Topotecan for the treatment of recurrent or progressive central nervous system tumors - a pediatric oncology group phase II study

• Published in: Journal of neuro-oncology Vol. 43; no. 1; pp. 43 - 47
• Main Authors: KADOTA, R. P, STEWART, C. F, HORN, M, KUTTESCH, J. F, BURGER, P. C, KEPNER, J. L, KUN, L. E, FRIEDMAN, H. S, HEIDEMAN, R. L
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.05.1999; Springer Nature B.V
• Subjects: Adult; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - metabolism; Central Nervous System Neoplasms - pathology; Chemotherapy; Child; Disease Progression; Dose-Response Relationship, Drug; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - therapeutic use; Humans; Magnetic Resonance Imaging; Medical sciences; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Pharmacology. Drug treatments; Tomography, X-Ray Computed; Topotecan - adverse effects; Topotecan - pharmacokinetics; Topotecan - therapeutic use; Human; Antineoplastic agent; Nervous system diseases; Relapse; Enzyme; DNA topoisomerase; Enzyme inhibitor; Topotecan; Malignant tumor; Cerebral disorder; Progressive; Chemotherapy; Isomerases; Treatment; Central nervous system disease; Phase II trial; Child; Brain (vertebrata)
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1023/A:1006294102611

Topotecan was studied as a 72 h infusion given every 3 weeks. Treatment began at a dose of 1.0 mg/m2/day and was increased to 1.25 mg/m2/day after the first 6 patients tolerated this higher dose without excessive toxicities. Eighty-eight evaluable children were accrued in 6 strata. There were no complete nor partial responses. Twenty subjects had stable disease (astrocytoma 5/11, malignant glioma 5/13, medulloblastoma 0/12, brain stem tumor 4/19, ependymoma 5/17, and miscellaneous histologies 1/16). Two patients (astrocytoma, ependymoma) completed the maximum 18 topotecan courses. The remaining 68 children developed progressive disease within 2 months. Myelosuppression was the main toxicity. Grade 4 leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 18, 32, 5, and 23 participants, respectively. It was concluded that topotecan as given according to this schedule showed insufficient activity to promote it to frontline protocol usage.