title: A phase II study of pemetrexed plus carboplatin followed by maintenance pemetrexed as first-line chemotherapy for elderly patients with advanced non-squamous non-small cell lung cancer.
abstract: A phase I study recommended carboplatin (CBDCA, area under the curve = 5) plus pemetrexed (PEM, 500 mg/m(2)) for elderly patients (≥75-years old) with non-squamous non-small cell lung cancer (NSCLC). PEM maintenance therapy was well tolerated. We conducted a multicenter phase II trial to evaluate the efficacy and safety of this regimen in elderly patients with NSCLC. Four courses of CBDCA plus PEM, followed by PEM, were administered. The primary endpoint was the 1-year overall survival (OS) rate, and the secondary endpoints were OS, progression-free survival (PFS), response rate (RR), and safety. Thirty-four patients (median age, 77 years) were enrolled between June 2012 and May 2013. The median observation time was 22.7 months. The primary endpoint of the 1-year OS rate was 58.0 % (95 % confidence interval (CI) 42.9-78.4 %), and RR and disease control rate were 41.2 and 85.3 %, respectively. Fourteen patients had partial responses, 15 had stable disease, 4 had disease progression, and 1 was not evaluated. The maintenance therapy rate was 58.8 %. The median PFS was 5.7 months (95 % CI 3.9-8.9 months), and median OS was 20.5 months (95 % CI 10.0-infinity months). Grade ≥3 hematological adverse events included leucopenia (23.5 % of patients), neutropenia (55.9 %), anemia (35.3 %), and thrombocytopenia (20.6 %). Grade ≥3 non-hematological adverse events included febrile neutropenia (8.8 %), elevated aminotransferases (5.9 %), infection (23.5 %), and anorexia/fatigue (5.9 %). Four patients had interstitial lung diseases (ILD) and one died due to ILD. CBDCA plus PEM, followed by PEM, was effective and reasonably tolerated in chemotherapy-naïve elderly patients with non-squamous NSCLC. Clinical Trial Registration This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (Trial Number UMIN 000004810).
authors.affiliation: Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tamiya
authors.affiliation: Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nakgasone-cho, Kita-ku, Sakai City, Osaka, 591-8555, Japan. atamiya@kch.hosp.go.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamiya
authors.affiliation: Faculty of Medicine, Kinki University, Osaka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Faculty of Medicine, Kinki University, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yoh
authors.affiliation: National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.affiliation: Yokohama Municipal Citizen's Hospital, Kanagawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Yokohama Municipal Citizen's Hospital, Kanagawa, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Shimokawa
authors.affiliation: Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Osaka City General Hospital, Osaka, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Daga
authors.affiliation: Osaka City General Hospital, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirashima
authors.affiliation: Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nakgasone-cho, Kita-ku, Sakai City, Osaka, 591-8555, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Atagi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D000068437:Pemetrexed / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000068437:Pemetrexed; D016190:Carboplatin
keywords: Carboplatin; Elderly; Maintenance; Non-small cell lung cancer; Non-squamous; Pemetrexed