title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Ninety-nine patients (48 NP and 51 NN) were vaccinated in 7 dose groups. The OBD was 1000 microg E75 plus 250 microg GM-CSF monthly x 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 > or =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).
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Division of Hematology and Medical Oncology, Naval Medical Center San Diego, San Diego, California, USA.
authors: Jarrod P
authors: JP
authors: Holmes
authors: Jeremy D
authors: JD
authors: Gates
authors: Linda C
authors: LC
authors: Benavides
authors: Matthew T
authors: MT
authors: Hueman
authors: Mark G
authors: MG
authors: Carmichael
authors: Ritesh
authors: R
authors: Patil
authors: Dianna
authors: D
authors: Craig
authors: Elizabeth A
authors: EA
authors: Mittendorf
authors: Alexander
authors: A
authors: Stojadinovic
authors: Sathibalan
authors: S
authors: Ponniah
authors: George E
authors: GE
authors: Peoples
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019496:Cancer Vaccines; C474513:HER-2 peptide E75 (369-377), human; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor