title: Phase II study of cetuximab, docetaxel, and gemcitabine in patients with previously untreated advanced non-small-cell lung cancer.
abstract: BACKGROUND
  Targeting epidermal growth factor receptors (EGFRs) has been a novel strategy in treating non-small-cell lung cancer (NSCLC). This multicenter, community-based trial was designed to examine the role of cetuximab in combination with a nonplatinum regimen.
  
  
  METHODS
  Eligibility criteria were newly diagnosed unresectable stage III/IV NSCLC, all histologies, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Treatment premedication included dexamethasone 20 mg orally 12 and 6 hours before treatment, and 4 mg 12 hours following treatment; diphenhydramine 50 mg intravenously (I.V.) and cimetidine 300 mg I.V. before cetuximab. Treatment medication included docetaxel 30 mg/m2 I.V. days 1 and 8; gemcitabine 1000 mg/m2 I.V. days 1 and 8; and cetuximab 400 mg/m2 I.V. day 1, then 250 mg/m2 I.V. weekly. Patients received up to 6 cycles with restaging every 6 weeks. The primary endpoint was an overall response rate (ORR) > or = 25%.
  
  
  RESULTS
  Sixty-nine patients enrolled from July 2005 to October 2007. Patients had a median age of 69 years; 70% were male and 30% were female; ECOG PS was 0 in 42%, 1 in 51%, and 2 in 7%; patients had adenocarcinoma (42%), squamous cell (30%), large cell (6%), mixed (1%), and not otherwise specified (20%) disease. The ORR was 17% (95% CI, 9%-29%). Thirty-five patients (54%) had stable disease; 14 patients (22%) had progressive disease. With a median follow-up of 17.8 months, the median progression-free and overall survivals were 4 months and 9.4 months, respectively. The most common (> 10%) grade 3/4 toxicities were neutropenia (25%), rash (22%), and fatigue (12%). Accrual in our middle Tennessee offices was temporarily suspended and ultimately stopped because of a higher-than-anticipated rate of cetuximab-related severe hypersensitivity reactions (HSRs) in 4 patients among the first 12 enrolled, including 1 fatal event.
  
  
  CONCLUSIONS
  Cetuximab/docetaxel/gemcitabine was relatively well-tolerated and associated with efficacy similar to chemotherapy alone. Additional study with cetuximab/chemotherapy in NSCLC should focus on new potentially predictive biomarkers. Also, additional study is needed to better understand and prevent the severe HSRs that appear to be endemic to specific regions of the United States.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA. dspigel@tnonc.com
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.forename: Charles
authors.initials: C
authors.lastname: Webb
authors.forename: James
authors.initials: J
authors.lastname: Rubinsak
authors.forename: Roger C
authors.initials: RC
authors.lastname: Inhorn
authors.forename: James
authors.initials: J
authors.lastname: Reeves
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Vazquez
authors.forename: Cassie M
authors.initials: CM
authors.lastname: Lane
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004342:Drug Hypersensitivity / Q000453:epidemiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D013714:Tennessee; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000068818:Cetuximab; D000093542:Gemcitabine