Combined intraommaya methotrexate, cytosine arabinoside, hydrocortisone and thio-TEPA for meningeal involvement by malignancies

Abstract

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.

ATR inhibition selectively sensitizes G 1 checkpoint-deficient cells to lethal premature chromatin condensation

“…Caffeine has been shown in vitro to selectively radiosensitize cancer cells (26) and, in fact, has been investigated in humans with incurable cancer. Unfortunately, because of its lack of specificity, caffeine causes seizures in humans at doses less than are required for inhibition of the replication checkpoint (27). A further implication of these studies is that an ideal ATR inhibitor would not affect ATM function, as this would have the undesirable effect of diminishing ATM-dependent p53͞G 1 arrest in normal cells, making them more sensitive to ATR inhibition.…”

Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment

“…Controversy in the literature about their predicting relevance exists for a decreased CSF g l~c o s e~-'~ a normal or increased CSF protein,7r9"4 the presenting neurologic symptoms and dy~function~~''~''~~~~~~ and concurrent RT.7314, 27 The main reason for these controversies seems to be that until now the studies lack a sufficient number of uniformly treated patients with one specific primary tumor to make reliable and significant conclusions. Moreover, the criteria for the diagnosis of MC are not uniform, i.e., in some studies CSF cytologic study is not the decisive factor for making the diagno~is.…”

Leptomeningeal metastasis: survival and prognostic factors in 155 patients

“…If the analysis was restricted to the group of 105 patients with non-CNS primary tumors and patients with primary brain tumors and PCNSL were excluded, the same prognostic factors were found as for the entire cohort: age [relative risk (RR) 0.75, 95% confidence interval (CI) 0. 58 In a multivariate analysis of the entire cohort, the application of systemic chemotherapy was confirmed as predictors of favourable outcome. If multivariate analysis was only applied to patients with systemic tumors metastatic to the CNS and the patients with primary brain tumors and PCNSL were omitted from analysis, the application of systemic chemotherapy was confirmed as a positive prognostic factor (risk ratio 1.39, 95% CI 1.01 -2.00, p = 0.046).…”