Elizabeth A. Grosen

Hormone replacement therapy in breast cancer survivors: A cohort study ☆ ☆☆ ★

OBJECTIVE Our purpose was to measure any adverse effect (if one exists) of hormone replacement therapy administered to breast cancer survivors. STUDY DESIGN Forty-one patients from a group of 77 patients who received hormone replacement therapy after therapy for breast cancer were matched with 82 comparison patients not receiving hormone replacement therapy. Both groups were taken from the same population on the basis of cancer registry of the Cancer Surveillance Program of Orange County and were compared with regard to survival results. RESULTS An analysis of survival time and disease-free time revealed no statistically significant difference between the two groups. CONCLUSIONS No obvious adverse effect of hormone replacement therapy could be shown in this pilot study. A case is made for a prospective randomized trial.

Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer

OBJECTIVES The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS). METHODS This is a Phase II crossover trial of Vigil (1.0×107 cells/intradermal injection/month for 4 to 12 doses) in Stage III/IV ovarian cancer patients achieving cCR (normal imaging, CA-125≤35units/ml, physical exam, and no symptoms suggestive of the presence of active disease) following primary surgical debulking and carboplatin/paclitaxel adjuvant or neoadjuvant chemotherapy. Patients received Vigil or standard of care during the maintenance period. RESULTS Forty-two patients were entered into trial, 31 received Vigil and 11 received standard of care. No≥Grade 3 toxicity related to product was observed. A marked induction of circulating activated T-cell population was observed against individual, pre-processed autologous tumor in the Vigil arm as compared to pre-Vigil baseline using IFNγ ELISPOT response (30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134 spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement was improved (mean 826days/median 604days in the Vigil arm from mean 481days/median 377days in the control arm, p=0.033). CONCLUSION In conjunction with the demonstrated safety, the high rate of induction of T-cell activation and correlation with improvement in RFS justify further Phase II/III assessment of Vigil.

TNF, LT and IL-1 natural inhibitors (soluble receptors and receptor antagonists) in women with ovarian cancer

Cell mediated immunity (CMI) is an important element of host antitumor resistance mechanisms. Tumor necrosis factor (TNF), lymphotoxin (LT) and interleukin-1 (IL-1) are key cytokines used by host effector lymphoid cells to orchestrate recognition, tissue destructive and inflammatory phases of these important reactions [1–4]. These molecules have multiple effects on cells in vitro and tissues in vivo. Some of these effects which are important for tumor regression are: 1. Cytolysis of certain transformed cells 2. Destruction of tumor blood vessels 3. Upregulation of surface proteins making tumor cells more immunogenic 4. Induce, recruit and activate host lymphoid cells to express antitumor activity 5. Induce inflammation 6. Leukocytosis [1–4].