Table 3. Studies of NDV-Infected Tumor Cell Vaccines in Which Therapeutic Benefit Was Assesseda continued...
Infection of Patients With NDV (Including Strain MTH-68)
The following information is summarized in a table located at the end of this section.
To date, most research into the treatment of human cancer by infection of patients with NDV has been conducted in Hungary.[38,39,41,42] Reviewed in [14,49,50,51] The Hungarian research effort has been led by a single group of investigators who advocate the use of NDV strain MTH-68, which is presumed to be lytic. Findings from these investigations have been published in the form of an anecdotal report that briefly describes results for 3 patients who had metastatic disease; a single case report about a child who had glioblastoma multiforme; a report of a small case series that included 4 individuals with advanced cancer; and a report of a placebo-controlled, phase II clinical trial that included 33 patients in the NDV treatment group and 26 patients in the placebo group. The patients in the phase II trial had various advanced cancers. According to the investigators, MTH-68 treatment was beneficial for the majority of these patients.
The five patients described in the case report and the small case series were reported to have had either a complete remission or a partial remission following NDV therapy.[38,42] Two of the patients in the case series had advanced colorectal cancer, another had melanoma, and the fourth had advanced Hodgkin disease. These five patients were treated with NDV daily for periods of time that ranged from 1 month to 7 years. Inhalation and intravenous injection were the main routes of virus administration. One of the patients with colorectal cancer, however, was treated by means of intracolonic injection (i.e., via a colostomy opening) for 4 weeks. It is important to note that all five patients were treated with conventional therapy before the start of NDV therapy and that four of the five received conventional therapy either concurrently with NDV therapy or after it. Given the small number of patients, the absence of control subjects, and the overlapping treatments, it is difficult to draw conclusions about the effectiveness of NDV therapy from these small studies. Nonetheless, taken as a whole the results of the available NDV studies suggest potential clinical value warranting further study with controlled clinical trials.
In the phase II trial, NDV was administered by inhalation only 2 times a week for a period of 6 months. The 33 patients in the NDV treatment group had the following types of cancer: colorectal (n = 13), stomach (n = 6), kidney (n = 3), pancreatic (n = 3), lung (n = 1), breast (n = 1), ovarian (n = 1), melanoma (n = 1), bile duct (n = 1), gallbladder (n = 1), sarcoma (n = 1), and ependymoma (n = 1). The distribution of cancers among the 26 patients in the placebo group was as follows: colorectal (n = 5), stomach (n = 3), kidney (n = 6), lung (n = 1), breast (n = 1), melanoma (n = 7), bile duct (n = 1), sarcoma (n = 1), and bladder (n = 1). Twenty-four (73%) of the patients in the NDV treatment group had distant metastases when they were recruited into the trial, compared with 22 (85%) of the patients in the placebo group. Thirty-one (94%) of the patients in the NDV treatment group received some form of conventional therapy (surgery, chemotherapy, or radiation therapy) before the start of virus therapy; 9 (29%) of these patients were treated with more than one type of conventional therapy. All (100%) of the patients in the placebo group received conventional therapy before the start of virus therapy; 15 (58%) of these individuals were treated with more than one type of conventional therapy. The average age of the patients in the NDV treatment group was 62.6 years, compared with an average age of 55.4 years for the patients in the placebo group. The two groups, however, were well-balanced with respect to gender distribution (61% males and 39% females in each treatment group) and average performance status (1.39 for each group, based on the following scale: 0 = free from complaints, 1 = capable of easy work, 2 = less than 50% bed rest required, 3 = more than 50% bed rest required, 4 = 100% bedridden). Two complete responses and six partial responses were reported for patients in the NDV treatment group, whereas no responses were observed in the placebo group. In the NDV treatment group, ten patients were reported to have stable disease, compared with just two patients in the placebo group. In addition, more patients in the NDV treatment group than in the placebo group reported subjective improvements in their quality of life. Twenty-two (67%) of the patients in the NDV treatment group survived at least 1 year, compared with 4 (15%) of the patients in the placebo group. The 2-year survival proportions were 21% and 0% for patients in the NDV treatment group and the placebo group, respectively.