MENINGEAL CARCINOMATOSIS IN PATIENTS WITH BREAST-CARCINOMA - CLINICAL-FEATURES, PROGNOSTIC FACTORS, AND RESULTS OF A HIGH-DOSE INTRATHECAL METHOTREXATE REGIMEN

BACKGROUND. This retrospective study evaluates the results of a regime n of high-dose intrathecal methotrexate and the prognostic factors for response in patients with meningeal metastases from breast carcinoma. METHODS. From 1979 to 1994, 68 breast carcinoma patients were diagnos ed with meningeal carcinomatosis at a mean age of 52 years. All but tw o had previous metastatic involvement. The proportion of lobular and d uctal carcinomas was balanced. Malignant cells were present in cerebro spinal fluid (CSF) samples from 61 patients, whereas the 7 remaining p atients had increased CSF protein associated with computerized tomogra phic scan evidence of meningeal metastases. From 1989, 41 of the patie nts received a regimen of high-dose intrathecal methotrexate with syst emic folinic acid rescue (HD-MTX+FA): intrathecal MTX, 15 mg daily x 5 days, repeated every 2 weeks, and intrathecal hydrocortisone acetate, 125 mg on Day 1, and folinic acid, 10 mg intramuscularly 12 hours aft er each MTX injection. Systemic treatment and radiation therapy were u sually associated. Patients treated before 1988 received intrathecal M TX in conventional doses (15 mg once a week). RESULTS. Clinical object ive response, defined as a neurological improvement for at least one m onth, was achieved in 17 patients (41%) and stabilization in 14 (34%) treated with the HD-MTX+FA regimen. The response rate was significantl y higher compared with that of the group treated with conventional dos es (P = 0.03). Median survival was 14 weeks for patients treated with the HD-MTX+FA regimen, compared with 7 weeks for patients who received conventional doses of MTX (P = 0.01). Grade 3 or 4 neutropenia was th e main toxicity that occurred in 16 patients (39%) treated with the HD -MTX+FA regimen, and in 7 patients (33%) treated with conventional dos es of MTX In a univariate analysis, three parameters were singled out as having a favorable prognostic value for response to therapy: contro lled systemic disease at diagnosis (P < 0.05), low initial CSF protein level (P < 0.05), and concomitant systemic chemotherapy during intrat hecal therapy (P < 0.02). Multivariate analysis was not performed beca use the sample size was too small. CONCLUSIONS. Although this study wa s retrospective, the intrathecal HD-MTX+FA regimen appears to be a mor e efficient strategy than conventional doses of MTX to induce neurolog ic improvement and perhaps better survival. It should be recommended i n combination with systemic chemotherapy for selected patients with me ningeal carcinomatosis from breast carcinoma who are likely to benefit from intensive therapy, i.e., patients with a CSF protein level less than 5 g/L and in whom systemic disease has been controlled. (C) 1996 American Cancer Society.