HIT-LGG: Effektivität von Carboplatin-Vincristin bei progredienten Gliomen niedrigen Malignitätsgrades im Kindesalter - Zwischenbericht

Zusammenfassung.

Hintergrund: Die Therapiestrategie des HIT-LGG-Protokolls prüft, ob für Kinder mit progredienten Gliomen niedrigen Malignitätsgrades im Alter unter 5 Jahren und bei älteren Kindern nach individueller Entscheidung eine Chemotherapie den Beginn einer Standardstrahlentherapie hinauszögern kann.

Patienten und Methoden: Bis 10. 10. 1999 wurden 402 Patienten aus 69 Kliniken gemeldet. 130 Kinder mit progredienten Tumoren wurden nach einer medianen Beobachtungszeit von 5 Monaten behandelt: 46 mit primärer Radiotherapie und 84 mit primärer Chemotherapie. Auf eine 10-wöchige Induktionsphase mit wöchentlichen Vincristingaben und Carboplatinpulsen zu Woche 1, 4, 7 und 10 folgt eine Konsolidierung mit simultaner Medikamentengabe im 4-Wochen-Rhythmus bis Woche 53.

Ergebnisse: Von den 84 Patienten im Chemotherapiearm (49 Jungen, 35 Mädchen, 23 mit NF I, medianes Alter 2,99 Jahre) wurden 36 bei Diagnosestellung und 43 nach einer Beobachtungszeit von median 19,7 Monaten behandelt (5 unbekannt). Klinisch und neuroradiologisch erreichten 94,3 % eine Response nach Protokollkriterien (5 CR, 30 PR/OR, 31 SD), welche im Median nach 5,1 Monaten eintrat. 4 Tumoren waren primär progredient (9 zu früh, 5 unbekannt). Nur 6/84 Kinder wurden bislang bei Progredienz während (2) oder nach (4) Chemotherapie, median nach 25, 6 Monaten, im medianen Alter von 6,0 Jahren bestrahlt. Bei einer medianen Nachbeobachtungszeit von 21,0 Monaten sind 6 Kinder in CR, 11 in PR, 48 in SD, 4 Tumoren sind progredient, 3 Kinder sind verstorben (9 zu früh, 3 unbekannt). Das PFS liegt bei 72 % nach 36 Monaten. 24/27 Kindern mit allergischen Reaktionen auf Carboplatin mussten die Therapie jedoch vorzeitig abbrechen.

Schlussfolgerung: Die Kombination von Carboplatin und Vincristin kann bei Kindern mit progredienten Gliomen niedrigen Malignitätsgrades den Beginn der Strahlentherapie wirkungsvoll hinauszögern. Die hohe Rate an Hypersensitivitätsreaktionen bedarf jedoch zukünftiger Therapiemodifikationen.

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 I, 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 and 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.

Schlüsselwörter:

Niedrig-maligne Gliome - Chemotherapie - Radiotherapie - Carboplatin - Vincristin

Key words:

low-grade glioma - chemotherapy - radiotherapy - Carboplatin - Vincristin

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