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Chemotherapy

The chart below lists the most commonly used chemotherapeutic agents for the treatment of lung cancer.

Standard chemotherapy for lung cancer typically consists of combinations of two or more of these drugs. Such combination therapy has been shown to improve the overall response to treatment. Well-known drug pairings in combination therapy include:

• paclitaxel plus carboplatin
• cisplatin plus vinorelbine tartrate
• cisplatin plus VP-16, and
• carboplatin plus VP-16.

Concurrent radiotherapy is very often used with the combinations of cisplatin plus VP-16 or carboplatin plus VP-16. In addition, researchers are now studying the effects of radiotherapy with the combination of paclitaxel plus carboplatin.

Other chemotherapeutic agents that may be used to treat lung cancer during clinical trials or alternative programs are:

Note: not all mentioned chemotherapeutic agents are approved by the Food and Drug Administration (FDA) for the treatment of lung cancer.

Anemia (low number of red blood cells) is a frequent side effect of chemotherapy and may cause symptoms such as extreme tiredness, dizziness, or shortness of breath. Epoetin alfa (Procrit®, Epogen®)—a synthetic hormone that stimulates red blood cell production—is a prescription drug available for the treatment of chemotherapy-related anemia.

Non-Small Cell Lung Carcinoma
Gemcitabine hydrochloride (Gemzar®) is a chemotherapeutic drug that has unique activity against many solid tumors, including non-small cell lung cancer (NSCLC). Combination therapy with gemcitabine, cisplatin (Platinol®), and vinorelbine tartrate (Navelbine®) has been found to be safe and very active in persons with advanced non-small cell lung cancer (NSCLC). Tumors in such individuals often cannot be removed by surgery (are unresectable), and so the patient may not survive for even one year without therapy.

The toxic side effects of combination chemotherapy are manageable in most patients. They include neutropenia (reduced number of granular white blood cells) and thrombocytopenia (reduced number of blood-clotting platelets).

Another treatment option for NSCLC patients with advanced disease is alternating chemo-radiotherapy (e.g., cisplatin and etoposide, followed by radiotherapy):

The toxic side effects of this program are leukopenia (reduced number of white blood cells) and vomiting.

Chemotherapeutic programs alone have limited activity against non-small cell lung cancer; however, new "protective" drugs, cytotoxic (cell-killing) agents, and radiotherapy techniques—either alone or in combination—are promising.

For example, the cell-protecting compound amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) is being tested for its defense of normal tissue against the toxic effects of chemotherapy and radiotherapy. This, or similar medication(s), may permit physicians to use higher doses of chemotherapeutic agents (e.g., cisplatin, carboplatin, paclitaxel), thereby improving therapeutic results, prognosis, and survival.

Small Cell Lung Carcinoma (Limited-Stage)
The following are standard treatment programs for limited-stage small cell lung cancer (SCLC). Combination chemotherapy—with or without prophylactic cranial (head) irradiation, or "PCI," for patients who respond completely—may be especially beneficial for those with impaired lung function or poor performance status. Individuals should be aware that PCI treatment may produce a condition known as leukoencephalopathy or leukodystrophy (degeneration of the brain tissue).

Leukoencephalopathy, which appears, on average, roughly 1 year after irradiation, can cause intellectual changes, memory alterations, and motor (movement) abnormalities.

A number of recent clinical trials have examined the treatment of small cell lung cancer. Of late, some of the most interesting approaches are treatments with biological agents such as monoclonal antibodies (immune system molecules) that are used alone or attached to a toxin; new chemotherapeutic agents; new radiation therapy schedules; new radiation techniques (e.g., three-dimensional treatment planning); and improved timing of chest radiation. Preliminary findings suggest that biological agents, in particular, may be active against SCLC; however, additional time and testing are required.

Small Cell Lung Carcinoma (Extensive-Stage)
A standard treatment method for patients with extensive-stage SCLC is combination chemotherapy, with or without prophylactic cranial irradiation (PCI), for individuals who respond entirely to such therapy. Some commonplace options—which produce similar survival rates—are:

Instead of these options, some physicians only use etoposide (VP-16, VePesid®) for chemotherapy in extensive-stage patients. Other less common combination chemotherapy programs include:

• Radiotherapy (radiation therapy) also may be delivered to metastatic areas that are not immediately destroyed by combination treatment. In particular, radiation may be directed at cancer metastases in the brain, spinal column, and bones.

In contrast to people who have never received chemotherapy, patients with prior chemotherapeutic histories often do not respond as well to additional chemotherapy. Yet such individuals—if medically stable—may be prescribed new agents that are available in clinical trials. Paclitaxel (Taxol®) and topotecan hydrochloride (Hycamtin®) are drugs that are undergoing further evaluation in such studies. Clinical trials normally provide for a change to standard combination therapy if the patient does not show a quick response to treatment.

In October 2007, the FDA approved Hycamtin® capsules for patients with relapsed small cell lung carcinoma following chemotherapy. Side effects of this drug, which is used at least 45 days after the end of first-line chemotherapy, include bone marrow suppression (neutropenia, throbocytopenia, anemia), nausea, and diarrhea.

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