Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with high-dose ifosfamide.
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.
Mace
Joseph R
JR
Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0948, USA.
Keohan
Mary L
ML
Bernardy
Heinz
H
Junge
Klaus
K
Niebch
Georg
G
Romeis
Peter
P
Thoma
Aangelika
A
Wagner
Thomas
T
Mueller
Udo
U
Demetri
George
G
Baker
Laurence H
LH
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
D018906:Antineoplastic Agents, Alkylating; D020011:Protective Agents; D015080:Mesna; D007069:Ifosfamide