title: Clinically meaningful improvement in symptoms and quality of life for patients with non-small-cell lung cancer receiving gefitinib in a randomized controlled trial.
abstract: PURPOSE Evaluation of disease-related symptom improvement rate by the Lung Cancer Subscale (LCS) of the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire was a coprimary end point of the pivotal phase II trial of gefitinib (Iressa; AstraZeneca, Wilmington, DE) conducted in the United States. This report includes the results of analyses exploring the relationship between weekly LCS scores and radiographic response and survival, as well as detailed protocol-specified analysis of symptom and quality-of-life data. PATIENTS AND METHODS In this trial, 216 symptomatic patients with advanced non-small-cell lung cancer (NSCLC) who had at least two prior chemotherapy regimens received gefitinib 250 or 500 mg/d. Disease-related symptoms were assessed weekly and quality of life was assessed monthly by LCS and FACT-L, respectively. Results Symptom improvement was rapid and correlated with tumor response and survival. At the recommended gefitinib dose of 250 mg/d, median overall survival times were 13.6 and 4.6 months for patients with and without symptom improvement, respectively, and 9.7 months for patients with symptom improvement without tumor response. Among patients with stable disease or disease progression, those with symptom improvement had significantly better overall survival than those without improvement. At 250 mg/d, 30% of patients showed a quality-of-life improvement that was correlated with tumor response. CONCLUSION This triadic analysis of response, survival, and symptom data supports the hypothesis that tumor response and symptom response are related and that each predicts survival. Among these NSCLC patients treated with gefitinib, symptom improvement was complementary to and, for most patients, preceded evidence of radiographic regression.
authors.affiliation: Evanston Northwestern Healthcare and Northwestern University, 1001 University Place, Ste 100, Evanston, IL 60201, USA. d-cella@northwestern.edu
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: Diane
authors.initials: D
authors.lastname: Prager
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: Anne
authors.initials: A
authors.lastname: Heyes
authors.forename: Judith S
authors.initials: JS
authors.lastname: Ochs
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wolf
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Kay
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Natale
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D000077156:Gefitinib; D006304:Health Status; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib