title: Randomized phase II study of pulse erlotinib before or after carboplatin and paclitaxel in current or former smokers with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  A prior study demonstrated that addition of continuous daily erlotinib fails to improve response rate or survival in non-small-cell lung cancer (NSCLC) patients treated with carboplatin and paclitaxel. However, preclinical data support the hypothesis that intermittent administration of erlotinib before or after chemotherapy may improve efficacy. We tested this hypothesis in patients with advanced NSCLC.
  
  
  METHODS
  Eligible patients were former or current smokers with chemotherapy-naive stage IIIB or IV NSCLC. All patients received up to six cycles of carboplatin (area under the curve = 6) and paclitaxel (200 mg/m(2)), with random assignment to one of the following three erlotinib treatments: erlotinib 150 mg on days 1 and 2 with chemotherapy on day 3 (150 PRE); erlotinib 1,500 mg on days 1 and 2 with chemotherapy on day 3 (1,500 PRE); or chemotherapy on day 1 with erlotinib 1,500 mg on days 2 and 3 (1,500 POST). The primary end point was response rate.
  
  
  RESULTS
  Eighty-six patients received treatment. The response rates for the 150 PRE, 1,500 PRE, and 1,500 POST arms were 18% (five of 28 patients), 34% (10 of 29 patients), and 28% (eight of 29 patients), respectively. The median overall survival times were 10, 15, and 10 months for the 150 PRE, 1,500 PRE, and 1,500 POST arms, respectively. The most common grade 3 and 4 toxicities were neutropenia (39%), fatigue (15%), and anemia (12%). Grade 3 and 4 rash and diarrhea were uncommon.
  
  
  CONCLUSIONS
  Patients treated on the 1,500 PRE arm had the highest response rate and longest survival, with ranges similar to those reported for carboplatin, paclitaxel, and bevacizumab in a more restricted population. Further evaluation of this strategy in a phase III trial is proposed.
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10022, USA. rielyg@mskcc.org
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Milton
authors.forename: David B
authors.initials: DB
authors.lastname: Solit
authors.forename: Neal
authors.initials: N
authors.lastname: Rosen
authors.forename: Emir
authors.initials: E
authors.lastname: Senturk
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
authors.forename: Francis M
authors.initials: FM
authors.lastname: Sirotnak
authors.forename: Venkatraman E
authors.initials: VE
authors.lastname: Seshan
authors.forename: Margaret
authors.initials: M
authors.lastname: Fogle
authors.forename: Michelle
authors.initials: M
authors.lastname: Ginsberg
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D012907:Smoking; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D017239:Paclitaxel