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Vallis KA, Reilly RM, Scollard D, et al. 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. Am J Nucl Med Mol Imaging. 2014;4(2):181-92
Vallis, K. A., Reilly, R. M., Scollard, D., Merante, P., Brade, A., Velauthapillai, S., Caldwell, C., Chan, I., Freeman, M., Lockwood, G., Miller, N. A., Cornelissen, B., Petronis, J., & Sabate, K. (2014). 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. American journal of nuclear medicine and molecular imaging, 4(2), 181-92.
Vallis, Katherine A, et al. "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." American journal of nuclear medicine and molecular imaging vol. 4,2 (2014): 181-92.
Vallis KA, Reilly RM, Scollard D, Merante P, Brade A, Velauthapillai S, Caldwell C, Chan I, Freeman M, Lockwood G, Miller NA, 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. Am J Nucl Med Mol Imaging. 2014 Mar 20;4(2):181-92. eCollection 2014. PMID: 24753984; PMCID: PMC3992211.
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Am J Nucl Med Mol Imaging. 2014 Mar 20;4(2):181-92. eCollection 2014.

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.

American journal of nuclear medicine and molecular imaging

Katherine A Vallis, Raymond M Reilly, Deborah Scollard, Pat Merante, Anthony Brade, Sobi Velauthapillai, Curtis Caldwell, Ida Chan, Marc Freeman, Gina Lockwood, Naomi A Miller, Bart Cornelissen, Jennifer Petronis, Kathryn Sabate

Affiliations

  1. Gray Institute for Radiation Oncology and Biology, University of Oxford Oxford, UK.
  2. Leslie Dan Faculty of Pharmacy, University of Toronto Toronto, Canada ; Toronto General Hospital Research Institute Toronto, Canada ; Medical Imaging, University of Toronto Toronto, Canada.
  3. Leslie Dan Faculty of Pharmacy, University of Toronto Toronto, Canada.
  4. Radiation Medicine Program, Princess Margaret Hospital, University of Toronto Canada.
  5. Medical Imaging, University of Toronto Toronto, Canada ; Medical Physics, Sunnybrook Health Sciences Center Toronto, Canada.
  6. Medical Imaging, University of Toronto Toronto, Canada.
  7. Biostatistics, Princess Margaret Hospital Toronto, Canada.
  8. Pathology, University Health Network Toronto, Canada.
  9. Medical Oncology and Hematology, Princess Margaret Hospital Toronto, Canada.

PMID: 24753984 PMCID: PMC3992211

Abstract

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.

Keywords: 111In-DTPA-hEGF; Auger electron; Phase I trial; breast cancer

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