Pilot study assessing a seven-day continuous intrathecal topotecan infusion for recurrent or progressive leptomeningeal metastatic cancer

Abstract

Objective

To determine the feasibility and toxicity profile of topotecan administered as a seven-day continuous intrathecal infusion for patients with leptomeningeal metastasis secondary to recurrent or progressive central nervous system cancer.

Study design

Two patients with central nervous system leptomeningeal metastasis were treated with a seven-day continuous infusion of topotecan (0.2 mg/day) administered via continuous intrathecal/intraventricular infusion at a rate of 0.6 mL/h, totaling 1.4 mg/course. CSF and plasma concentrations of topotecan closed lactone (the active metabolite) were quantified at various points during topotecan infusion. Patients were monitored for neurologic and systemic toxicities according to NCI common toxicity criteria.

Results

Both patients tolerated the seven-day continuous topotecan without any significant adverse events. One patient received a second course 21 days after treatment initiation. CSF concentration of topotecan closed lactone ranged from 3.73 to 312 ng/mL (median = 131 ng/mL) and plasma topotecan closed lactone ranged from 0.44 to 1.78 ng/mL (median = 0.92 ng/mL). The median CSF topotecan concentration was greater than the median serum topotecan concentration by a 44-fold magnitude when samples were obtained at the same time point. None of the patients experienced any grade 3 or higher hematological toxicities or signs of arachnoiditis.

Conclusion

A seven-day continuous intrathecal infusion of topotecan is well tolerated and has the potential of maximizing central nervous system drug exposure.