Human / Clinical Studies
The same research group conducted a parallel investigation in which immune system responses to combination oncolysate and cytokine therapy were measured in 38 patients who had advanced renal cell carcinoma. In this parallel study, responses to NDV antigens (i.e., the production of anti-NDV antibodies) and transient increases in blood levels of the cytokines interferon-alpha, interferon-gamma, and tumor necrosis factor (TNF)-alpha were found, but responses thought to be important to effective antitumor immunity (i.e., the production of antibodies against tumor-specific antigens, increases in natural killer (NK) cell activity, and increases in blood levels of helper T cells [i.e., CD4 antigen-positive cells] and cytotoxic T cells [i.e., CD8 antigen-positive cells]) were not.
The phase II study of NDV oncolysates in patients with metastatic breast or metastatic ovarian cancer was described by its investigators as a study of autologous, whole cell vaccines.[5,7] The lytic strain Italien, however, was used in this study, so it is likely that immune system responses in the treated patients were stimulated by cellular fragments rather than by intact cancer cells.
In the study, 22 patients were vaccinated by intradermal injection at least 3 times during a 6- to 8-week period that began 2 weeks after surgery to remove malignant cells (either primary tumor cells or metastatic tumor cells). The patients also received intravenous injections of cyclophosphamide, high-dose recombinant interleukin-2, and autologous lymphocytes that had been simulated in vitro by treatment with interleukin-2. The cyclophosphamide was administered to block the activity of a class of T cells (i.e., suppressor T cells) that might weaken the desired immune responses. On average, the patients were followed for a period of 23 months from the time of surgery. Nine patients were reported to have either a complete response or a partial response after vaccine therapy. Five patients had stable disease, and eight had progressive disease. The average duration of response was 5 months, after which disease progression was again observed. Blood samples taken from the patients during therapy showed increases in the numbers of NK cells and increases in serum concentrations of the cytokines interferon-alpha and TNF-alpha, but these changes did not persist. No other immune system responses were detected. Because this was an uncontrolled study, it is unclear whether any of the observed clinical and/or immune system responses can be attributed to treatment with NDV oncolysates. Furthermore, because the lytic strain Italien was used in the study, the possibility that the observed tumor regressions were due, in part, to oncolysis cannot be ruled out.
Table 2. Studies of NDV Oncolysates in Which Therapeutic Benefit Was Assesseda,b
No. = number.
a See text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
b Oncolysates are prepared from virus-infected cancer cells; they consist primarily of cell membrane fragments and contain virus proteins and cancer cell proteins.
c Number of patients treated plus number of patients control may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were given the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
d The strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.
e Chemotherapy, radiation therapy, hormonal therapy, or cytokine therapy given/allowed at the same time as oncolysate treatment.
f For information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.
|Reference Citation(s)||Type of Study||Type of Cancer ||No. of Patients: Enrolled; Treated; Controlc||Strongest Benefit Reportedd||Concurrent Therapye||Level of Evidence Scoref|
|[1,2,4,11]||Phase II trial||Advanced melanoma||32; 32; Historical controls ||Improved overall survival||No ||3iiA |
|[1,2,11]||Phase II trial||Advanced melanoma||51; 51; Historical controls ||Improved overall survival||No ||3iiA |
|||Phase II trial||Advanced melanoma||24; 24; Historical controls ||None||No||3iiDi |
|[5,7]||Phase II trial||Metastatic breast or ovarian ||22; 22; None ||Complete/partial tumor response, 9 patients||Yes||3iiDiii |
|[8,12]||Phase II trial||Advanced renal cell ||208; 203; Historical controls ||Improved disease-free survival ||Yes||3iiiDi |
|[9,10]||Phase I trial ||Advanced melanoma||13; 13; None ||Complete tumor response, 1 patient||Yes||3iiiDii |