Nov
11
2023

New Treatment against Advanced Bladder Cancer

By | Cancer, laser therapy, Mortality

At a Cancer congress in Madrid, Spain a new treatment against advanced bladder cancer was discussed at this year’s European Society for Medical Oncology Congress. The standard treatment for advanced bladder cancer is gemcitabine in combination with cisplatin or carboplatin. According to CNN the median survival with the standard chemotherapy is 16.1 months. In contrast, treatment with the new intravenous antibody drug enfortumab vedotin in combination with intravenous pembrolizumab resulted in longer survival. The combination yielded a survival of 31.5 months for advanced bladder cancer patients. This new immunotherapy method resulted in a 96% longer survival. The safety profile of the two approaches were similar. 55.9% of patients taking the combination immune therapy developed skin rashes or hyperglycemia, while 69.5% of those taking platinum chemotherapy developed this.

Other new findings about advanced bladder cancer treatment

Dr. Thomas Powles is a professor of urology cancer at the University of London and director of the Barts Cancer Centre in the United Kingdom. He said:” The problem with chemotherapy is although it works quite well initially, resistance occurs quickly, and the median survival for metastatic bladder cancer has been about a year. What this study showed is, we did a big, randomized Phase 3 study where we compared a new treatment — two new drugs — with standard chemotherapy,” Powles said. “And in this randomized trial, when you gave those two drugs together, you reduced the risk of death for this cancer by over 50%. So, you’ve doubled survival, with patients living twice as long, and we’ve got long-term durable remission.”

Erdafitinib study

A second study from the New England Journal of Medicine used erdafitinib in comparison to standard chemotherapy. Erdafitinib is a small molecule inhibitor of fibroblast growth factor receptor and is effective in the treatment of cancer. This study compared 136 patients on erdafitinib with 130 patients on chemotherapy. Patients treated with standard chemotherapy had a median overall survival of 7.8 months. This compares to 12.1 median survival for the erdafitinib group. Erdafitinib, a kinase inhibitor drug, is slowing the spread of cancer cells.

Side effects that led to death were less common with erdafitinib than with chemotherapy. Only 0.7% of erdafitinib patients had serious side effects versus 5.4% of chemotherapy patients.

Nivolumab study

Another clinical trial was recently published in the New England Journal of Medicine.

Nivolumab is an immune checkpoint inhibitor that was originally developed for treatment of intractable melanoma. However, subsequently it was found to be active also against lung cancer, kidney cancer and bladder cancer. In the clinical study mentioned above 304 patients with intractable bladder cancer were treated with standard chemotherapy alone. They were compared to 304 patients on standard chemotherapy plus nivolumab.

The median complete response with the nivolumab-combination therapy was 37.1 months. In contrast, with gemcitabine–cisplatin alone it was only 13.2 months. Side effects of the two treatments were about similar. The authors concluded that treatment with the immune checkpoint inhibitor, nivolumab plus standard chemotherapy with gemcitabine–cisplatin resulted in better survivals than treatment with gemcitabine–cisplatin alone.

Discussion

Immunomodulation is one of the newest approaches to cancer treatment. But at the Hope 4 Cancer Clinic immunomodulation is only one aspect of a comprehensive approach to cancer treatment.They mention that they restore the microbiome in the gut. Great detail is spent to a full spectrum nutrition. Detoxification and non-toxic cancer therapies are employed. Oxygenation helps to restore the acid/base balance. Immunomodulation with the newer agents mentioned above helps as well to combat cancer. Low-dose laser photodynamic therapy with various light frequencies helps to destroy cancer cells as well. These lasers activate a variety of sensitizers, which are taken up by cancer cells and lead to their destruction. Finally, the cancer patients are taught how to achieve spiritual and emotional well-being. The Hope 4 Cancer Clinic demonstrates that treatment with immunomodulation is best combined with other treatment modalities to improve patient survival.

New Treatment against Advanced Bladder Cancer

New Treatment against Advanced Bladder Cancer

Conclusion

Physicians used three different immune therapies to treat advanced bladder cancer. Erdafitinib vedotin, a kinase inhibitor drug, in combination with intravenous pembrolizumab resulted in a survival of 31.5 months for advanced bladder cancer patients versus 16.1 months with standard chemotherapy. Another clinical trial showed that patients on standard chemotherapy had a median overall survival of only 7.8 months for advanced bladder cancer. This compares to 12.1 months median survival for the erdafitinib group. Finally, nivolumab, an immune checkpoint inhibitor was combined with standard chemotherapy. When end stage bladder cancer patients were treated with this combination, they survived 37.1 months. In comparison, the control group with chemotherapy alone (gemcitabine–cisplatin) survived only 13.2 months. There is definitely better survival of patients when immunomodulation is used. The hope is that future immunomodulators will have a stronger effect against cancer with less side effects.

