In multidrug-resistant metastatic breast cancer, methotrexate + insulin produced a significant antitumoral response that was not seen with either methotrexate or insulin used separately.

In vitro exposure of malignant prostate cell lines to ascorbic acid-menadione showed that tumor cells were killed through a mechanism named autoschizis. Experimental animal studies showed that autoschizis is also evident when ascorbic acid-menadione is administered to nude mice with implanted human prostate tumors. Prostate-specific antigen (PSA) is a known serum marker of prostate tumor cells specific activity. Recently, total serum homocysteine has been identified as a marker of tumor cell numbers with sensitivity for early detection of tumor cell death induced by treatments. A clinical trial with prostate cancer patients submitted to the association of ascorbic acid-menadione was performed and PSA/homocysteine was assessed in the follow- up. The early response in serum PSA and homocysteine levels was reported. The results showed that ascorbic acid-menadione produced an immediate drop in tumor cell numbers as assessed by homocysteine levels. Serum PSA levels showed an early rise and later dropped. These results suggest that autoschizis can also be induced by this pharmacological association at the clinical level in prostate cancer patients. Further studies are being performed in order to research if these results can be found with other primary tumors as it was shown in in vitro and experimental models. Ascorbic acid-menadione could be emerging as a new antitumoral chemotherapy.

Lately, the promising results obtained with autologous cancer vaccines are stimulating new research in the old field of cancer immunotherapy. This paper describes the development of a procedure previously reported by us that is used to obtain an autologous hemoderivative with antitumoral properties. The procedure has been tested in a phase I-II, randomized, controlled clinical trial of 28 cancer patients with different primary malignancies in metastatic and chemotherapy-resistant stages. The histology of the lesions that responded to this treatment was consistent with the characteristic histology observed in malignant lesions treated with a similar antitumoral hemoderivative: proliferation of stromal connective tissue, T-lymphocyte infiltration, and a reduction in the amount of tumor cells and blood vessels. We concluded that vaccination had elicited an immune response because a delayed-type hypersensitivity test made with the autologous hemoderivative produced a significantly more intense response in the responding treated patients. We propose that an immune mechanism acting on tumor cells and/or the regulatory system for stromal growth explains the histological results observed. The use of blood to obtain the immunogen allows vaccination to be repeated, so this method could avoid tumor escape responses due to mutations in the antigen library of the tumor. The results of our study justify further research to optimize the antitumoral effect of vaccination.

Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.

The autologous hemoderivative tested is antigenically polyvalent and promotes a polytargeted immune response associated with a tumor antiprogressive effect, consequently, acting as an autologous hemoderivative cancer vaccine.