title: Intercalated Dosing Schedule of Erlotinib and Docetaxel as a Therapeutic Strategy to Avoid Antagonism and Optimize Its Benefits in Advanced Non-Small-Cell Lung Cancer. A Randomized Phase II Clinical Trial.
abstract: BACKGROUND
  The purpose of this study was to assess whether an intercalated dosing schedule of erlotinib and docetaxel could avoid possible negative interactions and optimize the benefit obtained as second-line therapy in non-small-cell lung cancer (NSCLC) patients.
  
  
  METHODS
  A phase II randomized clinical trial was designed for advanced NSCLC patients in whom previous chemotherapy treatment had failed. The experimental arm with 33 patients consisted of erlotinib 150 mg/d orally, intermittent administration on days 2 to 16 every 21 days, combined with docetaxel 75 mg/m(2) every 21 days; the control arm with 35 patients consisted of erlotinib 150 mg/d orally, administered continuously. The study's primary end point was the proportion of patients who remained progression-free at 6 months in the 2 arms.
  
  
  RESULTS
  The proportion of patients who remained progression-free at 6 months was of 5 patients (15%) in the intercalated arm and 3 patients (9%) in the erlotinib monotherapy arm respectively. Median progression-free survival (PFS) was 3.0 versus 2.1 months (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.39-1.06; P = .086). Median overall survival (OS) was 7.5 and 5.2 months (HR, 0.70; 95% CI, 0.41-1.19; P = .19). Disease control rates were 51.7% and 36.4%, respectively. No new safety signals were observed.
  
  
  CONCLUSIONS
  Erlotinib and docetaxel with intermittent administration of erlotinib improved PFS, OS, and disease control rates compared with erlotinib alone. All of our results indicated that an intercalated dosing schedule of erlotinib and docetaxel could be more efficient than erlotinib treatment alone. Therefore, further studies should be developed in a larger number of patients. This study has shown the absence of antagonism between docetaxel and erlotinib when given in an intercalated fashion.
authors.affiliation: Hospital Universitari i Politècnic La Fe, Medical Oncology Department, Valencia, Spain. Electronic address: juan_osc@gva.es.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Juan
authors.affiliation: Hospital Virgen de los Lirios, Medical Oncology Department, Alcoy, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Aparisi
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Medical Oncology Department, Castellón, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Sánchez-Hernández
authors.affiliation: Hospital Universitario Dr Peset, Medical Oncology Department, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Muñoz-Langa
authors.affiliation: ITIC-Clínica Benidorm, Benidorm, Alicante, Spain.
authors.forename: Gaspar
authors.initials: G
authors.lastname: Esquerdo
authors.affiliation: Hospital Arnau de Vilanova, Medical Oncology Department, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: García-Sánchez
authors.affiliation: Hospital Universitari Sant Joan de Alicante, Medical Oncology Department, Alicante, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.affiliation: Hospital Arnau de Vilanova, Medical Oncology Department, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Garde
authors.affiliation: Hospital de Sagunto, Medical Oncology Department, Sagunto, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Giner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride
keywords: Adverse effects; Antineoplastic Combined Chemotherapy; Carcinoma; Docetaxel; Erlotinib