Aug
13
2022

New Immunotherapy Approach against Cancer

By | Cancer, immune system

A recent publication reported about a new immunotherapy approach against cancer. The model it dealt with was a very vicious brain cancer with the name glioblastoma. The results of this research were subsequently transferred to another vicious cancer, osteosarcoma, which is a form of bone cancer with a very poor prognosis. Researchers have to do further clinical experiments to establish this new immunotherapy in osteosarcoma patients. Physicians completed the following experiments and clinical studies.

Oncolytic virus Delta-24-RGD can lead to remission in glioblastoma patients

Researchers at the University of Navarra, Pamplona, Spain together with The University of Texas MD Anderson Cancer Center in the US investigated glioblastoma patients. They found that treatment of glioblastoma patients with oncolytic viruses Delta-24-RGD led to a greater than 3-year remission in 20% of cases. Normally, patients with a glioblastoma survive only 9 months on average. 12% had a greater than 95% reduction in the size of the tumor. This was a phase 1 clinical study with 37 patients who had recurrent malignant glioblastoma. The authors said: “Oncolytic adenoviruses are attractive therapeutic agents because they can kill tumor stem cells and induce cell death by several mechanisms, including direct lysis, expression of toxic proteins, induction of cytokines, and T-cell–mediated immunity.” The particular oncogenic virus that the researchers used was an adenovirus Delta-24-RGD.

Transferring glioblastoma results to a cure for osteosarcoma

The same researchers wanted to see whether the cure rates of treating patients with glioblastoma was transferable to other cancer patients. In particular they were interested in patients with osteosarcoma, which is a similarly vicious cancer. Advanced osteosarcoma has a survival rate of 27% after 5 years. The researchers first did experiments with a human osteosarcoma cell line in tissue culture and at the same time a murine osteosarcoma cell line. Later they tested the action of oncolytic viruses Delta-24-RGD in a mouse model.

Experiments with osteosarcoma cells in tissue culture

The advantage of such experiments is that you can control all the parameters easily in a Petri dish. But critics say that this is far removed from osteosarcoma behavior in humans. Researchers found that the oncolytic virus Delta-24-RGD killed many osteosarcoma cells in vitro. They also were able to insert a new gene into the oncolytic virus, which was equally effective in killing osteosarcoma cells. They called this virus Delta-24-ACT.

Curing osteosarcoma in a mouse model

Next the researchers tested effectiveness of the oncolytic viruses, Delta-24-ACT and Delta-24-RDG in mice. They injected osteosarcoma cells from tissue culture into the tibia of mice. Tumor growth was subsequently measured. The experimental groups were given two oncolytic virus infections, the control group did not. On day 10 and 18 the researchers could see that controls had faster growing tumors compared to the experimental groups. The experimental groups had less tumor side effects. And the experimental mice survived longer than the controls. Further research showed that the oncolytic viruses produced a 4-1BBL protein, which stimulated the animals’ immune system to fight the osteosarcoma.

New immunotherapy approach against cancer: Effector T cells

Researchers could prove that in mice treated with oncolytic viruses it was the special protein (4-1BBL) that stimulated T lymphocytes to become killer T cells. They in turn attacked the osteosarcoma cells.

New immunotherapy approach against cancer: The need for human research

Doing research in humans is more complicated than in a mouse model. But in order to improve survival rates in patients with osteosarcoma human research is absolutely essential. However, research is complex and the effects of oncolytic viruses is only in the 20% range with regard to increasing survival. This requires more research. It may be that instead of oncolytic viruses a stimulatory protein would arm T cells to become killer T cells that fight the cancer.

New Immunotherapy Approach against Cancer

New Immunotherapy Approach against Cancer

Conclusion

Glioblastoma patients had a better survival after treatment with oncolytic viruses Delta-24-RGD. Researchers translated this type of research to another cancer, osteosarcoma. This also has a poor prognosis, Researchers did experiments in tissue culture and in a mouse model. They were able to show that oncolytic viruses produced a 4-1BBL protein, which stimulated the animals’ immune system to fight the osteosarcoma. Specifically, the protein armed T lymphocytes and turned them into killer T lymphocytes. These destroyed osteosarcoma cells in tissue culture or in the mouse model. It is encouraging to see positive results in a laboratory setting of a tissue culture. The step further in an animal experiment is also a positive achievement. More research will improve the cure rates of osteosarcoma. The effective treatment of osteosarcoma in humans is still far away! The next step is human research that shows improvements in patients’ survival rates.