title: A prospective study of shortened vitamin supplementation prior to cisplatin-pemetrexed therapy for non-small cell lung cancer.
abstract: BACKGROUND
  Prior supplementation with folic acid and vitamin B12 is required to reduce pemetrexed therapy toxicity; the recommended lead-in time is at least 7 days. On the basis of previous pharmacokinetic and clinical studies, we hypothesized that the lead-in time could be shortened to 24 hours, enabling earlier commencement of standard chemotherapy; thus, we planned the first prospective trial of this regimen.
  
  
  METHODS
  Patients with advanced nonsquamous non-small cell lung cancer who had not previously received cytotoxic chemotherapy were enrolled. After measurement of homocysteine concentrations, the patients received 1,000 μg of vitamin B12 by intramuscular injection and began taking 350-500 μg of oral folic acid daily. Starting 24-48 hours after the vitamin B12 injection, the patients received intravenous 500 mg/m(2) pemetrexed and 75 mg/m(2) cisplatin for 4 cycles at 3 weekly intervals. The primary endpoint was the proportion of patients who developed neutropenia grade ≥3.
  
  
  RESULTS
  Thirty patients received chemotherapy starting within 48 hours of the vitamin B12 injection. No treatment-related deaths or grade 4 toxicity occurred. Neutropenia grade ≥3, other laboratory toxicities grade ≥3, and nonlaboratory toxicities grade ≥3 occurred in 6.7%, 13%, and 13% of patients, respectively. The baseline homocysteine concentrations were not higher in patients with grade ≥3 toxicities than in the remainder of the cohort (mean values, 8.6 and 10.7 μmol/L, respectively). The response rate to chemotherapy was 43%.
  
  
  CONCLUSIONS
  The shortened vitamin supplementation was well tolerated and retained antitumor efficacy. Analysis of baseline homocysteine concentrations confirmed the efficacy of short-term vitamin supplementation.
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan ytakagi-tmd@umin.net.
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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, 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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, 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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, 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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, 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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, 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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, 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, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Iguchi
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibuya
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D011446:Prospective Studies; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D005492:Folic Acid; D014805:Vitamin B 12; D002945:Cisplatin
keywords: Chemotherapy; Homocysteine; Non-small cell lung cancer; Pemetrexed; Vitamin supplementation