title: A pilot study: sequential gemcitabine/cisplatin and icotinib as induction therapy for stage IIB to IIIA non-small-cell lung adenocarcinoma.
abstract: BACKGROUND
  A phase II clinical trial previously evaluated the sequential administration of erlotinib after chemotherapy for advanced non-small-cell lung cancer (NSCLC). This current pilot study assessed the feasibility of sequential induction therapy in patients with stage IIB to IIIA NSCLC adenocarcinoma.
  
  
  METHODS
  Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8 and cisplatin 75 mg/m(2) on day 1, followed by oral icotinib (125 mg, three times a day) on days 15 to 28. A repeat computed tomography(CT) scan evaluated the response to the induction treatment after two 4-week cycles and eligible patients underwent surgical resection. The primary objective was to assess the objective response rate (ORR), while EGFR and KRAS mutations and mRNA and protein expression levels of ERCC1 and RRM1 were analyzed in tumor tissues and blood samples.
  
  
  RESULTS
  Eleven patients, most with stage IIIA disease, completed preoperative treatment. Five patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ORR = 45%) and six patients underwent resection. Common toxicities included neutropenia, alanine transaminase (ALT) elevation, fatigue, dry skin, rash, nausea, alopecia and anorexia. No serious complications were recorded perioperatively. Three patients had exon 19 deletions and those with EGFR mutations were more likely to achieve a clinical response (P= 0.083). Furthermore, most cases who achieved a clinical response had low levels of ERCC1 expression and high levels of RRM1.
  
  
  CONCLUSIONS
  Two cycles of sequentially administered gemcitabine/cisplatin with icotinib as an induction treatment is a feasible and efficacious approach for stage IIB to IIIA NSCLC adenocarcinoma, which provides evidence for the further investigation of these chemotherapeutic and molecularly targeted therapies.
authors.affiliation: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Beijing, Haidian District 100142, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lv
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.forename: Qin
authors.initials: Q
authors.lastname: Feng
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Bingtian
authors.initials: B
authors.lastname: Zhao
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zheng
authors.forename: Shaolei
authors.initials: S
authors.lastname: Li
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Yuzhao
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Pei
authors.forename: Jian
authors.initials: J
authors.lastname: Fang
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D043844:Crown Ethers / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D043844:Crown Ethers; D004268:DNA-Binding Proteins; D011799:Quinazolines; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C531470:icotinib; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D000093542:Gemcitabine