Non-Small Cell Lung Cancer

Description

Alternative Names

Chemotherapy Treatments

Chemotherapy employs drugs given orally or by injection to destroy cancer cells that may have gone beyond the tumor. Until recently there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens and when supportive care was employed.

• Chemotherapy in Early Stages. Chemotherapy is proving to be beneficial in many patients as an additional treatment with surgery or radiation.
• Chemotherapy in Advanced Disease. Chemotherapy may be used as first-line therapy in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival.

Chemotherapy Drugs and Regimens

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin with gemcitabine, docetaxol, or vinblastine or a derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them, however. For elderly patients who cannot tolerate platinum compounds, gemcitabine and vinorelbine combination therapy may play a role.

Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic agents may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies.

Administration, Timing, and Drug Sequences

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than does early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer which may cure, shrink or keep the cancer from spreading.

Side Effects

Side effects of any chemotherapeutic regimen are common, are more severe with higher doses, and increase over the course of treatment, though some trials suggest that toxicities can be reduced by administering the drugs for shorter durations without loss of cancer-killing effects. Common side effects include the following:

• Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs. In one study, a combination of dexamethasone (a steroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting.
• Diarrhea.
• Temporary hair loss.
• Weight loss.
• Fatigue.
• Anemia. Anemia is common in lung cancer. It can be treated with transfusions or with injections of erythropoietin, an agent that stimulates red blood cell production. Erythropoetin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.
• Depression.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps one or two days per month.

Serious complications can also occur and may vary depending on the specific agents used. They include the following:

• Increased chance for infection from suppression of the immune system.
• Severe drops in white blood cells (neutropenia). Certain agents, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a type of drug called granulocyte colony-stimulating factor (either filgrastim and lenograstim).
• Liver and kidney damage. Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy with or without chemotherapy.
• Abnormal blood clotting (thrombocytopenia).
• Allergic reaction, particularly to platinum-based agents. (A simple skin test is under investigation that may identify people with a potential allergic response.)

Second-Line Chemotherapy

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that longer survival rates for advanced lung cancer being observed for the past five years may be due to these agents. Because platinum-based agents are most often used initially in most cases, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel (Taxotere) is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes higher toxicity than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the three-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed (Alimta), known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in cancer cell proliferation. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel (when docetaxel is given every 21 days but not weekly).

Gefitinib (Alessa) and Other Tyrosine Kinase Inhibitors. Much research is focusing drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). The spread of new blood vessels is controlled by compounds called growth factors, which may be important in cancer cell proliferation. Researchers, then, are interested in agents that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's life blood.

Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. They are the most studied to date and are both showing promise as second-line therapies.

• Gefitinib (Iressa) has now been approved as second-line therapy for non-small cell lung cancer. Many patients report significantly improvement in symptoms and quality of life. In one study, Iressa reduced tumor size by 50% in about 10% of the patients. Women may have a better response to the drug than men do. Iressa has been well tolerated. The most common side effects are mild to moderate diarrhea, nausea, skin rashes and acne, and weakness. Most are temporary. Experts hoped this drug would improve outcome as first-line therapy. But studies using it in combination with platinum-based chemotherapy have reported no advantages compared to chemotherapy alone except possibly in selected patients.
• Erlotinib (Tarceva) is also showing promise and may helpful in second-line therapies. It has very low toxicity (rash and diarrhea are common) and is currently being evaluated as first-line treatment.

As first line-line agents they be helpful only for specific patients, such as those who never smoked and patients with bronchoalveolar carcinoma (BAC). (This form of adenocarcinoma has a slow growth rate and is more likely to occur in nonsmokers.)

Combinations of Chemotherapy with Surgery, Radiation, or Both

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiotherapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any benefits in survival in patients with in advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to prolong the time to recurrence, overall survival duration, or both compared to radiation alone. Evidence is further suggesting that giving radiation concurrent with chemotherapy improves five-year survival rates compared to a sequential approach. Concurrent treatment is more toxic.

Other approaches use even more intensive multi-modal therapy. For example, some trials employ radiotherapy concurrent with chemotherapy followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Toxicities are high, however, with a combination of radiation and chemotherapy. Severe inflammation in the esophagus is the most common severe side effect of this regimen. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus, and long-term antibiotic therapy may be needed. Of note, although patients over 70 may suffer more from toxic effects than younger patients, a 2003 study suggested that they can achieve survival rates with combined treatments that are equal to those in younger patients.

Agents Used for Pain Relief

There are many painkilling medications available. Research has demonstrated that aggressive pain relief can help patients better manage cancer treatment symptoms other than pain. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and other symptoms as well.

Opioids are the most potent pain killers. Proper use of these strong medications is very important for achieving acceptable pain relief and preventing a toxic response. For instance, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a lethal overdose.

Drugs known as bisphosphonates, particularly zoledronic acid (Zometa), are proving to be useful in preventing complications from cancers that have metastasized to bones. The drug, in fact, may help reduce metastasis to the bone.