title: Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with high-dose ifosfamide.
abstract: OBJECTIVE
  We conducted our study to determine the pharmacokinetics (PK) and clinical efficacy of oral mesna in patients receiving ifosfamide for soft tissue sarcoma.
  
  
  METHODS
  Seventeen patients were enrolled in a randomized prospective Phase I/II study. Seventeen patients were exposed to study medication. Ifosfamide was given at a dose of 2 g/m2/day for 5 days on a 21-day cycle. Before the first cycle, all patients were randomized onto a crossover design and received either the approved i.v. or i.v./oral mesna regimen, with crossover for the second cycle of chemotherapy. The i.v. mesna regimen consisted of dosings (20% ifosfamide dose) at 0, 4, and 8 h. The i.v./oral arm consisted of an i.v. mesna dosing (20% ifosfamide dose) at 0 h, followed by oral tablet dosing (40% ifosfamide dose) at 2 and 6 h. In-patient clinical monitoring and phlebotomy and urine sampling for mesna, dimesna, and ifosfamide PK were performed on all chemotherapy days.
  
  
  RESULTS
  Thirteen patients were evaluable for PK and 17 for efficacy and toxicity. No significant differences were detected in the plasma PK of the concomitantly infused ifosfamide. Rates of hemorrhagic cystitis were similar across mesna schedules. Four of 10 evaluable patients demonstrated objective response.
  
  
  CONCLUSIONS
  On the basis of our study, an i.v./oral mesna regimen is at least as uroprotective as the approved i.v. regimen. The i.v./oral regimen will improve patient tolerance and convenience, allow for a reduction in elective hospitalizations for ifosfamide chemotherapy, reduce the potential morbidity associated with inpatient administration of chemotherapy, and likely result in decreased costs of care.
authors.affiliation: Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0948, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Mace
authors.forename: Mary L
authors.initials: ML
authors.lastname: Keohan
authors.forename: Heinz
authors.initials: H
authors.lastname: Bernardy
authors.forename: Klaus
authors.initials: K
authors.lastname: Junge
authors.forename: Georg
authors.initials: G
authors.lastname: Niebch
authors.forename: Peter
authors.initials: P
authors.lastname: Romeis
authors.forename: Aangelika
authors.initials: A
authors.lastname: Thoma
authors.forename: Thomas
authors.initials: T
authors.lastname: Wagner
authors.forename: Udo
authors.initials: U
authors.lastname: Mueller
authors.forename: George
authors.initials: G
authors.lastname: Demetri
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D015080:Mesna / Q000493:pharmacokinetics*; D008875:Middle Aged; D011446:Prospective Studies; D020011:Protective Agents / Q000493:pharmacokinetics*; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D020011:Protective Agents; D015080:Mesna; D007069:Ifosfamide