Published in Cancer Detection and Prevention 1993; 17(6):619-627.

Attenuated Veterinary Virus Vaccine for the Treatment of Cancer

Laszlo K Csatary, M.D.,^a Sandor Eckhardt, M.D.,^b Istran Bukosza, M.D.,^c Ferenc Czegledi, M.D.,^b Csaba Fenyvesi, M.D.,^d Peter Gergely, M.D., Ph.D.,^e Bela Bodey, M.D., Ph.D.^f and Christine M. Csatary, M.D.^a

Address all correspondence to: Laszlo K. Csatary, M.D., 2100 S. Ocean Lane, Fort Lauderdale, FL 33316

ABSTRACT: Attenuated (nonpathogenic) avian viruses have been used as a form of nonspecific immunological treatment for advanced human cancer. For this study, we used Newcastle disease virus (NDV) vaccine MTH-68/N in an open phase II/B, placebo-controlled (26 patients), multicenter clinical trial for the treatment of 33 patients with advanced cancers. NDV (4000 U/day) or placebo was administered by inhalation twice weekly. During the 6-month trial, the size and presence of primary tumors and metastases were objectively monitored at five institutions by radiologists unaware of the type of treatment that was given. Regression of tumor(s) and/or metastases were observed in eight cases treated with virus (vs. none in the placebo group; p<0.01). Ten additional patients treated with NDV had no further progression of their tumor sizes, whereas tumor stabilization was noted in only two control patients. Objective, favorable responses (regressions plus stabilization) to virus therapy thus occurred in a total of 18 patients (55%) compared to 2 patients in the placebo group (8%; p<0.01). Two cases of complete remission were noted in the group treated with NDV. Patients receiving virus therapy had a higher rate of survival at 1 to 2 years. Of 33 patients receiving virus vaccine, 22 survived 1 year, compared to only 4 of 26 patients in the control group (p<0.02). After 2 years, all seven survivors in the study were in the virus therapy group. There were no 2-year survivors in the control group (p <0.0001). Among colorectal cancer patients with metastases only to the liver, seven of eight patients receiving NDV therapy survived 1 year, compared to only one of five in the control group (p <0.04). Weight gain occurred in 14 (42%) of the NDV-treated group compared to none of the placebo group (p<0.001). Furthermore, improvement of subjective parameters were reported by a significantly higher percentage of patients treated with virus than those treated with placebo (p <0.01). For example, pain decreased in 11 patients (33%) of the experimental group and in no patients of the control group (p<0.001). Furthermore, a feeling of increased well-being was noted by 15 (45%) in the virus-treated group but not in any of the control group (p<0.001). A plausible mechanism of the antitumor activity of attenuated virus vaccines like NDV MTH-68 may involve immunostimulation and/or the release of cytokines (e.g., interferons, tumor necrosis factor, interleukin-1). Release of such endogenous pyrogens was clearly stimulated by NDV in patients in this study because we observed fever in response to virus inhalation in ten patients (30%) and not in response to placebo. Based on our clinically favorable results, future clinical trials are planned to include a greater number of patients with laboratory assessment of their immune parameters and cytokine levels.

KEY WORDS: avian viruses, cancer, immunotherapy, interferencia, phase II study.

http://www.cancerprev.org/Journal/Issues/17/6/464