title: Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial.
abstract: OBJECTIVE
  We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing.
  
  
  RESULTS
  Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response.
  
  
  CONCLUSIONS
  The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.
authors: Division of Hematology/Oncology, University of Texas Health Science Center at San Antonio, Cancer Therapy and Research Center, 7979 Wurzbach Rd, MC8232, Zeller Building, 4th Floor, Room Z418, San Antonio, TX 78229, USA. Argiris@uthscsa.edu
authors: Athanassios
authors: A
authors: Argiris
authors: Musie
authors: M
authors: Ghebremichael
authors: Jill
authors: J
authors: Gilbert
authors: Ju-Whei
authors: JW
authors: Lee
authors: Kamakshi
authors: K
authors: Sachidanandam
authors: Jill M
authors: JM
authors: Kolesar
authors: Barbara
authors: B
authors: Burtness
authors: Arlene A
authors: AA
authors: Forastiere
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000235:genetics; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D000077156:Gefitinib; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D018631:ras Proteins
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000077156:Gefitinib