PET imaging of zirconium-89 labelled cetuximab: A phase I trial in patients with head and neck and lung cancer

Judith van Loon; Aniek J. G. Even; Hugo J. W. L. Aerts; Michel Ollers; Frank Hoebers; Wouter van Elmpt; Ludwig Dubois; Anne-Marie C. Dingemans; Roy I. Lalisang; Pascal Kempers; Boudewijn Brans; Veronique Winnepenninckx; Ernst-Jan Speel; Eric Thunnissen; Kim M. Smits; Ronald Boellaard; Danielle J. Vugts; Dirk De Ruysscher; Philippe Lambin

doi:10.1016/j.radonc.2016.11.020

PET imaging of zirconium-89 labelled cetuximab: A phase I trial in patients with head and neck and lung cancer

Judith van Loon^*, Aniek J. G. Even, Hugo J. W. L. Aerts, Michel Ollers, Frank Hoebers, Wouter van Elmpt, Ludwig Dubois, Anne-Marie C. Dingemans, Roy I. Lalisang, Pascal Kempers, Boudewijn Brans, Veronique Winnepenninckx, Ernst-Jan Speel, Eric Thunnissen, Kim M. Smits, Ronald Boellaard, Danielle J. Vugts, Dirk De Ruysscher, Philippe Lambin

^*Corresponding author for this work

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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 (89)zr-cetuximab and to assess tumour uptake.

Methods: Two dose schedules were used; two consecutive doses of 60 MBq Zr-89-cetuximab or a single dose of 120 MBq, both preceded by 400 mg/m(2) 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 > 5 days after injection.

Conclusions: Both presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60 MBq, with a minimum time interval for scanning of 6 days. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Original language	English
Pages (from-to)	267-273
Number of pages	7
Journal	Radiotherapy and Oncology
Volume	122
Issue number	2
DOIs	https://doi.org/10.1016/j.radonc.2016.11.020
Publication status	Published - Feb 2017

Keywords

Zr-89-cetuximab
EGFR
Immuno-PET
Phase I trial
GROWTH-FACTOR RECEPTOR
MONOCLONAL-ANTIBODIES
PLUS CETUXIMAB
1ST-LINE CHEMOTHERAPY
EGFR-INHIBITION
IMMUNO-PET
EXPRESSION
RADIOTHERAPY
CARCINOMA
SURVIVAL

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van Loon, J., Even, A. J. G., Aerts, H. J. W. L., Ollers, M., Hoebers, F., van Elmpt, W., Dubois, L., Dingemans, A.-M. C., Lalisang, R. I., Kempers, P., Brans, B., Winnepenninckx, V., Speel, E.-J., Thunnissen, E., Smits, K. M., Boellaard, R., Vugts, D. J., De Ruysscher, D., & Lambin, P. (2017). PET imaging of zirconium-89 labelled cetuximab: A phase I trial in patients with head and neck and lung cancer. Radiotherapy and Oncology, 122(2), 267-273. https://doi.org/10.1016/j.radonc.2016.11.020

@article{58d31ff2271a4f19adfab2c44087a423,

title = "PET imaging of zirconium-89 labelled cetuximab: A phase I trial in patients with head and neck and lung cancer",

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 (89)zr-cetuximab and to assess tumour uptake.Methods: Two dose schedules were used; two consecutive doses of 60 MBq Zr-89-cetuximab or a single dose of 120 MBq, both preceded by 400 mg/m(2) 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 > 5 days after injection.Conclusions: Both presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60 MBq, with a minimum time interval for scanning of 6 days. (C) 2016 Elsevier Ireland Ltd. All rights reserved.",

keywords = "Zr-89-cetuximab, EGFR, Immuno-PET, Phase I trial, GROWTH-FACTOR RECEPTOR, MONOCLONAL-ANTIBODIES, PLUS CETUXIMAB, 1ST-LINE CHEMOTHERAPY, EGFR-INHIBITION, IMMUNO-PET, EXPRESSION, RADIOTHERAPY, CARCINOMA, SURVIVAL",

