title: Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B.
abstract: OBJECTIVE
  The Cancer and Leukemia Group B conducted a phase II study of gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously untreated malignant mesothelioma.
  
  
  METHODS
  Eligible patients had unresectable pleural or peritoneal mesothelioma, measurable disease, no prior therapy, and performance status 0-1 by Cancer and Leukemia Group B criteria. Gefitinib (500 mg p.o.) was administered once a day for 21 days. Patients underwent restaging after every two cycles. Therapy was continued until disease progression or unacceptable toxicity.
  
  
  RESULTS
  The most common grade 3 toxicities were diarrhea (16%) and nausea (12%). Of 43 patients enrolled, 1 patient (2%) had a complete response, 1 patient (2%) had a partial response, 21 (49%) had stable disease lasting two to eight cycles, 15 (35%) had progressive disease, and 5 (12%) had early deaths. One-year survival was 32% [95% confidence interval (CI), 21-50%]. Median survival and failure-free survival were 6.8% (95% CI, 3.5-10.3) and 2.6 months (95% CI, 1.5-4.0), respectively. The 3-month failure-free survival was 40% (95% CI, 25-56%). EGFR expression score by immunohistochemistry done in 28 patients was categorized as low (EGFR 1+ or 2+) or high (EGFR 3+) expression: 97% had EGFR overexpression (2+ or 3+). The median and 3-month failure-free survival were 3.6 months and 40% for those patients with low EGFR expression compared with 8.1 and 40% for those with high EGFR expression.
  
  
  CONCLUSIONS
  Although 97% of patients with mesothelioma had EGFR overexpression, gefitinib was not active in malignant mesothelioma. EGFR expression does not correlate with failure-free survival.
authors.affiliation: Department of Medicine, Washington University School of Medicine, 4960 Children's Place, Suite 108, St. Louis, MO 63110, USA. rgovinda@im.wustl.edu
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Niehans
authors.forename: Robin
authors.initials: R
authors.lastname: Vollmer
authors.forename: Dorothy
authors.initials: D
authors.lastname: Watson
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Kindler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib