Meningeal carcinomatosis in patients with breast carcinoma: Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen
Karim FizaziBernard AsselainAnne Vincent‐SalomonMichel JouveVéronique DièrasThao PalangiéPhilippe BeuzebocThierry DorvalP Pouillart
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BACKGROUND This retrospective study evaluates the results of a regimen 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 diagnosed with meningeal carcinomatosis at a mean age of 52 years. All but two had previous metastatic involvement. The proportion of lobular and ductal carcinomas was balanced. Malignant cells were present in cerebrospinal fluid (CSF) samples from 61 patients, whereas the 7 remaining patients had increased CSF protein associated with computerized tomographic scan evidence of meningeal metastases. From 1989, 41 of the patients received a regimen of high-dose intrathecal methotrexate with systemic folinic acid rescue (HD-MTX+FA): intrathecal MTX, 15 mg daily × 5 days, repeated every 2 weeks, and intrathecal hydrocortisone acetate, 125 mg on Day 1, and folinic acid, 10 mg intramuscularly 12 hours after each MTX injection. Systemic treatment and radiation therapy were usually associated. Patients treated before 1988 received intrathecal MTX in conventional doses (15 mg once a week). RESULTS Clinical objective response, defined as a neurological improvement for at least one month, was achieved in 17 patients (41%) and stabilization in 14 (34%) treated with the HD-MTX+FA regimen. The response rate was significantly higher compared with that of the group treated with conventional doses (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 the main toxicity that occurred in 16 patients (39%) treated with the HD-MTX+FA regimen, and in 7 patients (33%) treated with conventional doses of MTX. In a univariate analysis, three parameters were singled out as having a favorable prognostic value for response to therapy: controlled systemic disease at diagnosis (P < 0.05), low initial CSF protein level (P < 0.05), and concomitant systemic chemotherapy during intrathecal therapy (P < 0.02). Multivariate analysis was not performed because the sample size was too small. CONCLUSIONS Although this study was retrospective, the intrathecal HD-MTX+FA regimen appears to be a more efficient strategy than conventional doses of MTX to induce neurologic improvement and perhaps better survival. It should be recommended in combination with systemic chemotherapy for selected patients with meningeal 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. Cancer 1996;77:1315-23.Keywords:
Folinic acid
Meningeal carcinomatosis
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Under the aegis of the Queensland Trophoblastic Tumour Registry, a screening and monitoring programme with the β-subunit of chorionic gonadotrophin as a marker was adopted in the management of patients with gestational trophoblastic disease. Twenty-six patients had been treated with pulses of methotrexate, followed by folinic acid rescue, up to a total dose of 200 mg of methotrexate in each course; the side effects were minor and infrequent. This regimen was effective in producing biochemical and clinical remission in 18 of 19 patients both with non-metastatic and with metastatic persistent disease; the mean duration of treatment was nine weeks and 19.2 weeks respectively. However, it was effective in only three of seven patients with histologically confirmed choriocarcinoma, which suggests that a more aggressive multidrug regimen should be considered from the outset in this high risk group of patients. Our preliminary data have revealed no permanent effects on subsequent fertility or observable effects on the babies so far studied.
