ENHANCING THE EFFECT OF THERATOPE STN-KLH CANCER VACCINE IN PATIENTS WITH METASTATIC BREAST-CANCER BY PRETREATMENT WITH LOW-DOSE INTRAVENOUS CYCLOPHOSPHAMIDE

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. I n prospective, randomized studies in patients with metastatic breast c ancer treated at two cancer centers, the effect of different low-dose, immunomodulatory cyclophosphamide (cycle) pretreatments on the respon se to THERATOPE STn-KLH was compared. Patients were randomized to rece ive either intravenous cycle 300 mg/m(2) on day -3, or oral cycle 50 m g daily from days -14 to -3 inclusive, or no cycle, before THERATOPE t reatments. The anti-STn and anti-OSM antibody titers were higher in th e patients who received cycle intravenously before THERATOPE, Patients treated with cycle 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 t reated with the same STn vaccine with oral or no cycle. Although it is not clear how the anti-STn antibody response modifies tumor biology, we noted that patients in the intravenously administered cycle group h ad a lower percentage of patients showing progressive disease at 9 wee ks, and that there was an inverse correlation between serum anti-STN a ntibody titer and growth of measurable tumors. There was no correlatio n between tumor growth and anti-KLH antibody titers. These data are co nsistent with a therapeutic effect of THERATOPE STn-KLH cancer vaccine and support development of a phase III study to explore this further.