"Multi-enzyme-targeted" immunochemotherapy: a salvage therapy protocol.

Human tumor cells have markedly elevated activity of enzymes of the purine and pyrimidine de novo and salvage pathways. Our therapy protocol is based on these findings. Different antimetabolites (MTX, 5-FU, dFdC, AZT) were administered to hit key enzymes. Vindesine and ifosfamide were aimed to block macromolecules. Repair mechanisms were impaired by hydroxyurea and topotecan. DNA transcription was blocked by actinomycin. IFNs (alpha, gamma) and IL-2 served as immuno-modulators. 47 patients (age 61.5 years, Karnowsky score 85%) were treated in an out-patient-setting. Median number of cycles was 3. General toxicity was low. Leucocytes, platelets, and monocytes were significantly reduced during therapy, but returned to normal on day 29. Lymphocyte subtypes did not show significant changes. 3 complete clinical responses, 22 partial responses, 9 progressive diseases were observed. CR occurred in 1/4 patients with kidney, in 1/1 with bladder, and in 1/5 with breast cancer.