title: Phase II Study of Carboplatin and Pemetrexed in Advanced EGFR-wild-type Non-squamous Non-small Cell Lung Cancer: The Central Japan Lung Study Group Trial 0906.
abstract: BACKGROUND
  Several pre-clinical and clinical studies suggest a potential predictive role of epidermal growth factor receptor (EGFR) mutation in responsiveness to cytotoxic chemotherapy. The aim of this phase II study was to evaluate the efficacy and safety of pemetrexed-carboplatin combination as first-line chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC) limited to EGFR-wild-type cases.
  
  
  METHODS
  In this single-arm, multicenter clinical trial, patients received pemetrexed (500 mg/m(2)) and carboplatin (area under the curve=6) intravenously on day 1 every 3 weeks for three to six cycles. The objective response rate (ORR) was the primary end-point; secondary end-points included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety.
  
  
  RESULTS
  A total of 54 patients were enrolled and 53 patients received therapy. No complete response was observed and partial response was observed in 19 (35.8%) cases, resulting in an ORR of 35.8% [95% confidence interval (CI)=23.1-50.2%]. Stable disease was observed in 20 (37.7%) patients and therefore the DCR was 73.6% (95% CI=59.7-84.7%). The median PFS was 5.4 months (95% CI=4.1-6.8 months) and the median OS was 12.7 months (95% CI=9.3-16.1 months). Treatment-related grade 3 or 4 hematological toxicities were neutropenia, leukopenia, anemia and thrombocytopenia in 35.8%, 11.3%, 30.2%, and 32.1% of patients, respectively. No grade 3 febrile neutropenia was observed, and grade 3 or 4 non-hematological toxicities were mild. There was no treatment-related death.
  
  
  CONCLUSIONS
  The pemetrexed-carboplatin combination was effective and well-tolerated in patients with EGFR-wild-type non-squamous NSCLC (UMIN-CTR number: UMIN000003393).
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi, Japan taniguchi@tosei.or.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Respiratory Medicine, Nagoya Medical Center, Nagoya, Aichi, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saka
authors.affiliation: Department of Respiratory Medicine, Nagoya Medical Center, Nagoya, Aichi, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kogure
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Aichi, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Shindo
authors.affiliation: Department of Respiratory Medicine, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ogasawara
authors.affiliation: Department of Respiratory Medicine, Komaki Municipal Hospital, Komaki, Aichi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kojima
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Respiratory Medicine, Nagoya Ekisaikai Hospital, Nagoya, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Respiratory Medicine, Toyohashi Municipal Hospital, Toyohashi, Aichi, Japan.
authors.forename: Ryujiro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Center for Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of Respiratory Medicine, Aichi Cancer Center Aichi Hospital, Okazaki, Aichi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed / Q000008:administration & dosage
chemical_list: D000068437:Pemetrexed; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Carboplatin; EGFR-wild-type; non-squamous non-small cell lung cancer; pemetrexed