title: Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged ≥ 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study).
abstract: We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported.
  
  
  
  The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety.
  
  
  
  Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients.
  
  
  
  UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. Electronic address: tnishina@shikoku-cc.go.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Moriwaki
authors.affiliation: Department of Surgery, Tokushima University, Tokushima, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Surgery, Tokushima University, Tokushima, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Higashijima
authors.affiliation: Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Tuchiura, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Tuchiura, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Masuishi
authors.affiliation: Division of Gastroenterology, Ibaraki Prefectural Central Hospital and Cancer Center, Kasama, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ozeki
authors.affiliation: Division of Gastroenterology, Ibaraki Prefectural Central Hospital and Cancer Center, Kasama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Amagai
authors.affiliation: Division of Gastroenterology, Kochi Health Sciences Center, Kochi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Negoro
authors.affiliation: Division of Surgery, Social Insurance Ritsurin Hospital, Takamatsu, Japan.
authors.forename: Shunju
authors.initials: S
authors.lastname: Indo
authors.affiliation: Division of Gastroenterology, Chiba Cancer Center, Chiba City, Japan.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
authors.affiliation: Department of Gastroenterology, Ryugasaki Saiseikai Hospital, Ryugasaki, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Sato
authors.affiliation: Division of Gastrointestinal Surgery and Surgical Oncology, Department of Surgery, Ehime University Graduate School of Medicine, Toon, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Nakajima
authors.affiliation: Department of Surgery, Mitoyo General Hospital, Kannonji, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Mizuta
authors.affiliation: Department of Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Takahashi
authors.affiliation: Division of Gastroenterology, Hitachinaka General Hospital, Hitachinaka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Department of Gastroenterology, National Hospital Organization Mito Medical Center, Ibarakicho, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Division of Surgery, Social Insurance Ritsurin Hospital, Takamatsu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maeba
authors.affiliation: Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D005641:Tegafur; D000068258:Bevacizumab; D014498:Uracil; D002955:Leucovorin
keywords: Chemotherapy; Clinical trial; First-line; Older; UFT