Reinfusion of unprocessed, granulocyte colony-stimulating factor-stimulated whole blood allows dose escalation of 186relabeled chimeric monoclonal antibody U36 radioimmunotherapy in a phase I dose escalation study

David R. Colnot, Gert J. Ossenkoppele, Jan C. Roos, Jasper J. Quak, Remco De Bree, Pontus K. Börjesson, Peter C. Huijgens, Gordon B. Snow, Guus A M S Van Dongen

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Abstract

Purpose: In an earlier Phase I radioimmunotherapy (RIT) study with rhenium-186-labeled chimeric monoclonal antibody (cMAb) U36 in patients with refractory head and neck squamous cell carcinoma, the maximum tolerated activity was established at 1.0 GBq/m2, at which bone marrow doses ranged from 0.7 to 1.1 Gy. In the present study, further dose escalation in RIT was evaluated using a facile method of reinfusion of granulocyte colony-stimulating factor (G-CSF)-stimulated unprocessed whole blood. Experimental Design: Nine patients with recurrent or metastatic head and neck squamous cell carcinoma were treated at radiation dose levels of 1.0, 1.5, and 2.0 GBq/m2. Before RIT, G-CSF (10 μg/kg/day) was administered s.c. at home during 5 days. On day 6, just before administration of 186Relabeled cMAb U36, 1 liter of whole blood was harvested and kept unprocessed at 4°C until reinfusion after 72 h. Blood samples were taken for analysis of pharmacokinetics and bone marrow dosimetry. Patients were evaluated for myelotoxicity and tumor response. Results: Blood harvesting, RIT, and reinfusion of whole blood were well tolerated by all patients. G-CSF stimulation resulted in a mean of 0.41 × 106 CD34+ cells/kg (range, 0.15-0.83 × 106 CD34+ cells/kg) and a mean committed colony-forming units granulocyte macrophage count of 5.62 × 104/kg (range, 0.62-13.37 × 104/kg). The mean biological half-life of 186Relabeled cMAb U36 in blood was 72.6 ± 16.0 h, and bone marrow doses ranged from 2.1 to 2.8 Gy at the highest dose level. Myelotoxicity exceeding grade 3 was not observed. Stable disease was observed in five of nine patients, ranging from 3 to 5 months, and was still ongoing in one of these patients. Conclusions: This study indicates that a doubling of the maximum tolerated activity and bone marrow dose of 186Relabeled cMAb U36 can be achieved using reinfusion of GCSF-stimulated unprocessed whole blood.

Original languageEnglish
Pages (from-to)3401-3406
Number of pages6
JournalClinical Cancer Research
Volume8
Issue number11
Publication statusPublished - 1 Nov 2002

Cite this

@article{6f9ad8a8dc5341c59d20f48ba00beab6,
title = "Reinfusion of unprocessed, granulocyte colony-stimulating factor-stimulated whole blood allows dose escalation of 186relabeled chimeric monoclonal antibody U36 radioimmunotherapy in a phase I dose escalation study",
abstract = "Purpose: In an earlier Phase I radioimmunotherapy (RIT) study with rhenium-186-labeled chimeric monoclonal antibody (cMAb) U36 in patients with refractory head and neck squamous cell carcinoma, the maximum tolerated activity was established at 1.0 GBq/m2, at which bone marrow doses ranged from 0.7 to 1.1 Gy. In the present study, further dose escalation in RIT was evaluated using a facile method of reinfusion of granulocyte colony-stimulating factor (G-CSF)-stimulated unprocessed whole blood. Experimental Design: Nine patients with recurrent or metastatic head and neck squamous cell carcinoma were treated at radiation dose levels of 1.0, 1.5, and 2.0 GBq/m2. Before RIT, G-CSF (10 μg/kg/day) was administered s.c. at home during 5 days. On day 6, just before administration of 186Relabeled cMAb U36, 1 liter of whole blood was harvested and kept unprocessed at 4°C until reinfusion after 72 h. Blood samples were taken for analysis of pharmacokinetics and bone marrow dosimetry. Patients were evaluated for myelotoxicity and tumor response. Results: Blood harvesting, RIT, and reinfusion of whole blood were well tolerated by all patients. G-CSF stimulation resulted in a mean of 0.41 × 106 CD34+ cells/kg (range, 0.15-0.83 × 106 CD34+ cells/kg) and a mean committed colony-forming units granulocyte macrophage count of 5.62 × 104/kg (range, 0.62-13.37 × 104/kg). The mean biological half-life of 186Relabeled cMAb U36 in blood was 72.6 ± 16.0 h, and bone marrow doses ranged from 2.1 to 2.8 Gy at the highest dose level. Myelotoxicity exceeding grade 3 was not observed. Stable disease was observed in five of nine patients, ranging from 3 to 5 months, and was still ongoing in one of these patients. Conclusions: This study indicates that a doubling of the maximum tolerated activity and bone marrow dose of 186Relabeled cMAb U36 can be achieved using reinfusion of GCSF-stimulated unprocessed whole blood.",
author = "Colnot, {David R.} and Ossenkoppele, {Gert J.} and Roos, {Jan C.} and Quak, {Jasper J.} and {De Bree}, Remco and B{\"o}rjesson, {Pontus K.} and Huijgens, {Peter C.} and Snow, {Gordon B.} and {Van Dongen}, {Guus A M S}",
year = "2002",
month = "11",
day = "1",
language = "English",
volume = "8",
pages = "3401--3406",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Reinfusion of unprocessed, granulocyte colony-stimulating factor-stimulated whole blood allows dose escalation of 186relabeled chimeric monoclonal antibody U36 radioimmunotherapy in a phase I dose escalation study

AU - Colnot, David R.

