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Lookup NU author(s): Professor Herbie Newell
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We report a multicentre phase II study of orally administered prolonged schedule etoposide in children with refractory or relapsed malignancy. 83 children were entered into the study. The largest diagnostic groups were neuroblastoma (n=20), rhabdomyosarcoma/soft tissue sarcoma (n=16) and brain tumours (n = 16). Etoposide was administered twice daily at a dose of 50mg/m2/day for 21 days using the intravenous preparation given orally. Disease reassessment was performed after the second course. Etoposide plasma concentrations were measured by HPLC, 2 and 6 h after administration of therapy on days 7 and 14 in 15 patients. 61 patients completed two courses and were evaluable for response. There was I complete response (CR), 5 partial responses (PR) 22 stable disease (SD) and 33 progressive disease (PD). Of the 6 with responses, 3 had a diagnosis of medulloblastoma/cerebral primitive neuroectodermal tumour. 24 of 26 patients with SD/PR/CR received further courses with excellent palliative effect. The main toxicity observed was myelosuppression, with 8% and 7% of evaluable courses complicated by grade III-IV neutropenia and thrombocytopenia, respectively. Severe infection (grade III-IV) was rare, complicating only 2/94 evaluable courses. Plasma etoposide median concentrations at 2 h after administration on day 7 of course 1 were 1.5 (range 0.6-2.4) μ/ml. Total course 1 area under the etoposide plasma concentration versus time curve (AUC) values were estimated using a limited sampling model. Grade ≤ 2 leucopenia was only observed in patients with a day 7 2 h etoposide concentration of > 2 μg/ml or a course 1 AUC of > 35 mg/ml.min. It is concluded that given at a dose of 50 mg/m2/day in two doses for 21 day courses, oral etoposide is well tolerated in children. A correlation between drug concentrations and toxicity was observed. Overall, a low response rate was seen (~ 10%), but disease stabilisation appears to occur, and useful palliative effect was frequently noted. The response in brain tumours was more encouraging (3/14 PR) and this group requires further evaluation.
Author(s): Davidson A, Gowing R, Lowis S, Newell DR, Lewis I, Dicks-Mireaux C, Pinkerton CR
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Year: 1997
Volume: 33
Issue: 11
Pages: 1816-1822
Print publication date: 01/10/1997
ISSN (print): 0959-8049
ISSN (electronic): 1879-0852
URL: http://dx.doi.org/10.1016/S0959-8049(97)00201-3
DOI: 10.1016/S0959-8049(97)00201-3
PubMed id: 9470839
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