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BACKGROUND This retrospective study evaluates the results of a regimen 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 diagnosed with meningeal carcinomatosis at a mean age of 52 years. All but two had previous metastatic involvement. The proportion of lobular and ductal carcinomas was balanced. Malignant cells were present in cerebrospinal fluid (CSF) samples from 61 patients, whereas the 7 remaining patients had increased CSF protein associated with computerized tomographic scan evidence of meningeal metastases. From 1989, 41 of the patients received a regimen of high-dose intrathecal methotrexate with systemic folinic acid rescue (HD-MTX+FA): intrathecal MTX, 15 mg daily × 5 days, repeated every 2 weeks, and intrathecal hydrocortisone acetate, 125 mg on Day 1, and folinic acid, 10 mg intramuscularly 12 hours after each MTX injection. Systemic treatment and radiation therapy were usually associated. Patients treated before 1988 received intrathecal MTX in conventional doses (15 mg once a week). RESULTS Clinical objective response, defined as a neurological improvement for at least one month, was achieved in 17 patients (41%) and stabilization in 14 (34%) treated with the HD-MTX+FA regimen. The response rate was significantly higher compared with that of the group treated with conventional doses (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 the main toxicity that occurred in 16 patients (39%) treated with the HD-MTX+FA regimen, and in 7 patients (33%) treated with conventional doses of MTX. In a univariate analysis, three parameters were singled out as having a favorable prognostic value for response to therapy: controlled systemic disease at diagnosis (P < 0.05), low initial CSF protein level (P < 0.05), and concomitant systemic chemotherapy during intrathecal therapy (P < 0.02). Multivariate analysis was not performed because the sample size was too small. CONCLUSIONS Although this study was retrospective, the intrathecal HD-MTX+FA regimen appears to be a more efficient strategy than conventional doses of MTX to induce neurologic improvement and perhaps better survival. It should be recommended in combination with systemic chemotherapy for selected patients with meningeal 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. Cancer 1996;77:1315-23.
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This report describes a woman with a cornual pregnancy, documented by laparoscopy and ultrasonography, who was successfully treated with a 1-day high-dose methotrexate regimen and folinic acid rescue. The serum Β-hCG level was 2,260 and increased to 3,060 IU/1 on the 5th day after treatment before it fell precipitously to below 250IU/1 15 days after methotrexate treatment. No side effects were experienced by the patient.
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Objective To investigate the effect of PR expression on the sensitivity of chemotherapy with TC regimen in locally advanced breast cancer patients.Methods The expression of PR was detected by EnVision immunohistochemistry in breast cancer tissues before neoadjuvant chemotherapy with TC regimen in corresponding patients,and the correlation of PR expression with the sensitivity of chemotherapy were studied in 57 PR negative or positive patients.Results The sensitivity was 81.48%(22/27)in PR negative breast tumours,and was 53.33%(16/30) in PR positive breast tumours with TC regimen in locally advanced breast cancer patients,and there was significant difference of sensitivity between breast cancer patients with PR negative and positive tumours(P0.05).Conclusion PR negative breast cancer patients were more sensitive to neoadjuvant chemotherapy.PR negative may serve as one of good markers for prediction of sensitivity of neoadjuvant chemotherapy with TC regimen in locally advanced breast cancer patients.
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This report describes a woman with a cornual pregnancy, documented by laparoscopy and ultrasonography, who was successfully treated with a 1-day high-dose methotrexate regimen and folinic acid rescue. The serum β-hCG level was 2,260 and increased to 3,060 IU/1 on the 5th day after treatment before it fell precipitously to below 250IU/1 15 days after methotrexate treatment. No side effects were experienced by the patient.
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Forty-two patients with measurable advanced colorectal cancer were treated with sequential methotrexate (Mtx) and 5-fluorouracil (5-FU), followed by folinic acid rescue. Twenty-one patients had received prior chemotherapy, mainly 5-FU (group 1) and remaining 21 patients had not been previously treated by cytotoxic agents (group 2). Two different treatment schedules were used. Regimen I (27 patients): MTX 250 mg/m2 was infused over 1 hour. Two hours from start 5-FU 600 mg/m2 was given as intravenous bolus. Folinic acid rescue started 24 hours after MTX infusion. Regimen II (15 patients): MTX 250 mg/m2 was given as 1-hour infusion. Three hours after the start of MTX a 46-hour 5-FU infusion (2000 mg/m2) was started. Folinic acid rescue as in regimen I. The chemotherapy courses were repeated every second week. After 3 cycles only one patient had partial response, 33 had no change and 8 progressive disease. The median time until progression was 2 1/2 months in group 1 and 4 months in group 2. The median survival was 7 months in group 1 and 10 1/2 months in group 2. Almost identical results were obtained by the two treatment schedules. The toxicity of both regimens was low.
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Interstitial pregnancy
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