AU - Ossenkoppele, Gert J.

AU - Roos, Jan C.

AU - Quak, Jasper J.

AU - De Bree, Remco

AU - Börjesson, Pontus K.

AU - Huijgens, Peter C.

AU - Snow, Gordon B.

AU - Van Dongen, Guus A M S

PY - 2002/11/1

Y1 - 2002/11/1

N2 - Purpose: In an earlier Phase I radioimmunotherapy (RIT) study with rhenium-186-labeled chimeric monoclonal antibody (cMAb) U36 in patients with refractory head and neck squamous cell carcinoma, the maximum tolerated activity was established at 1.0 GBq/m2, at which bone marrow doses ranged from 0.7 to 1.1 Gy. In the present study, further dose escalation in RIT was evaluated using a facile method of reinfusion of granulocyte colony-stimulating factor (G-CSF)-stimulated unprocessed whole blood. Experimental Design: Nine patients with recurrent or metastatic head and neck squamous cell carcinoma were treated at radiation dose levels of 1.0, 1.5, and 2.0 GBq/m2. Before RIT, G-CSF (10 μg/kg/day) was administered s.c. at home during 5 days. On day 6, just before administration of 186Relabeled cMAb U36, 1 liter of whole blood was harvested and kept unprocessed at 4°C until reinfusion after 72 h. Blood samples were taken for analysis of pharmacokinetics and bone marrow dosimetry. Patients were evaluated for myelotoxicity and tumor response. Results: Blood harvesting, RIT, and reinfusion of whole blood were well tolerated by all patients. G-CSF stimulation resulted in a mean of 0.41 × 106 CD34+ cells/kg (range, 0.15-0.83 × 106 CD34+ cells/kg) and a mean committed colony-forming units granulocyte macrophage count of 5.62 × 104/kg (range, 0.62-13.37 × 104/kg). The mean biological half-life of 186Relabeled cMAb U36 in blood was 72.6 ± 16.0 h, and bone marrow doses ranged from 2.1 to 2.8 Gy at the highest dose level. Myelotoxicity exceeding grade 3 was not observed. Stable disease was observed in five of nine patients, ranging from 3 to 5 months, and was still ongoing in one of these patients. Conclusions: This study indicates that a doubling of the maximum tolerated activity and bone marrow dose of 186Relabeled cMAb U36 can be achieved using reinfusion of GCSF-stimulated unprocessed whole blood.

AB - Purpose: In an earlier Phase I radioimmunotherapy (RIT) study with rhenium-186-labeled chimeric monoclonal antibody (cMAb) U36 in patients with refractory head and neck squamous cell carcinoma, the maximum tolerated activity was established at 1.0 GBq/m2, at which bone marrow doses ranged from 0.7 to 1.1 Gy. In the present study, further dose escalation in RIT was evaluated using a facile method of reinfusion of granulocyte colony-stimulating factor (G-CSF)-stimulated unprocessed whole blood. Experimental Design: Nine patients with recurrent or metastatic head and neck squamous cell carcinoma were treated at radiation dose levels of 1.0, 1.5, and 2.0 GBq/m2. Before RIT, G-CSF (10 μg/kg/day) was administered s.c. at home during 5 days. On day 6, just before administration of 186Relabeled cMAb U36, 1 liter of whole blood was harvested and kept unprocessed at 4°C until reinfusion after 72 h. Blood samples were taken for analysis of pharmacokinetics and bone marrow dosimetry. Patients were evaluated for myelotoxicity and tumor response. Results: Blood harvesting, RIT, and reinfusion of whole blood were well tolerated by all patients. G-CSF stimulation resulted in a mean of 0.41 × 106 CD34+ cells/kg (range, 0.15-0.83 × 106 CD34+ cells/kg) and a mean committed colony-forming units granulocyte macrophage count of 5.62 × 104/kg (range, 0.62-13.37 × 104/kg). The mean biological half-life of 186Relabeled cMAb U36 in blood was 72.6 ± 16.0 h, and bone marrow doses ranged from 2.1 to 2.8 Gy at the highest dose level. Myelotoxicity exceeding grade 3 was not observed. Stable disease was observed in five of nine patients, ranging from 3 to 5 months, and was still ongoing in one of these patients. Conclusions: This study indicates that a doubling of the maximum tolerated activity and bone marrow dose of 186Relabeled cMAb U36 can be achieved using reinfusion of GCSF-stimulated unprocessed whole blood.

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M3 - Article

VL - 8

SP - 3401

EP - 3406

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 11

ER -