Ventriculolumbar perfusion chemotherapy with methotrexate for treating leptomeningeal carcinomatosis: a Phase II...

The efficacy of ventriculolumbar perfusion (VLP) chemotherapy with methotrexate (MTX) was evaluated for treatment of leptomeningeal carcinomatosis (LMC).

The primary outcome was the response rate of increased intracranial pressure (ICP), which was available for comparison from historical data on conventional intraventricular chemotherapy. Secondary endpoints were response rates of other LMC symptoms and overall survival of patients. Artificial cerebrospinal fluid (CSF) premixed with MTX was continuously perfused intraventricularly through a preinstalled intraventricular reservoir and drained via lumbar catheter for 72 hours. The VLP was repeated twice at 3-day intervals for each cycle.

Forty-five of 65 patients had increased ICP, and 32 patients (71%) showed response after VLP chemotherapy, including 31 patients with normalization of ICP. Altered mentation improved in 7 of 21 patients (33%). Cauda equina symptoms responded in 5 of 27 patients (19%), including 4 patients who became ambulatory from a bedridden state. Median overall survival was 187 days, and the 1-year survival rate was 27%. All side effects, including nausea, vomiting, confusion, and sleep disturbance, were tolerable and transient except for two cases of CSF infection.

VLP chemotherapy with MTX provided better control of increased ICP, improved symptom response, and prolonged survival at a cost of acceptable toxicity in patients with LMC.