Higher Doses of Tremelimumab Better at Halting Mesothelioma

The targeted mesothelioma therapeutic agent tremelimumab appears to work, but to achieve best results it turns out you have to take more of it for a longer stretch than researchers envisioned.

Fortunately, you’ll probably be able to tolerate the extra amount, according to research from Italy that appeared in the April 2015 issue of the British medical journal Lancet.

Tremelimumab is designed to help your immune system’s T lymphocyte cells attack and annihilate mesothelioma cells.

Normally, your immune system would have the ability to kill mesothelioma cells, but it can’t because mesothelioma cells spit out a protein called CTLA-4 — cytotoxic T lymphocyte-associated protein 4.

CTLA-4 is bad news because it normally interferes with the ability of your immune system’s T lymphocytes to kill cancer cells.

Tremelimumab, it so happens, can prevent CTLA-4 from interfering with the work of your T lymphocytes. Tremelimumab accomplishes this by binding to the CTLA-4 and creating what is known as an immune checkpoint blockade.

Up until now, mesothelioma patients taking tremelimumab usually receive 15 mg of the drug for each kilogram of their body weight. This is repeated once every 90 days.

However, researchers from University Hospital of Siena in Italy found evidence that this was too little, and that more would be better.

So they decided to conduct a Phase 2 study with a group of 29 mesothelioma patients who received tremelimumab at a higher dosage.

Mesothelioma Patients in Late Stages Chosen

The participants ranged in age from 42 to 78. All had mesothelioma in either stage III or IV – so far advanced that it was beyond treatment with surgery.

The disease was so far advanced, in fact, that none of the participating patients was expected to survive mesothelioma beyond another three months.

Also, to take part in this study, participants had to have received platinum-based chemotherapy at some point prior to enrollment — and this chemotherapy had to have failed.

Once enrolled, the mesothelioma patients were given 10 mg/kg of tremelimumab once every 30 days for six months, then once every 3 months until either their mesothelioma started progressing again or bad side effects surfaced.

Mesothelioma Halted in Many of the Patients

As a result, mesothelioma in more than half the patients stopped progressing. This halt lasted for a median of nearly 11 months.

Side effects did materialize in some of the patients. However, the side effects seen most often were fever, changes to the skin, and stomachaches.

“Our results suggest that the intensified schedule of tremelimumab investigated seems to have clinical and immunological activity in patients with advanced malignant mesothelioma, and a good safety profile,” the researchers wrote.

The researchers indicated they plan next to conduct a more comprehensive Phase 2 study to see if the results of the first Phase 2 study can be replicated and provide even richer insights.

This isn’t the first study looking into the efficacy of tremelimumab. Last year, a Phase 2 clinical trial of tremelimumab got underway at Georgia Regents University’s Cancer Center in Augusta, Georgia.

The Georgia Regents study of tremelimumab is still ongoing.