Separate, not together: chemotherapy followed by gefitinib offers survival benefit

This study examined the use of gefitinib (Iressa) following chemotherapy in patients with stage 3 epidermal-growth-factor receptor positive non-small cell lung cancer that has spread to nearby lymph nodes.

The initial treatment for non-small cell lung cancer is usually surgical removal of the tumor, which can result in cure for patients in the early stages of the disease. For patients with stage 3 cancer that has spread to nearby lymph nodes, surgery alone leads only to a 23% survival rate; therefore surgery is generally followed by chemotherapy.

Some patients also have a genetic mutation that increases the activity of the epidermal-growth-factor receptor, or EGFR. This receptor can increase tumor cell production and migration (the spread of tumor cells beyond the original tumor site). EGFR tyrosine-kinase inhibitors can block the activity of these receptors, decreasing tumor growth and spread.

Gefitinib (Iressa) is an EGFR tyrosine-kinase inhibitor that has been shown to be safe and effective as a first-line treatment for patients with EGFR-positive non-small cell lung cancer. However, when used simultaneously with chemotherapy, it did not increase overall survival times compared to chemotherapy alone. Therefore, the current study explored whether survival benefits increased when gefitinib was used following chemotherapy treatment with pemetrexed (Alimta) and carboplatin (Paraplatin).

In this study, 60 patients with stage 3 N2 (spread to nearby lymph nodes) EGFR mutation-positive cancer were randomly assigned to receive either chemotherapy alone or chemotherapy followed by gefitinib. All patients received four cycles of chemotherapy, after which half then received 250 mg of gefitinib daily for 6 months. Average follow-up time was 30.6 months. Disease-free survival (the time to recurrence), overall survival (the time to death from any cause), and adverse events (negative side effects) were measured.

Patients who received both chemotherapy and gefitinib had an average disease-free survival time of 39.8 months, compared to 27 months for chemotherapy alone. 78.9% of patients receiving both chemotherapy and gefitinib experienced at least 2 years of disease-free survival, compared to 54.2% of patients receiving only chemotherapy. While there was an increase in 2-year overall survival rates for patients receiving chemotherapy and gefitinib (92.4%) compared to chemotherapy alone (77.4%), this was not statistically significant.

The average survival time for patients receiving chemotherapy and gefitinib treatments was 41.6 months, compared to 32.6 months in patients receiving chemotherapy alone. 93.3% of patients receiving chemotherapy and gefitinib and 86.7% of those receiving chemotherapy alone experienced an adverse event. Gefitinib increased rates of mild or moderate skin rash and diarrhea.

This study concluded that gefitinib treatment following chemotherapy safely increased disease-free survival times in patients with stage 3-N2 epidermal-growth-factor receptor positive non-small cell lung cancer.