ABSTRACT
BACKGROUND: Current bevacizumab-based regimens have failed to improve survival in patients with recurrent glioblastoma. To improve treatment efficacy, we evaluated bevacizumab + BKM120, an oral pan-class I PI3K inhibitor, in this patient population. METHODS: A brief phase I study established the optimal BKM120 dose to administer with standard-dose bevacizumab. BKM120 60 mg PO daily + bevacizumab 10 mg/kg IV every 2 weeks in 28-day cycles was then administered to patients with relapsed/refractory glioblastoma in the phase II portion. RESULTS: Eighty-eight patients enrolled (phase I, 12; phase II, 76). In phase I, BKM120 80 mg PO daily produced dose limiting toxicity in 3 of 6 patients; a BKM120 dose of 60 mg PO daily was established as the maximum tolerated dose. In phase II, the median progression-free survival (PFS) was 4.0 months (95% CI 3.4, 5.4), PFS at 6 months was 36.5%, and the overall response rate was 26%. Forty-two patients (57%) experienced one or more serious treatment related toxicities. The most common CNS toxicities included mood alteration (17%) and confusion (12%); however, these were often difficult to classify as treatment- versus tumor-related. CONCLUSIONS: The efficacy seen in this study is similar to the efficacy previously reported with single-agent bevacizumab. This regimen was poorly tolerated, despite the low daily dose of BKM120. Further development of this combination for the treatment of glioblastoma is not recommended.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/drug effects , Glioblastoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasms/drug therapy , Phosphatidylinositol 3-Kinases/chemistry , Salvage Therapy , Adult , Aged , Aged, 80 and over , Aminopyridines/administration & dosage , Bevacizumab/administration & dosage , Female , Follow-Up Studies , Glioblastoma/pathology , Humans , Male , Maximum Tolerated Dose , Middle Aged , Morpholines/administration & dosage , Neoplasm Recurrence, Local/pathology , Neoplasms/pathology , Prognosis , Survival RateABSTRACT
Children with cancer experience repeated invasive and painful medical procedures. Pain and distress does not decrease with repeated procedures and may worsen if pain is not adequately managed. In 1990, the first recommendations on the management of pain and anxiety associated with procedures for children with cancer were published. Guiding principles described in the recommendations continue to hold true today: maximize comfort and minimize pain, use nonpharmacologic and pharmacologic interventions, prepare the child and family, consider the developmental age of the child, support family and child involvement, assure provider competency in performing procedures and sedation, and use appropriate monitoring to assure safety. This article reviews these key components for managing painful procedures in children and reviews the latest pharmacological and nonpharmacological interventions most effective in minimizing pain and discomfort.
