or after chemotherapy is called sequential therapy. With non–small cell lung cancer, chemotherapy is usually given before radiation therapy.

• Concurrent therapy may improve the effectiveness of both treatments, but it can also cause severe side effects. Sequential treatment has fewer side effects.

References

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