Abstract
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.
Highlights
Classical chemotherapy, which exerts its antitumor activity by causing damage and inducing apoptosis in rapidly dividing cells, has been a corner stone in standard cancer treatment for several decades
The addition of the tested regimen in group 2 (G2), which is a recognized procedure for eliciting antiangiogenesis and antitumor immunity, improved the survival rate compared with group 1 (G1) patients who were only treated with chemotherapy
The mean survival was significantly longer for G2 patients than for G1 patients for the three tumor types analyzed: 18.0 versus 10.2 months, 16.7 versus 12.1 months, and 20.4 versus 16.8 months for pancreatic cancer, non-small-cell lung cancer (NSCLC), and prostate cancer, respectively
Summary
Classical chemotherapy, which exerts its antitumor activity by causing damage and inducing apoptosis in rapidly dividing cells, has been a corner stone in standard cancer treatment for several decades. The rationale for using classical chemotherapy is to kill malignant cells in order to reduce tumor size. This method has not provided satisfactory benefits for patients with advanced cancers and poor prognoses in terms of survival. Med Oncol (2012) 29:3626–3633 experience disease progression after a short period of remission, if any, despite treatment with classical chemotherapy. This progression requires residual cancer cells, and a biological response permissive to and conditioned by the malignancy, according to several reports in the current literature [1, 2]. In addition to using treatments that kill cancer cells, targeting these additional components may improve the antiprogressive efficacy of the treatments
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