Patients with recurrent glioblastoma multiforme

Summary

Aim: The objective of this study was to assess the feasibility, dosimetry, tolerability and efficacy of systemically administrated p-[¹³¹I] - iodo-L-phenylalanine (¹³¹IPA) combined with hypo-fractionated external beam radiation therapy (EBRT) in patients with recurrent glioblastoma multiforme (GBM). Patients, methods: Five patients (2 women, 3 men, aged 27-69) with recurrent GBM and exhaustion of regular therapy options were included. All had a positive O-(2-[¹⁸F]Fluoroethyl)- L-tyrosine positron emission tomography (FET-PET) and pretherapeutic dosimetry was performed. Tumour targeting was verified by ¹³¹IPA-SPECT up to six days after radiotracer administration. After ¹³¹IPA therapy, patients were treated with hypo-fractionated EBRT in six fractions of 5 Gy (n = 4) or in eleven fractions of 2 Gy in one case. Results: Based on the individual dosimetry, the patients received a single intravenous administration of 2 to 7 GBq of ¹³¹IPA, resulting in radiation absorbed doses to the blood of 0.80–1.47 Gy. The treatment was well tolerated; only minor complaints of nausea and vomiting that responded to ondansetron and pantoprazol were noticed in the first two patients. After preventive medication, the last three patients had no complaints during therapy. In none of the patients a decrease of leukocyte or thrombocyte counts below the baseline level or the lower normal limit was observed. Tumour doses from ¹³¹IPA were low (≤ 1 Gy) and all patients died three to eight (median 5.5) months after therapy. Conclusion: In this initial experience, treatment of GBM with ¹³¹IPA in combination with EBRT was demonstrated to be safe and well tolerated, but less effective than suggested by the animal studies.

Zusammenfassung

Ziel dieser Studie war es, die Durchführbarkeit, Dosimetrie, Verträglichkeit und Wirksamkeit einer Therapie mit systemisch verabreichtem p-[¹³¹I]Iod-L-phenylalanin (¹³¹IPA) in Kombination mit einer hypo-fraktionierten externer Strahlentherapie (EBRT) bei Patienten mit Glioblastoma multiforme (GBM) zu untersuchen. Patienten, Methoden: Fünf Patienten (2 Frauen, 3 Männer, Alter 27–69 Jahre) mit rezidiviertem GBM wurden nach Ausschöpfung der regulären Therapiemöglichkeiten eingeschlossen. Bei allen lag eine positive O-(2-[¹⁸F]Fluorethyl)-L-tyrosin-Positronenemissionstomographie (FET-PET) vor und eine prätherapeutische Dosimetrie wurde durchgeführt. Die Aufnahme des Tracers in den Tumor wurde mittels ¹³¹IPA-SPECT nach bis zu sechs Tagen nach Tracer-Verabreichung verifiziert. Nach ¹³¹IPA-Therapie wurden die Patienten mit hypo-fraktionierter EBRT in sechs Fraktionen von 5 Gy (n = 4) bzw. in einem Fall in elf Fraktionen von 2 Gy behandelt. Ergebnisse: Abhängig von der individuellen Dosimetrie verabreichten wir den Patienten 2 bis 7 GBq ¹³¹IPA i. v., was zu Blutdosen von 0.80–1.47 Gy führte. Die Behandlung wurde gut vertragen; nur geringfügige Beschwerden von Übelkeit und Erbrechen, die mit Ondansetron und Pantoprazol therapierbar waren, wurden bei den ersten zwei Patienten beobachtet. Unter vorbeugender Medikamentengabe hatten die letzten drei Patienten keine Beschwerden während der Therapie. Bei keinem Patienten zeigte sich nach Therapie ein Abfall der Leukozytenoder Thrombozytenzahl unterhalb des Ausgangswertes oder unterhalb des unteren Referenzwerts. Die Tumordosen durch das ¹³¹IPA blieben niedrig (≤ 1 Gy) und alle Patienten starben drei bis acht (Median 5,5) Monate nach der Therapie. Schlussfolgerung: Die Behandlung des GBM mittels ¹³¹IPA in Kombination mit EBRT erwies sich als sicher und gut verträglich, aber weniger wirksam als es die Tierstudien erhoffen ließen.

Keywords

¹³¹I-phenylalanine - external beam radiation therapy - glioblastoma

Schlüsselwörter

¹³¹I-Phenylalanin - externe Strahlentherapie - Glioblastom

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