When a patient or caregiver speaks of immunotherapy it is often with a more confident tone than when they are speaking about chemotherapy. However, the odds of a patient going into remission are still greater with chemotherapy.
Dr. Christian H. Ottensmeier, co-leader of the UK study, told Oncology News that only twenty to thirty percent of patients receiving immunotherapy will experience remission.
That includes patients who have spreading and metastatic disease. Dr. Ottensmeier commented that he has witnessed immunology curing some patients with cancer in advanced stages.
However, the majority of patients receiving immunotherapy may experience no change, or develop severe problems with the lungs, bowel, or skin while in treatment. These side effects are not only debilitating, causing cessation of treatment, but may also be fatal.
A Failed Clinical Trial
Researchers in the United Kingdom (UK) at Liverpool University, together with a team from the LaJolla Institute in California, conducted a study using samples from a UK clinical trial. The patients had cancers of the neck and head.
Gradually the UK patients began to experience severe side effects. Twelve patients out of the twenty-one who participated in the trial developed colitis, which is inflammation in the colon. The researchers had expected this oral cancer immunotherapy, P13Kd, to be non-toxic.
Teams from both institutes immediately revisited data and patient samples to determine the effect of the P13Kd inhibitor on immune cells.
Their efforts brought results. The findings provided clues to the reason certain immunotherapies cause debilitating side effects. They also opened a pathway to improved methods of treating patients who have solid tumors.
The Cause: P13Kd Inhibitor
Patients in the failed clinical trial had been administered P13Kd, a new immunotherapy that had not been tested for solid tumors. Although P13Kd has been proven to be effective, its side effects can be severe. It is therefore used mostly where all other options have failed or are deemed to be unsuitable.
Immunotherapy involves substances that either stimulate or suppress the immune system. P13Kd inhibitors are a class of drugs that block the PI3K/AKT/mTOR pathway and slow down the growth of cancer.
However, P13Kd can also be active in cancer cells where it allows the cancer cells to survive and multiply.
The team was actively engaged in the process of improving the role of T cells to fight tumors. During the process, however, the researchers discovered that the P13Kd inhibitor blocked a Treg cell group that protects the colon. Without Treg’s protection, disease-causing T cells took over. The result was inflammation and colitis.
After a thorough investigation, there was little doubt that the clinical trial patients had been administered a higher dose of the P13Kd inhibitor than they were able to tolerate. It was also evident that immunotherapy disturbed the immune cells in the gut causing an imbalance.
The researchers decided to attempt a new strategy. The treatment would evolve into intermittent dosing. This could continue the anti-tumor immunity but with less toxicity. A new clinical trial is being designed to test intermittent dosing in humans.
