HIT-LGG: Therapy protocol for the treatment of children with low-grade glioma - Interim report.

Background: The rationale of the HIT-LGG protocol is to delay standard radiotherapy through administration of chemotherapy for children with progressive low grade glioma at an age under 5 years and in older children upon individual decision. Patients and Method: Until October 10th., 1999, 402 patients from 69 hospitals were registered. 130 children with progressive tumors were treated after a median observation time of 5 months: 46 patients received primary radiotherapy and 84 primary chemotherapy. A ten week induction period with weekly Vincristine and pulses of Carboplatin at weeks 1, 4, 7 and 10 is followed by consolidation with simultaneous application of both drugs every 4 weeks until week 53. Results: Of 84 patients in the chemotherapy arm of the study (49 male, 35 female, 23 NF 1, median age 2.99 years) 36 received treatment at diagnosis and 43 after a median observation time of 19.7 months. 94,3% achieved a clinical and neuroradiological response according to protocol criteria (5 CR, 30 PR/OR, 31 SD) after a median of 5.1 months. 4 tumors showed primary progression (9 too early, 5 not known). Only 6 of 84 children received radiation therapy for progressive disease during (2) or after termination (4) of chemotherapy, after a median delay of 25.6 months at a median age of 6.0 years. At a median observation time of 21.0 months, 6 children are in CR, 11 in PR, 48 have SD, 4 tumors are progressive and 3 children died of their tumor. (9 too early, 3 not known). PFS is at 72% after 36 months. 24 of 27 children experiencing allergic reactions to Carboplatin had to interrupt chemotherapy prematurely. Conclusions: Combination therapy with Carboplatin acid Vincristine can effectively delay the start of radiotherapy in children with progressive low-grade glioma. The high rate of hypersensitivity reactions has to prompt future modifications of treatment.