A phase 2 feasibility study of sequential, dose intensive chemotherapy to treat progressive low-grade gliomas in children.
BACKGROUND
Low-grade gliomas (LGGs) comprise nearly 35% of pediatric brain tumors and often occur in young children. Many cannot be resected and radiation therapy can be associated with excessive toxicity in children. Centrally located tumors in young children, and those that progress after radiation remain therapeutic challenges. This phase 2 feasibility trial investigated dose intense, sequential chemotherapy in children with LGG.


METHODS
Ten patients less than 21 years of age with progressive LGGs were enrolled. Courses 1 and 4 consisted of carboplatin and etoposide; courses 2 and 5 consisted of cyclophosphamide and vincristine; courses 3 and 6 consisted of lomustine, procarbazine, and vincristine. Dose adjustments were made to maximize dose intensity but minimize toxicity.


RESULTS
Fifty-five of 60 planned chemotherapy courses were administered in 10 patients. One patient with stable disease after 3 courses had complete surgical resection. Two patients taking anticonvulsants experienced prolonged myelosuppression, necessitating removal from study after 5 chemotherapy courses. During 5 of 6 chemotherapy courses, more than 80% of the planned chemotherapy dose intensity was delivered. Two patients had complete responses, 2 patients had partial responses, 3 patients had minor responses, and 3 patients had disease stabilization. No children had life threatening infection or hemorrhage. No patient experienced progressive disease during therapy.


CONCLUSIONS
Administration of sequential, dose intense chemotherapy was feasible and clinically tolerated. Concurrent anticonvulsant therapy limited dose intensity in 2 patients. Although efficacy appeared consistent with published larger series, small patient number in this study precludes definitive conclusions.
Bruggers
Carol S
CS
Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84113, USA. Carol.bruggers@intermountainmail.org
Greene
Dayna
D
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D016896:Treatment Outcome