author = "{van Loon}, Judith and Even, {Aniek J. G.} and Aerts, {Hugo J. W. L.} and Michel Ollers and Frank Hoebers and {van Elmpt}, Wouter and Ludwig Dubois and Dingemans, {Anne-Marie C.} and Lalisang, {Roy I.} and Pascal Kempers and Boudewijn Brans and Veronique Winnepenninckx and Ernst-Jan Speel and Eric Thunnissen and Smits, {Kim M.} and Ronald Boellaard and Vugts, {Danielle J.} and {De Ruysscher}, Dirk and Philippe Lambin",

year = "2017",

month = feb,

doi = "10.1016/j.radonc.2016.11.020",

language = "English",

volume = "122",

pages = "267--273",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

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van Loon, J , Even, AJG , Aerts, HJWL, Ollers, M, Hoebers, F , van Elmpt, W , Dubois, L, Dingemans, A-MC, Lalisang, RI, Kempers, P, Brans, B, Winnepenninckx, V , Speel, E-J, Thunnissen, E, Smits, KM, Boellaard, R, Vugts, DJ, De Ruysscher, D & Lambin, P 2017, 'PET imaging of zirconium-89 labelled cetuximab: A phase I trial in patients with head and neck and lung cancer', Radiotherapy and Oncology, vol. 122, no. 2, pp. 267-273. https://doi.org/10.1016/j.radonc.2016.11.020

TY - JOUR

T1 - PET imaging of zirconium-89 labelled cetuximab

T2 - A phase I trial in patients with head and neck and lung cancer

AU - van Loon, Judith

AU - Even, Aniek J. G.

AU - Aerts, Hugo J. W. L.

AU - Ollers, Michel

AU - Hoebers, Frank

AU - van Elmpt, Wouter

AU - Dubois, Ludwig

AU - Dingemans, Anne-Marie C.

AU - Lalisang, Roy I.

AU - Kempers, Pascal

AU - Brans, Boudewijn

AU - Winnepenninckx, Veronique

AU - Speel, Ernst-Jan

AU - Thunnissen, Eric

AU - Smits, Kim M.

AU - Boellaard, Ronald

AU - Vugts, Danielle J.

AU - De Ruysscher, Dirk

AU - Lambin, Philippe

PY - 2017/2

Y1 - 2017/2

N2 - 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 (89)zr-cetuximab and to assess tumour uptake.Methods: Two dose schedules were used; two consecutive doses of 60 MBq Zr-89-cetuximab or a single dose of 120 MBq, both preceded by 400 mg/m(2) 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 > 5 days after injection.Conclusions: Both presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60 MBq, with a minimum time interval for scanning of 6 days. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

AB - 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 (89)zr-cetuximab and to assess tumour uptake.Methods: Two dose schedules were used; two consecutive doses of 60 MBq Zr-89-cetuximab or a single dose of 120 MBq, both preceded by 400 mg/m(2) 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 > 5 days after injection.Conclusions: Both presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60 MBq, with a minimum time interval for scanning of 6 days. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

KW - Zr-89-cetuximab

KW - EGFR

KW - Immuno-PET

KW - Phase I trial

KW - GROWTH-FACTOR RECEPTOR

KW - MONOCLONAL-ANTIBODIES

KW - PLUS CETUXIMAB

KW - 1ST-LINE CHEMOTHERAPY

KW - EGFR-INHIBITION

KW - IMMUNO-PET

KW - EXPRESSION

KW - RADIOTHERAPY

KW - CARCINOMA

KW - SURVIVAL

U2 - 10.1016/j.radonc.2016.11.020

DO - 10.1016/j.radonc.2016.11.020

M3 - Article

C2 - 28012793

SN - 0167-8140

VL - 122

SP - 267

EP - 273

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

IS - 2

ER -