The study, presented at the 38th annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida, evaluated 216 patients with recurrent non-small-cell lung cancer who had undergone two or more rounds of chemotherapy. One group of patients received 250 mg of ZD 1839 (Iressa) daily, while the second group received ZD 1839 at 500 mg each day until the disease progressed. The investigators found that lung cancer symptoms, such as cough, shortness of breath, chest pain or tightness, appetite and fatigue, were greatly improved in about 40 percent of patients. Further, they found that symptom improvement was associated with a longer survival.
“Our results show that patients who felt better after taking ZD 1839, actually lived longer than those whose symptoms did not improve,” said Dr. Natale. “This is important because it shows that a daily pill reduced symptoms such to the extent that many of our patients were able to resume their normal activities and enjoy life for longer.”
ZD 1839 (Iressa), a pill developed by AstraZeneca, has been found to work in both laboratory and clinical trials by targeting and blocking a key growth signaling mechanism in cancer cells called the epidermal growth factor receptor (EGFR). Otherwise known as HER1, the EGFR is a part of the “HER kinase family” of proteins that control cell growth and can stimulate the spread of cancer when over-expressed on malignant cells.
Non-small-cell lung cancer is the most common type of lung cancer, a disease that kills about 155,000 Americans each year. Typically, non-small-cell lung cancer is treated with surgery and chemotherapy. But because it is usually diagnosed in its advanced stages, these treatments rarely bring about a cure, leading doctors to try to control their patients’ cancer with chemotherapy or radiation treatments. The side effects from these treatments, however, can often outweigh any survival benefit that patients might receive.
“The challenge for those of us treating patients with advanced lung cancer today, is how we can manage our patients care so that the side effects from these treatments aren’t worse than the symptoms,” commented Dr. Natale.
To find out whether ZD 1839 reduced the symptoms of patients with non-small-cell lung cancer, the investigators evaluated 216 patients whose disease had progressed after at least two prior rounds of chemotherapy. Among these patients, 102 were randomly selected to receive 250 mg of ZD 1839 each day, while 114 received a higher dose of the drug at 500 mg. Symptoms of the disease were monitored weekly using a specially developed seven-item questionnaire, in which patients rated the severity of their symptoms on a scale of 0 to 4. Quality of life was measured monthly using a similar self-administered questionnaire. Both questionnaires had been extensively tested and validated in previous lung cancer trials and had been shown to measure meaningful improvements in lung cancer symptoms and patient quality of life. Symptoms were considered to be reduced if the total score on the symptom scale improved by at least two points for greater than a month.
The investigators found that symptoms were significantly reduced in 43 percent of patients receiving the lower dose of ZD 1839, while 34 percent of those receiving the higher dose experienced fewer symptoms. Side effects were minimal and included mild skin reactions and diarrhea. They also found that quality of life was improved in 34 percent of patients who responded to the lower dose of ZD 1839 as compared to 23 percent of patients receiving ZD 1839 at 500 mg.
“Although patients at both dose levels tolerated ZD 1839 reasonably well, there were fewer and less severe side effects at the 250 mg dose compared to the 500 mg dose level,” said Dr. Natale. “Since there were no significant differences between dose levels in these patients’ quality of life or symptom improvement, the recommended dose will be 250 mg.”
In addition, the investigators found that about 11 percent of patients had significant tumor regression (objective response), as measured by CT scans, and another 30 percent had disease stabilization for at least two months. Interestingly, symptoms were improved in 95 percent of patients whose tumors shrank in response to treatment, while 71 percent with stable disease (lung cancer that had neither progressed or diminished in response to treatment) experienced fewer symptoms. Quality of life was also improved in 86 percent of the patients who responded to treatment and in 52 percent of patients with stable disease. Further, the investigators observed that patients with reduced symptoms lived almost five months longer than those whose symptoms did not improve.
“The truly surprising findings from this study were not only that patients with fewer symptoms lived longer, but that patients felt better and had fewer symptoms despite whether or not their tumors responded to treatment with ZD 1839,” said Dr. Natale. “This represents a significant step forward for patients battling this disease.”
Cedars-Sinai Medical Center is one of the largest non-profit academic medical centers in the Western United States. For the fifth straight two-year period, Cedars-Sinai has been named Southern California’s gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthrough in biomedical research and superlative medical education. Named one of the 100 “Most Wired” hospitals in health care in 2001, the Medical Center ranks among the top 10 non-university hospitals in the nation for its research activities.
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