Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide

J Immunother Emphasis Tumor Immunol. 1996 Jul;19(4):309-16. doi: 10.1097/00002371-199607000-00006.


THERATOPE (Biomira Inc., Edmonton, AB, Canada) STn-KLH cancer vaccine induces strong antibody titers against both the synthetic STn epitope and against a natural mucin, OSM, which expresses STn-like epitopes. In prospective, randomized studies in patients with metastatic breast cancer treated at two cancer centers, the effect of different low-dose, immunomodulatory cyclophosphamide (cyclo) pretreatments on the response to THERATOPE STn-KLH was compared. Patients were randomized to receive either intravenous cyclo 300 mg/m2 on day -3, or oral cyclo 50 mg daily from days -14 to -3 inclusive, or no cyclo, before THERATOPE treatments. The anti-STn and anti-OSM antibody titers were higher in the patients who received cyclo intravenously before THERATOPE. Patients treated with cyclo intravenously and THERATOPE STn-KLH cancer vaccine lived significantly longer (projected median survival of 19.7 months versus actual median survival of 12.6 months, p = 0.0176) than those treated with the same STn vaccine with oral or no cyclo. Although it is not clear how the anti-STn antibody response modifies tumor biology, we noted that patients in the intravenously administered cyclo group had a lower percentage of patients showing progressive disease at 9 weeks, and that there was an inverse correlation between serum anti-STN antibody titer and growth of measurable tumors. There was no correlation between tumor growth and anti-KLH antibody titers. These data are consistent with a therapeutic effect of THERATOPE STn-KLH cancer vaccine and support development of a phase III study to explore this further.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / therapy
  • Administration, Oral
  • Adult
  • Aged
  • Antigens, Tumor-Associated, Carbohydrate / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / therapy*
  • Cancer Vaccines / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Hemocyanins / therapeutic use*
  • Humans
  • Injections, Intravenous
  • Middle Aged
  • Neoplasm Metastasis
  • Premedication*
  • Prognosis


  • Antigens, Tumor-Associated, Carbohydrate
  • Cancer Vaccines
  • sialosyl-Tn antigen
  • Cyclophosphamide
  • Hemocyanins
  • keyhole-limpet hemocyanin