Mace, J.R., Keohan, M.L., Bernardy, H., Junge, K., Niebch, G., Romeis, P., . . . Baker, L.H. (2003). Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with high-dose ifosfamide. Clinical Cancer Research, 9, 5829–5834.

Study Purpose

To determine pharmacokinetics (PK) and efficacy of oral mesna

Intervention Characteristics/Basic Study Process

Patients were given IV mesna for the first dose and then randomized to IV or oral mesna for the following two doses. Crossover occurred at cycle two.

Sample Characteristics

  • N = 7 patients given ifosfamide 2g/m2/day for five days—16 evaluable for POB

Study Design

  • Phase I/II randomized crossover design of IV/oral mesna
  • Patients crossed over after first cycle
  • Study ran over two full cycles of chemotherapy

Measurement Instruments/Methods

  • Urine sampling and serum sampling for PK 
  • Weekly complete blood counts, serum chemistry, and urinalysis

Results

There were no significant differences in plasma PK between IV and oral. Rates of HC were not significant among IV and oral arms (3 of 16 for IV/IV/IV arm (90% CI 0.15 – 0.34) and 4 of 16 for IV/PO/PO arm (90% CI 0.23 – 0.52). Measurement of HC was not clearly defined.

Limitations

  • Small sample size
  • Crossover design gives more power and eliminates P-450 differences—power not addressed and so would decrease in LOE from I to II