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. 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.
MacLean
G D
GD
Department of Oncology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Miles
D W
DW
Rubens
R D
RD
Reddish
M A
MA
Longenecker
B M
BM
D000230:Adenocarcinoma / Q000628:therapy; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006433:Hemocyanins / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011292:Premedication; D011379:Prognosis
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; C055491:sialosyl-Tn antigen; D003520:Cyclophosphamide; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin