Antiangiogenic therapy in pediatric malignancies: experience of the Northern Israel Pediatric Cancer Center

MWB Arush MD a, S Postovsky MD a, R Elhasid MD a, A Ben Barak MD a, C Levine MD a, JF Guilburd MD b.

a Department of Pediatric Hemato-Oncology b Pediatric Neurosurgery Unit Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Aims: (1) To demonstrate whether angiogenesis inhibitors prolong survival in children who developed several recurrences under conventional therapies. (2) To observe tolerance and toxicity of the drugs and quality of life of patients. Methods: Sixteen patients (pts) [8 boys, 8 girls; median age: 11 years (y) (range, 3-20 y)] entered the study, all of whom had developed recurrences or tumor progression (TP) after conventional treatments. Ten pts were diagnosed with brain tumor, five with metastatic sarcoma, one with growing teratoma. Treatment was stopped if the pt developed tumor progression or severe toxicity. Nine pts received tamoxifen (TA) 60-80 mg/m2/day, two received thalidomide 200 mg/day, one received TNP 470 50 mg/m2/day, one received shark cartilage extract and one received Interferon+TA. Chemotherapy+TA was delivered to four pts. Median follow up was 12.3 m (range, 2-36 m). Results: Seven pts are alive with stable disease (SD), two pts are alive with TP, and seven pts died of disease. After four local recurrences, one pt with ependymoma was in complete remission under TA for two years. One pt with high grade glioma was with SD for 15 m on TA, and one pt with sarcoma was with SD under TNP 470 for 13 m. Most pts attended school during treatment and did not develop any significant toxicity. Conclusions: Potential application of antiangiogenic compounds may include maintenance therapy in pts at risk of recurrence or to stabilize pts with evidence of disease without disturbing their quality of life.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Angiogenesis.