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.
UR - http://www.scopus.com/inward/record.url?scp=0036845695&partnerID=8YFLogxK
M3 - Article
C2 - 12429627
AN - SCOPUS:0036845695
SN - 1078-0432
VL - 8
SP - 3401
EP - 3406
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -