The researchers studied symptom improvement in the Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL 2) trial, which included 216 symptomatic patients with locally advanced or metastatic NSCLC who had more than two prior chemotherapy regimens containing platinum and docetaxel(Drug information on docetaxel) (Taxotere) (given separately or concurrently). Patients received 250 or 500 mg/d of oral gefitinib(Drug information on gefitinib).
Disease-related symptoms were assessed weekly by the Lung Cancer Subscale (LCS) of the FACT-L questionnaire. The LCS includes seven items (cough, shortness of breath, tightness in chest, breathing difficulty, appetite loss, weight loss, and unclear thinking), and the maximum attainable (asymptomatic) score on the FACT-L is 28.
LCS response was defined as a 2 point or greater improvement in LCS score sustained for at least 4 weeks with no worsening at any interim weekly time point. "A group-average change in LCS score of 2 to 3 points was considered to be clinically meaningful and correlated with differences in weight loss, performance status, primary disease symptoms, best response to treatment, and time to disease progression," Dr. Cella said.
The median baseline LCS scores were 16.7 in the group receiving 250 mg/d gefitinib and 16 for patients receiving 500 mg/d.
Study Results
"The overall symptom improvement rate across both doses was 39%. Symptom improvement was rapid: The median time to symptom improvement was 9 to 10 days, and the median duration was more than 7 months in the 250 mg/d group and 5.4 months in the 500 mg/d group," Dr. Cella reported.
Similar symptom improvement rates were seen when the 2-point criterion for symptom improvement was increased to 3 points. "Even applying a 7-point criterion gave symptom improvement rates of 16.7% and 11.4% for patients receiving 250 mg/m2/d and 500 mg/m2/d, respectively," he said.
A correlation between symptom improvement and tumor response was observed at both gefitinib dose levels, such that most patients who had an objective tumor response or stable disease showed symptom improvement (P < .0001).
Among the patients who survived for more than 8 weeks, median overall survival was greater for those who had symptom improvement than for those who did not (11.8 months vs 4.9 months, respectively). Patients who had symptom improvement but did not have a partial response had median overall survival of 9.7 months. Patients with stable disease also had longer median overall survival if they had symptom improvement than if they did not.
"Because it forecasts partial response and overall survival, the symptom improvement seen with gefitinib is unlikely to be due to a placebo effect. Symptom improvement information is clinically meaningful and complementary to a direct antitumor effect in these heavily pretreated patients with advanced NSCLC," Dr. Cella concluded.
