Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy

Abstract

Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.

Optic pathway gliomas: a review

“…Temozolomide has also been shown to be useful in stabilizing disease in more than 50% of patients without significant toxicity 26 and is considered an option in patients with progressive OPG in whom first-line therapy has failed. Petronio et al 67 addressed the use of a 5-drug regimen consisting of 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and vincristine for treatment of OPG, and they obtained favorable results. A similar regimen in which dibromodulcitol was excluded was compared with the standard regimen of carboplatin and vincristine in 2003 and was deemed a reasonable second-line therapy for patients with OPG.…”

Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

“…A variety of drugs have been used, including vincristine, actinomycin D, etoposide, carmustine, and carboplatin, as well as combination regimens consisting of these drugs (R. Prados, personal communication, 1996). [5,14,17,18,20,21,24] In 1989, a study was begun to evaluate the efficacy of combining carboplatin and vincristine in treating children with recurrent and newly diagnosed astrocytomas. The objective response rates of 60 children, including 37 with newly diagnosed astrocytomas, have been reported.…”

Advances in treatment of pediatric brain tumors

“…These pilot trials reported regression or stability of tumors in 75-90% of patients. [82][83][84] At follow-up, children treated on the carboplatin/vincristine regimen before age 5 years, had a 75% 4-year PFS rate. 85 The outcome of a recently-closed COG phase III randomized trial comparing the latter two of these regimens is pending.…”