Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with high-dose ifosfamide.

Abstract

PURPOSE:

We conducted our study to determine the pharmacokinetics (PK) and clinical efficacy of oral mesna in patients receiving ifosfamide for soft tissue sarcoma.

EXPERIMENTAL DESIGN:

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.

CONCLUSION:

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: Joseph R Mace, Mary L Keohan, Heinz Bernardy, Klaus Junge, Georg Niebch, Peter Romeis, Aangelika Thoma, Thomas Wagner, Udo Mueller, George Demetri, Laurence H Baker
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 16 Pt 1 Pg. 5829-34 (Dec 01 2003) ISSN: 1078-0432 [Print] United States
• PMID: 14676103 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Protective Agents
• Mesna
• Ifosfamide

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Agents, Alkylating (therapeutic use)
• Cross-Over Studies
• Female
• Humans
• Ifosfamide (therapeutic use)
• Infusions, Intravenous
• Male
• Mesna (pharmacokinetics)
• Middle Aged
• Prospective Studies
• Protective Agents (pharmacokinetics)
• Sarcoma (drug therapy, pathology)
• Soft Tissue Neoplasms (drug therapy, pathology)
• Treatment Outcome