Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors

Needle, Michael N.; Molloy, Patricia T.; Geyer, J. Russell; Herman-Liu, Alisa; Belasco, Jean B.; Goldwein, Joel W.; Sutton, Leslie N.; Phillips, Peter C.B.

doi:10.1002/(sici)1096-911x(199707)29:1<28::aid-mpo5>3.0.co;2-u

Cited by 98 publications

(32 citation statements)

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“…It is widely used in paediatric brain tumour treatment and given in many different schedules. Oral continuous chemotherapy has recently shown activity in glioma (Chamberlain, 1997;Needle et al, 1997). Combining DNA alkylating agents with topoisomerase inhibitors is frequent practice and partially based on the rationale, that the topoisomerases are necessary for DNA repair mechanisms activated after DNA alkylation.…”

Section: Discussionmentioning

confidence: 99%

Treatment of paediatric pontine glioma with oral trophosphamide and etoposide

Wolff¹,

Westphal²,

Mölenkamp

et al. 2002

Br J Cancer

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To evaluate the overall survival of paediatric patients with pontine gliomas treated with oral trophosphamide and etoposide. Patients between 3 and 17 years of age with either typical diffuse pontine glioma on MRI or histologically proven anaplastic astrocytoma/glioblastoma multiforme located in the pons, were eligible. Treatment consisted of oral trophosphamide 100 mg m 72 day 71 combined with oral etoposide at 25 mg m 72 day 71 starting simultaneously with conventional radiation. Twenty patients were enrolled (median age 6 years, male : female=9 : 11). Surgical procedures included: no surgery: five, open biopsy: three, stereotactic biopsy: six, partial resection: three, and sub-total resection: three. Histological diagnoses included pilocytic astrocytoma: one, astrocytoma with no other specification: three, anaplastic astrocytoma: three, glioblastoma multiforme: eight, no histology: five. The most frequent side effects were haematologic and gastrointestinal. There was no toxic death. The response to combined treatment in 12 evaluable patients was: complete response: 0, partial response: three, stable disease: four, and progressive disease: five. All tumours progressed locally and all patients died. The overall median survival was 8 months. The overall survival rates at 1 and 4 years were: 0.4 and 0.05 respectively. This was not different from a control group of patients documented in the same population. Oral trophosphamide in combination with etoposide did not improve survival of pontine glioma patients. The treatment was well tolerated and should be evaluated for more chemoresponsive paediatric malignancies.

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Section: Discussionmentioning

confidence: 99%

Treatment of paediatric pontine glioma with oral trophosphamide and etoposide

Wolff¹,

Westphal²,

Mölenkamp

et al. 2002

Br J Cancer

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“…A number of clinical trials have used a chronic oral dosing schedule of etoposide, including two previous studies in children with recurrent intracranial ependymomas. [12][13][14][15][16][17]24,25 A variety of regimens have been utilized for recurrent intracranial ependymomas including the "8-in-1" regimen, etoposide, carboplatin, PCV, MOPP (mechlorethamine, vincristine, prednisone, and procarbazine), alternating cyclophosphamide plus vincristine with cisplatin plus etoposide, and autologous bone marrow transplantation. 17,[25][26][27][28][29][30] These studies indicate that chemotherapy has a very modest effect in the setting of recurrent intracranial ependymoma and that no chemotherapy regimen appears to have clear superiority over another.…”

Section: Discussionmentioning

confidence: 99%

Salvage chemotherapy for recurrent spinal cord ependymona

Chamberlain

2002

Cancer

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BACKGROUNDEpendymomas are reported to constitute 4% of all primary central nervous system (CNS) malignancies in adults, 30% of which occur in the spinal cord. A prospective Phase II study to determine toxicity and response to chronic oral etoposide in patients with recurrent low‐grade intramedullary spinal cord ependymoma (SCE) was conducted.METHODSTen patients (6 males and 4 females with a median age of 30 years) with recurrent SCE were treated with oral etoposide (50mg/m2/day given daily for 21 days followed by a 14‐day break and then repeated constituted a cycle of therapy). All patients had failed surgery and radiotherapy and four patients had failed one prior chemotherapy. Blood counts were obtained weekly, and neurologic examination and a chemistry panel were performed monthly. Contrast‐enhanced magnetic resonance imaging of the spine was performed every 8 weeks after a cycle of etoposide and before the next cycle of chemotherapy was initiated.RESULTSTreatment‐related complications included alopecia in 9 patients, nonbloody diarrhea in 6 patients, a baseline weight loss of > 10% in 5 patients, Grade (according to the National Cancer Institute Common Toxicity Scale) 3‐4 neutropenia in 3 patients, Grade 3‐4 thrombocytopenia in 3 patients, and Grade 3‐4 anemia in 2 patients. There were no treatment‐related deaths reported. After 1 cycle of etoposide, 3 patients (30%) demonstrated progressive disease, 2 patients (20%) achieved a partial response, and 5 patients (50%) maintained stable disease. The overall median response or stable disease duration (disease‐free progression) was 15 months (range, 2.5–45+ months). The overall median survival was 17.5 months (range, 3–45+ months).CONCLUSIONSChronic oral etoposide appears to be well tolerated, has modest toxicity, and had apparent activity in the small cohort of adults in the current study with surgically and medically refractory, recurrent, intradural intramedullary SCE. Cancer 2002;95:997–1002. © 2002 American Cancer Society.DOI 10.1002/cncr.10826

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“…Topotecan zeigte keinerlei partielle oder gar komplette Remission, sondern lediglich eine Stabilisierung bei fünf von 17 Ependymomen für eine Dauer von vier bis 18 Kursen [39]. Needle et al [58] beobachtete nach oraler Methotrexatgabe bei zwei von fünf Ependymomen ein komplettes bzw. partielles Ansprechen.…”

Section: Rezidivtherapieunclassified