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Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence†‡
From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
Version of Record online: 25 AUG 2008
Published 2008 American Cancer Society
Volume 113, Issue 7, pages 1666–1675, 1 October 2008
How to Cite
Holmes, J. P., Gates, J. D., Benavides, L. C., Hueman, M. T., Carmichael, M. G., Patil, R., Craig, D., Mittendorf, E. A., Stojadinovic, A., Ponniah, S. and Peoples, G. E. (2008), Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence. Cancer, 113: 1666–1675. doi: 10.1002/cncr.23772
This article is a US Government work and, as such, is in the public domain in the United States of America.
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army, the Department of the Navy, or the Department of Defense.
- Issue online: 17 SEP 2008
- Version of Record online: 25 AUG 2008
- Manuscript Accepted: 1 MAY 2008
- Manuscript Revised: 24 APR 2008
- Manuscript Received: 4 MAR 2008
- United States Military Cancer Institute
- Department of Surgery
- Uniformed Services University of the Health Sciences
- Department of Clinical Investigation at Walter Reed Army Medical Center
- breast cancer;
E75, a HER-2/neu-derived peptide, was administered as a preventive vaccine with granulocyte-macrophage–colony-stimulating factor (GM-CSF) in disease-free lymph node-positive (NP) and lymph node-negative (NN) breast cancer (BCa) patients. The optimal biologic dose (OBD) was determined based on toxicity and immunologic response.
Patients were vaccinated over 6 months (3, 4, or 6 times) with different doses of E75 plus GM-CSF. Toxicities were graded per National Cancer Institute Common Terminology Criteria. GM-CSF was reduced for significant toxicity. Immunologic response was measured by delayed type hypersensitivity test (DTH), and E75-specific CD8+ T-cells were quantified with human leukocyte antigen-A2:immunoglobulin G dimer and flow cytometry.
Ninety-nine patients (48 NP and 51 NN) were vaccinated in 7 dose groups. The OBD was 1000 μg E75 plus 250 μg GM-CSF monthly × 6. The optimal dose group (ODG, n = 29) experienced similar toxicities to the suboptimal dose group (SDG, n = 70), which was comprised of the remaining 6 groups. The ODG demonstrated a trend toward an increase in the average postvaccine dimer (0.87 ± 0.10% vs 0.67 ± 0.05%; P = .07), a significantly larger DTH response (21.5 ± 2.5 mm vs 11.3 ± 1.3 mm; P = .0002), and a trend toward decreased recurrences (3.4% vs 12.9%; P = .27). Compared with the SDG, the ODG had larger tumors (percentage ≥T2: 55% vs 23%; P = .004), more positive lymph nodes (percentage NP: 76% vs 37%; P = .001), and higher grade tumors (percentage grade 3: 52% vs 30%; P = .07), but a shorter median follow-up time (20 months vs 32 months; P < .001).
Compared with suboptimally dosed patients, the optimally dosed E75 vaccine in disease-free BCa patients had similar toxicity but enhanced HER-2/neu-specific immunity that may lead to decreased recurrences with additional follow-up. Cancer 2008. Published 2008 by the American Cancer Society.