Chemotherapy Treatments:

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

• Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
• Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin) and platinum-based chemotherapy is also a first-line treatment choice for patients with advanced, non-squamous cancer.

Chemotherapy Drugs and Regimens

Most chemotherapy regimens use platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin). The preferred regimen uses two drugs -- one of which is a platinum-based drug. Combinations may include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine (vindesine or vinorelbine). There do not seem to be any significant differences in effectiveness among these regimens. The gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds.

Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs 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. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer, is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic non-small cell lung cancer who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Administration, Timing, and Drug Sequences

Chemotherapy treatments are usually performed in an outpatient setting. They are given in regular cycles for several months. Researchers are still investigating how many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs. 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 the 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 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 that may cure, shrink, or keep the cancer from spreading.

Side Effects

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some studies suggest that side effects can be reduced by giving the drugs for shorter durations, without losing the cancer-killing effects.

Common side effects include the following:

• Diarrhea
• Temporary hair loss
• Weight loss
• Fatigue
• Depression
• Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate chemotherapy drugs, and in most patients who take more powerful drugs. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, significantly reduced or completely eliminated nausea and vomiting.
• Anemia: An abnormally low number of red blood cells is common in lung cancer. One treatment involves transfusions or injections of erythropoietin, a drug that increases red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These drugs improve patients' well-being and quality of life. Trials are in progress to determine whether they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with their normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur, and vary depending on the specific drugs. These complications include:

• Increased chance for infection from suppression of the immune system.
• Severe drop in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. A drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) can improve the white blood cell count.
• 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 come back after the first round of chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer in the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy.

Commonly used second-line agents include:

• Docetaxel (Taxotere). Docetaxel 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 more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if the weekly schedule achieves survival rates comparable to those of pemetrexed, however.
• Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new drug for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. 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 less toxic than docetaxel when docetaxel is given every 21 days, but not when it is given weekly.
• Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers are interested in medications 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 lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that non-small cell lung tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating non-small cell lung cancer in people who have never smoked.
  • Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trials have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
  • Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is taken by mouth and has very low risk of side effects (rash and diarrhea are common).

Combinations of Chemotherapy with Surgery, Radiation Therapy, or Both

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy after surgery in patients with lung cancers in stages Ib-IIIa. Some research indicates a 5% improvement in 5-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 tumors before surgery. Studies have been mixed as to whether there are any survival benefits in patients with 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 may delay a recurrence, extend survival time, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates. Chemotherapy and radiation treatments given at the same time are more toxic, however.

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

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest 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 shows that aggressive pain relief can help patients better manage cancer treatment symptoms. For example, one study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole. Chewing, inhaling, or injecting it can create a deadly overdose.