A fifth phase II clinical trial tested NDV-infected, autologous tumor cell vaccines in 43 patients who had various advanced cancers (16 ovarian, 22 breast, 1 cervical, 1 vaginal, 1 lung, and 1 chondrosarcoma) that had not responded to previous treatment. The patients in this trial received intravenous injections of cyclophosphamide and epirubicin, subcutaneous injections of low-dose recombinant interleukin-2 and interferon-alpha, and intradermal injections of the tumor cell vaccines. The cyclophosphamide and epirubicin were administered to block the activity of suppressor T cells that might weaken the desired immune responses. The trial report provided no information about the treatments that had failed, the time intervals between the failure of the last treatment and the beginning of immunotherapy, or how many vaccinations each patient received. The researchers considered 31 of the 43 patients to be evaluable for response. Among the evaluable patients, one individual who had ovarian cancer had a complete response that lasted more than 2 months. The remaining evaluable patients had either partial responses (n = 11), stable disease (n = 10), or progressive disease (n = 9) following treatment. In view of the limited information given, no conclusions can be drawn from this uncontrolled study about the effectiveness of NDV-infected, autologous whole cell vaccines in this patient population.
One additional clinical study evaluated the effect of vaccine quality on the survival of patients who were treated with NDV-infected, autologous tumor cells. In this retrospective study, survival was estimated separately for three groups of patients who had early breast cancer (n = 63), metastatic breast cancer (n = 27), or metastatic ovarian cancer (n = 31) and who had sufficient numbers of recovered tumor cells to allow at least two vaccinations. Most of the patients who had early breast cancer were treated after surgery with conventional adjuvant therapies (chemotherapy, radiation therapy, and/or hormonal therapy) in addition to vaccine therapy. The patients who had metastatic breast or ovarian cancer had failed to respond to conventional treatments before the start of vaccine therapy. In addition to receiving tumor cell vaccines, these latter patients were treated with oral indomethacin and cimetidine, intravenous cyclophosphamide and epirubicin, and subcutaneous low-dose recombinant interleukin-2 and interferon-alpha. The indomethacin, cimetidine, cyclophosphamide, and epirubicin were given in an attempt to prevent the suppression of desired immune system responses. The autologous vaccines were classified as either high quality or low quality on the basis of the following two parameters: the ratio of tumor cells to other types of cells and the percentage of live tumor cells. The median times from surgery to the start of immunotherapy were 13 days, 27 days, and 28 days for the patients who had early breast cancer, metastatic breast cancer, and metastatic ovarian cancer, respectively.
Overall survival 4 years after surgery was estimated to be 96% for the patients with early breast cancer who had received a high-quality vaccine (n = 32), compared with an overall survival of 68% for those who had received a low-quality vaccine (n = 31). For the patients with metastatic breast cancer, the median survival time was estimated to be 1.75 years from the start of immunotherapy for those who had received a high-quality vaccine (n = 13), compared with a median survival time of 0.75 years for those who had received a low-quality vaccine (n = 14) (median follow-up time = 1.4 years). For patients with metastatic ovarian cancer, the median survival time was estimated to be 1.16 years from the start of immunotherapy for those who had received a high-quality vaccine (n = 18), compared with a median survival time of 0.84 years for those who had received a low-quality vaccine (n = 13) (median follow-up time = 1.23 years). The only survival difference that was statistically significant was the one for the patients who had early breast cancer. The retrospective nature of this study and the small numbers of patients in each treatment group should be viewed as major weaknesses.