Human / Clinical Studies
The two phase II trials looked for evidence of therapeutic benefit in patients who had either metastatic colorectal carcinoma [15,22] or locally advanced colorectal carcinoma. The trial that involved patients with metastatic disease recruited 23 individuals whose colorectal cancer had recurred in the liver following treatment of their primary tumor or whose colorectal cancer and liver metastases were diagnosed at the same time.[15,22] After surgery to remove the primary tumor and/or the metastases, all patients appeared to be free of residual cancer. NDV-infected, autologous tumor cells were then administered by intradermal injection every 2 weeks beginning 2 weeks after surgery. The total number of vaccinations given to the patients in this trial, however, is not clear. One of the two trial reports indicates that each patient received four vaccinations and a booster, which was given approximately 23 weeks after surgery. The second trial report  indicates that each patient received five vaccinations and a booster. No additional treatment (chemotherapy or radiation therapy) was allowed during the trial.
During 18 months of follow-up, 14 (61%) of the patients in this trial had relapses of their cancer, compared with relapses in 20 (87%) of 23 historical control subjects who were treated with surgery alone by the same surgeons at the same hospital. Although this difference in disease-free survival was statistically significant, there was no statistically significant difference in overall survival between the study subjects and the historical control subjects. The researchers also reported that, in general, the patients who had the strongest immune system responses against uninfected autologous tumor cells after vaccination had the longest disease-free survival times. It should be noted, however, that the reporting of patient responses against uninfected autologous tumor cells in this trial was inconsistent.[15,22] One trial report, which described results after 12 months of follow-up, indicates that 11 of 23 patients showed increased immune system reactivity against uninfected autologous tumor cells during the vaccination program; whereas the second trial report, which described results after 18 months of follow-up, indicates that only 9 of 23 patients showed increased reactivity against uninfected autologous tumor cells.
The phase II trial that involved patients with locally advanced colorectal carcinoma (i.e., large tumors and no regional lymph node metastasis or tumors of any size and regional lymph nodes that were positive for cancer) recruited 57 individuals. Among these 57 patients, 48 were treated with NDV-infected, whole cell vaccines, and 9 were treated with vaccines composed of autologous tumor cells and the bacteriumBacillus Calmette Guerin (BCG), which also has been used as an immune system stimulator. Patients recruited for this trial were treated first with surgery and then were given a choice between participating in the trial or receiving chemotherapy. The individuals who chose to participate in the trial were injected intradermally with the appropriate autologous tumor cell vaccines every other week for a total of 6 weeks (i.e., 3 vaccinations per patient) beginning 6 to 8 weeks after surgery. The follow-up period ranged from 6 months to 43 months (median of 22 months), and disease-free survival and overall survival were estimated for the vaccinated patients and for 661 historical control subjects who were treated with surgery alone. Two years after surgery, overall survival for the patients who were treated with NDV-infected, autologous whole cell vaccines was 98%, compared with 67% overall survival for the patients who were treated with BCG tumor cell vaccines and 74% overall survival for the historical control subjects. The differences in survival between the NDV/tumor-cell-vaccinated group and the other two groups were statistically significant. Disease-free survival 2 years after surgery for the NDV/tumor-cell-treated patients was 72%. The researchers who conducted this trial also reported that overall survival for the NDV/tumor-cell-treated group was comparable to that of the group of patients (n = 15) who chose to be treated with chemotherapy rather than immunotherapy.