ABSTRACT
Patients with malignant gliomas often have safety concerns not common in patients with other types of cancer. Neurologic and cognitive deficits make the care of such patients more complex, with much of the burden of care falling to the primary caretaker and family.
Subject(s)
Cognition Disorders/etiology , Glioma/complications , Patient Care , Safety , Antineoplastic Agents/adverse effects , Brain Edema , Cognition Disorders/chemically induced , Cognition Disorders/drug therapy , Glioma/drug therapy , Glioma/radiotherapy , Humans , Radiotherapy/adverse effects , Seizures/chemically induced , Seizures/drug therapy , Seizures/etiologyABSTRACT
PURPOSE: To define the maximum tolerated dose (MTD) of lenalidomide, an analogue of thalidomide with enhanced immunomodulatory and antiangiogenic properties and a more favorable toxicity profile, in patients with newly diagnosed glioblastoma multiforme (GBM) when given concurrently with radiotherapy. PATIENTS AND METHODS: Patients with newly diagnosed GBM received radiotherapy concurrently with lenalidomide given for 3 weeks followed by a 1-week rest period and continued lenalidomide until tumor progression or unacceptable toxicity. Dose escalation occurred in groups of 6. Determination of the MTD was based on toxicities during the first 12 weeks of therapy. The primary endpoint was toxicity. RESULTS: Twenty-three patients were enrolled, of whom 20 were treated and evaluable for both toxicity and tumor response and 2 were evaluable for toxicity only. Common toxicities included venous thromboembolic disease, fatigue, and nausea. Dose-limiting toxicities were eosinophilic pneumonitis and transaminase elevations. The MTD for lenalidomide was determined to be 15 mg/m(2)/d. CONCLUSION: The recommended dose for lenalidomide with radiotherapy is 15 mg/m(2)/d for 3 weeks followed by a 1-week rest period. Venous thromboembolic complications occurred in 4 patients, and prophylactic anticoagulation should be considered.
Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Thalidomide/analogs & derivatives , Adult , Aged , Antineoplastic Agents/administration & dosage , Combined Modality Therapy , Dose-Response Relationship, Drug , Female , Humans , Lenalidomide , Male , Middle Aged , Pilot Projects , Thalidomide/administration & dosage , Thalidomide/adverse effects , Treatment OutcomeABSTRACT
Antiangiogenic drugs have emerged as effective treatment options for patients with recurrent malignant gliomas (MGs). Though this class of drugs is generally well tolerated, rare life-threatening complications, including thromboembolism, hemorrhage, and gastrointestinal (GI) perforation, are reported. We describe six cases of GI perforation among 244 glioma patients (2.5%) during treatment with antiangiogenic agents in combination with chemotherapy and corticosteroids. Two patients succumbed to this complication, and the others recovered. Because GI perforation is a life-threatening yet treatable complication, neurooncologists must have a low threshold to consider it in patients on antiangiogenic drug therapy who present with abdominal pain and other GI complaints.
