Twenty-three adult patients with meningeal involvement by a variety of malignancies were treated with the intra-Ommaya combination of methotrexate, hydrocortisone, cytosine arabinoside, and thio-TEPA. Whole brain irradiation was also administered to most patients who had not previously received it. Most patients demonstrated improvement of cerebrospinal fluid parameters, but only 50% of the patients experienced neurological improvement. Patients who did not receive cranial irradiation and performance status 4 patients were less likely to respond than were patients who did receive cranial irradiation as part of their treatment and patients who were performance status 0-3. Four patients developed possible and 2 patients developed probable or definite serious neurological complications. Another 4 patients developed less severe, reversible neurological toxicity. It is possible (but still uncertain) that this regimen is more toxic than other less intensive regimens, and further studies should be undertaken cautiously.
A combination of cisplatin and cytosine arabinoside was used to treat 21 patients with glioblastomas and 5 patients with recurrent grade II gliomas. Cisplatin 60-100 mg/m2 was given I.V. in 250 ml 0.45% saline and preceded by 500 ml dextrose 5% in 0.45% saline. Mannitol 50 g was given I.V. concurrently with the cisplatin. Cytosine arabinoside 500-1000 mg/m2 was given by rapid I.V. infusion immediately after the cisplatin. Of 25 evaluable patients, 10 (40%) experienced objective tumor shrinkage on CT scan, and 6 (24%) stabilized. There were 2 complete remissions. Patients who had had no prior treatment had a higher response rate (58%) than those previously treated (23%). Myelosuppression occurred in some patients 2-3 weeks after treatment. Gastrointestinal toxicity (vomiting and diarrhea) was dose-limiting. Two patients had possible neurological toxicity. Recommended doses for further studies are cisplatin 90 mg/m2 and cytosine arabinoside 900 mg/m2.
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