Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide
Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide
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DOI：
10.1097/00002371-199607000-00006
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发表时间：
1996-07-01
影响因子：
3.9
通讯作者：
Longenecker, BM
中科院分区：
文献类型：
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作者：
MacLean, GD;Miles, DW;Longenecker, BM
THERATOPE（Biomira Inc.，埃德蒙顿，AB，加拿大）STn-KLH癌症疫苗诱导针对合成STn表位和针对表达STn样表位的天然粘蛋白OSM的强抗体滴度。在两个癌症中心接受治疗的转移性乳腺癌患者中开展的前瞻性随机研究中，比较了不同低剂量免疫调节性环磷酰胺（周期）预治疗对THERATOPE STn-KLH缓解的影响。在THERATOPE治疗前，患者随机接受静脉周期300 mg/m2（第-3天）或口服周期50 mg（第-14天至第-3天（含））或无周期。在THERATOPE之前接受周期静脉注射的患者中，抗STn和抗OSM抗体滴度更高。接受周期静脉注射和THERATOPE STn-KLH癌症疫苗治疗的患者的生存时间显著长于接受相同STn疫苗口服或无周期治疗的患者（预计中位生存期为19.7个月，实际中位生存期为12.6个月，p = 0.0176）。虽然目前尚不清楚抗STn抗体应答如何改变肿瘤生物学，但我们注意到静脉给药周期组患者在9周时显示疾病进展的患者百分比较低，并且血清抗STn抗体滴度与可测量肿瘤生长之间呈负相关。肿瘤生长与抗KLH抗体滴度之间无相关性。这些数据与THERATOPE STn-KLH癌症疫苗的治疗效果一致，并支持开展III期研究以进一步探索这一点。
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 (cycle) pretreatments on the response to THERATOPE STn-KLH was compared. Patients were randomized to receive either intravenous cycle 300 mg/m(2) on day -3, or oral cycle 50 mg daily from days -14 to -3 inclusive, or no cycle, before THERATOPE treatments. The anti-STn and anti-OSM antibody titers were higher in the 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 treated 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 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.