Human / Clinical Studies
The fourth U.S. study of NDV oncolysates in patients with melanoma was also a phase II trial. This trial, which was conducted by a different group of researchers, involved 24 patients who likewise had disease that had spread to regional lymph nodes. The patients in this trial were treated in a manner similar to that of the patients in the other two phase II trials. In this trial, however, only 37% of the patients remained disease free 5 years after surgery; this disease-free survival percentage did not differ substantially from the 30% disease-free survival estimated for a group of historical control subjects who had been treated at the same institution with surgery alone or surgery and another type of adjuvant therapy.
In contrast to the evidence of benefit found in the other phase II trials, the absence of benefit for NDV oncolysates in this fourth clinical trial remains to be explained. It has been reported that different methods of oncolysate preparation were used by the two groups of investigators who conducted these studies. The positive results obtained by the first research group, however, must be viewed with caution. Until these results are confirmed independently in larger, randomized clinical trials, they should be considered preliminary.
Two additional phase II studies of NDV oncolysates have been conducted in Germany. One study involved 208 patients with locally advanced renal cell carcinoma (i.e., large tumors and no regional lymph node metastasis or tumors of any size and 1 or 2 regional lymph nodes positive for cancer).[8,12] The second study involved 22 patients with either metastatic breast cancer or metastatic ovarian cancer.[5,7]
In the advanced renal cell carcinoma study,[8,12] strain 73-T was used to prepare autologous oncolysates that were given to patients by subcutaneous injection once a week for 8 to 10 weeks beginning 1 to 3 months after radical surgery (i.e., nephrectomy and regional lymph node dissection). Two cytokines, low-dose recombinant interleukin-2 and recombinant interferon -alpha, were added to the oncolysate vaccines. Among the 208 patients who entered this study, 203 were followed for a period of time that ranged from 6 months to 64 months from the date of surgery, and these patients were considered evaluable for response. Approximately 91% of the evaluable patients remained free of detectable cancer during follow-up; 9% showed signs of progressive disease. The median time to relapse was more than 21 months. Fifty-six of the evaluable patients had 23 months to 64 months of follow-up from the time of surgery, and approximately 18% of these individuals showed signs of progressive disease during follow-up. All relapses in this subset of 56 patients occurred within 34 months of surgery.