Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer.
The safety, pharmacokinetics, biodistribution and radiation dosimetry of (111)In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, were evaluated in a first-in-human trial. Dose escalation was performed in patients with EGFR-positive metastatic breast cancer who had received ≥2 prior course...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
e-Century Publishing
2014
|
| _version_ | 1797066700401672192 |
|---|---|
| author | Vallis, K Reilly, R Scollard, D Merante, P Brade, A Velauthapillai, S Caldwell, C Chan, I Freeman, M Lockwood, G Miller, N Cornelissen, B Petronis, J Sabate, K |
| author_facet | Vallis, K Reilly, R Scollard, D Merante, P Brade, A Velauthapillai, S Caldwell, C Chan, I Freeman, M Lockwood, G Miller, N Cornelissen, B Petronis, J Sabate, K |
| author_sort | Vallis, K |
| collection | OXFORD |
| description | The safety, pharmacokinetics, biodistribution and radiation dosimetry of (111)In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, were evaluated in a first-in-human trial. Dose escalation was performed in patients with EGFR-positive metastatic breast cancer who had received ≥2 prior courses of systemic treatment. (111)In-DTPA-hEGF (0.25 mg) was administered once intravenously (i.v.). Blood was collected for biochemistry/hematology testing and pharmacokinetic and immunogenicity analyses at selected times post injection (p.i.). Whole body planar images were acquired at 1, 4-6, 24 and 72 h p.i. and SPECT images at 24 and/or 72 h p.i. Macrodosimetry (MIRD) for the whole body and organs was estimated using OLINDA. Correlative radiological imaging was obtained at baseline, 1 and 3 months and then 6 monthly. Toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE)v2.0. Sixteen patients, median age 47 yr (range, 35-59), received (111)In-DTPA-hEGF as follows: 357-434 MBq (7), 754-805 MBq (3), 1,241-1,527 MBq (3) and 2,030-2,290 MBq (3). Fifteen were evaluable for toxicity. The commonest adverse events (AE) were flushing, chills, nausea, and vomiting occurring during or immediately p.i. One patient experienced Grade 3 thrombocytopenia (attributed to bone marrow infiltration by cancer). There were no other Grade 3 or 4 AEs. Maximum tolerated dose was not reached. Clear accumulation of radiopharmaceutical in at least one known site of disease was observed in 47% of patients. (111)In-DTPA-hEGF was cleared biexponentially from the blood with α-phase T½ of 0.16 ± 0.03 h and β-phase T½ of 9.41 ± 1.93 h. (111)In-DTPA-hEGF was not immunogenic. The mean radiation dose estimates in mGy/MBq for whole body, liver, kidneys, spleen and thyroid were 0.08, 0.86, 0.74, 0.37 and 0.30, respectively. No objective antitumor responses were observed at the doses studied. In summary, administered amounts of up to 2,290 MBq (0.25 mg) of (111)In-DTPA-hEGF were well tolerated as a single i.v. injection. |
| first_indexed | 2024-03-06T21:45:46Z |
| format | Journal article |
| id | oxford-uuid:4986bf52-656e-48f9-83ff-f4a6e4d59e72 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:45:46Z |
| publishDate | 2014 |
| publisher | e-Century Publishing |
| record_format | dspace |
| spelling | oxford-uuid:4986bf52-656e-48f9-83ff-f4a6e4d59e722022-03-26T15:32:11ZPhase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4986bf52-656e-48f9-83ff-f4a6e4d59e72EnglishSymplectic Elements at Oxforde-Century Publishing2014Vallis, KReilly, RScollard, DMerante, PBrade, AVelauthapillai, SCaldwell, CChan, IFreeman, MLockwood, GMiller, NCornelissen, BPetronis, JSabate, KThe safety, pharmacokinetics, biodistribution and radiation dosimetry of (111)In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, were evaluated in a first-in-human trial. Dose escalation was performed in patients with EGFR-positive metastatic breast cancer who had received ≥2 prior courses of systemic treatment. (111)In-DTPA-hEGF (0.25 mg) was administered once intravenously (i.v.). Blood was collected for biochemistry/hematology testing and pharmacokinetic and immunogenicity analyses at selected times post injection (p.i.). Whole body planar images were acquired at 1, 4-6, 24 and 72 h p.i. and SPECT images at 24 and/or 72 h p.i. Macrodosimetry (MIRD) for the whole body and organs was estimated using OLINDA. Correlative radiological imaging was obtained at baseline, 1 and 3 months and then 6 monthly. Toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE)v2.0. Sixteen patients, median age 47 yr (range, 35-59), received (111)In-DTPA-hEGF as follows: 357-434 MBq (7), 754-805 MBq (3), 1,241-1,527 MBq (3) and 2,030-2,290 MBq (3). Fifteen were evaluable for toxicity. The commonest adverse events (AE) were flushing, chills, nausea, and vomiting occurring during or immediately p.i. One patient experienced Grade 3 thrombocytopenia (attributed to bone marrow infiltration by cancer). There were no other Grade 3 or 4 AEs. Maximum tolerated dose was not reached. Clear accumulation of radiopharmaceutical in at least one known site of disease was observed in 47% of patients. (111)In-DTPA-hEGF was cleared biexponentially from the blood with α-phase T½ of 0.16 ± 0.03 h and β-phase T½ of 9.41 ± 1.93 h. (111)In-DTPA-hEGF was not immunogenic. The mean radiation dose estimates in mGy/MBq for whole body, liver, kidneys, spleen and thyroid were 0.08, 0.86, 0.74, 0.37 and 0.30, respectively. No objective antitumor responses were observed at the doses studied. In summary, administered amounts of up to 2,290 MBq (0.25 mg) of (111)In-DTPA-hEGF were well tolerated as a single i.v. injection. |
| spellingShingle | Vallis, K Reilly, R Scollard, D Merante, P Brade, A Velauthapillai, S Caldwell, C Chan, I Freeman, M Lockwood, G Miller, N Cornelissen, B Petronis, J Sabate, K Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer. |
| title | Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer. |
| title_full | Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer. |
| title_fullStr | Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer. |
| title_full_unstemmed | Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer. |
| title_short | Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer. |
| title_sort | phase i trial to evaluate the tumor and normal tissue uptake radiation dosimetry and safety of 111 in dtpa human epidermal growth factor in patients with metastatic egfr positive breast cancer |
| work_keys_str_mv | AT vallisk phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT reillyr phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT scollardd phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT merantep phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT bradea phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT velauthapillais phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT caldwellc phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT chani phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT freemanm phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT lockwoodg phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT millern phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT cornelissenb phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT petronisj phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer AT sabatek phaseitrialtoevaluatethetumorandnormaltissueuptakeradiationdosimetryandsafetyof111indtpahumanepidermalgrowthfactorinpatientswithmetastaticegfrpositivebreastcancer |