title: Phase II study of oral vitamin B12 supplementation as an alternative to intramuscular injection for patients with non-small cell lung cancer undergoing pemetrexed therapy.
abstract: OBJECTIVE
  A vitamin B12 supplement is required in pemetrexed single agent therapy. Intramuscular administration is the method of choice; however, oral administration is simpler and easier and may be sufficiently effective. We conducted a Phase II study to evaluate the safety of oral administration of vitamin B12 in patients with advanced non-small cell lung cancer who received pemetrexed single agent therapy.
  
  
  METHODS
  Folic acid and vitamin B12 were given orally for ˃ 1 week before pemetrexed administration. The primary end-point was onset of a grade ≥ 3 neutropenia ratio (50% of threshold expression ratios; an expectation expression ratio of 21%; α, 0.05; β, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180).
  
  
  RESULTS
  A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade ≥ 3 neutropenia was 36% (95% CI 22-52 %). Grade ≥ 3 non-hematologic toxicity and hematologic toxicity were seen in 20% (5 cases) and 44% (11 cases) of patients, respectively. In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2-3 cycle.
  
  
  CONCLUSIONS
  This study failed to meet its primary endpoint. We could not demonstrate the safety and efficacy of the 1-week vitamin B12 oral administration protocol as compared with intramuscular administration.
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.|MSD K.K., Tokyo, 1028667, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan. yhosomi@cick.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosomi
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagamata
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.
authors.forename: Kageaki
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.|Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, 2520375, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Nakahara
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Yomota
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.|National Cancer Center Hospital, Tokyo, 1040045, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Sunami
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuma
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.|Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, 2408555, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Shimokawa
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyoku, Tokyo, 1138677, Japan.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed / Q000009:adverse effects / Q000627:therapeutic use*; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000517:prevention & control; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000068437:Pemetrexed; D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Folic acid; Lung cancer; Pemetrexed; Vitamin