ABSTRACT
The efficacy of surgery and radiation has been well validated in the treatment of meningiomas, with efficacy depending on tumor pathology, size, symptomatology and rate of progression. The role of medical therapy has the least amount of data but is being increasingly investigated for tumors that are inoperable or those tumors that recur and/or progress despite standard therapy. In this review, current data on the use of chemotherapeutic agents in the management of meningiomas will be reviewed, including cytotoxic, biologic, targeted molecular and hormonal agents.
Subject(s)
Antineoplastic Agents , Disease Management , Meningeal Neoplasms , Meningioma , Antineoplastic Agents/adverse effects , Humans , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/therapy , Meningioma/diagnosis , Meningioma/therapyABSTRACT
PURPOSE: A phase II study was undertaken in patients with recurrent malignant glioma to determine the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, dosed at the respective maximum-tolerated dose (MTD) for patients receiving and not receiving enzyme-inducing antiepileptic drugs (EIAEDs). Because tipifarnib undergoes extensive hepatic metabolism, MTD is doubled in patients on EIAEDs. The population included 67 patients with glioblastoma multiforme (GBM) and an exploratory group of 22 patients with anaplastic glioma (AG). PATIENTS AND METHODS: Patients received tipifarnib (300 and 600 mg bid for 21 days every 4 weeks in non-EIAED and EIAED patients, respectively). All patients were assessable for efficacy and safety. RESULTS: Two AG patients (9.1%) and eight GBM patients (11.9%) had progression-free survival (PFS) more than 6 months. Among the latter eight GBM patients, six of 36 patients (16.7%; 95% CI, 7% to 32%) were not receiving EIAEDs and two of 31 patients (6.5%; 95% CI, 1% to 20%) were receiving EIAEDs. Four patients had partial responses in group A GBM and one patient had a partial response group B GBM. An exploratory comparison of PFS between GBM groups A and B was statistically significant (P = .01). Patients not receiving EIAEDs had a higher incidence and increased severity of hematologic events. However, the incidence and severity of rash (the previously determined dose-limiting toxicity in patients receiving EIAEDs) seemed similar in EIAED and non-EIAED subgroups. CONCLUSION: Tipifarnib (300 mg bid for 21 days every 4 weeks) shows modest evidence of activity in patients with recurrent GBM who are not receiving EIAEDs and is generally well tolerated in this population.
