Judith van Loon1, Aniek J G Even2, Hugo J W L Aerts3, Michel Öllers2, Frank Hoebers2, Wouter van Elmpt2, Ludwig Dubois2, Anne-Marie C Dingemans4, Roy I Lalisang5, Pascal Kempers6, Boudewijn Brans6, Véronique Winnepenninckx7, Ernst-Jan Speel7, Eric Thunnissen8, Kim M Smits2, Ronald Boellaard9, Danielle J Vugts9, Dirk De Ruysscher10, Philippe Lambin2. 1. Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. Electronic address: Judith.vanloon@maastro.nl. 2. Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. 3. Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands; Departments of Radiation Oncology and Radiology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. 4. Department of Pulmonology, Maastricht University Medical Centre, The Netherlands. 5. Department of Medical Oncology, Maastricht University Medical Centre, The Netherlands. 6. Department of Nuclear Medicine, Maastricht University Medical Centre, The Netherlands. 7. Department of Pathology, Maastricht University Medical Centre, The Netherlands. 8. Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands. 9. Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands. 10. Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands; Department of Radiation Oncology, University Hospital Leuven, KU Leuven, Belgium.
Abstract
BACKGROUND AND PURPOSE: PET imaging of cetuximab uptake may help selecting cancer patients with the highest chance of benefit. The aim of this phase I trial was to determine the safety of the tracer 89Zr-cetuximab and to assess tumour uptake. METHODS: Two dose schedules were used; two consecutive doses of 60MBq 89Zr-cetuximab or a single dose of 120MBq, both preceded by 400mg/m2 of unlabelled cetuximab. Toxicity (CTCAE 3.0) was scored twice weekly. PET-CT scans were acquired on days 4, 5 and 6 (step 1) or 5, 6, 7 (step 2). Because tumour uptake could not be assessed satisfactorily, a third step was added including EGFR overexpressing tumours. RESULTS: Nine patients were included (6 NSCLC; 3 HNC). No additional toxicity was associated with administration of 89Zr-cetuximab compared to standard cetuximab. A tumour to blood ratio (TBR)>1 was observed in all but one patient, with a maximum of 4.56. TBR was not different between dose schedules. There was a trend for higher TBR at intervals>5days after injection. CONCLUSIONS: Both presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60MBq, with a minimum time interval for scanning of 6days.
BACKGROUND AND PURPOSE: PET imaging of cetuximab uptake may help selecting cancerpatients with the highest chance of benefit. The aim of this phase I trial was to determine the safety of the tracer 89Zr-cetuximab and to assess tumour uptake. METHODS: Two dose schedules were used; two consecutive doses of 60MBq 89Zr-cetuximab or a single dose of 120MBq, both preceded by 400mg/m2 of unlabelled cetuximab. Toxicity (CTCAE 3.0) was scored twice weekly. PET-CT scans were acquired on days 4, 5 and 6 (step 1) or 5, 6, 7 (step 2). Because tumour uptake could not be assessed satisfactorily, a third step was added including EGFR overexpressing tumours. RESULTS: Nine patients were included (6 NSCLC; 3 HNC). No additional toxicity was associated with administration of 89Zr-cetuximab compared to standard cetuximab. A tumour to blood ratio (TBR)>1 was observed in all but one patient, with a maximum of 4.56. TBR was not different between dose schedules. There was a trend for higher TBR at intervals>5days after injection. CONCLUSIONS: Both presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60MBq, with a minimum time interval for scanning of 6days.
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Authors: Aniek J G Even; Olga Hamming-Vrieze; Wouter van Elmpt; Véronique J L Winnepenninckx; Jolien Heukelom; Margot E T Tesselaar; Wouter V Vogel; Ann Hoeben; Catharina M L Zegers; Daniëlle J Vugts; Guus A M S van Dongen; Harry Bartelink; Felix M Mottaghy; Frank Hoebers; Philippe Lambin Journal: Oncotarget Date: 2017-01-17