Boosting Mesothelioma Survival with VEGF-Inhibitor

The VEGF inhibitor cediranib may not yet be out of the running as a mesothelioma treatment.

Although previous studies have found it to have dose-limiting side effects, a new study in the Journal of Thoracic Oncology finds that, at the right dose, it could boost the effectiveness of standard mesothelioma chemotherapy.

What is Cediranib?

Cediranib, an oral drug made by Astra Zeneca, is a powerful inhibitor of vascular endothelial growth factor (VEGF), a signal protein that can stimulate the growth of cancer cells.

Research has found that mesothelioma patients who have higher serum levels of VEGF have a lower chance of survival. Cediranib has the ability to counter the effects of VEGF by latching onto VEGF receptor sites inside cancer cells, preventing the protein from having an effect on those cells.

Cediranib in Mesothelioma Treatment

In 2011, an NIH study found that cediranib could significantly shrink tumors in people with alveolar soft part sarcoma, a rare malignancy for which no other chemotherapy drugs had been effective. But a 2012 study of cediranib in mesothelioma patients found that most could not tolerate the drug at doses higher than 45 milligrams and many still had serious side effects like hypertension and blood clots at 30 milligrams.

For the new Phase I trial, mesothelioma researchers cut the dose in half and combined it with standard chemotherapy. In this study, most pleural mesothelioma patients who received 20 milligrams of cediranib along with pemetrexed and cisplatin did not experience side effects that were serious enough to stop the study.

The mesothelioma patients selected for the study had been deemed inoperable and had not yet received any chemotherapy. They were treated with 6 cycles of chemotherapy along with cediranib.

Although some did experience a drop in white blood cells, gastrointestinal upset, and low blood platelets, at six weeks, the disease control rate was 90 percent. The median overall survival for patients on this regimen was 16.2 months.

“Cediranib combined with cisplatin-pemetrexed has a reasonable toxicity profile and preliminary promising efficacy,” writes oncologist Anne Tsao, MD, of MD Anderson Cancer Center in Texas.

Next Steps for Cediranib

The next step for the supplemental use of cediranib in the chemotherapeutic treatment of malignant mesothelioma is to test the combination in a planned Phase II trial. Phase I clinical trials establish dose and safety while Phase II trials focus on a drug’s effectiveness.

Although most mesothelioma patients receive chemotherapy as part of their treatment, it is only moderately effective. Even with the gold standard chemotherapy regimen of pemetrexed and cisplatin, mesothelioma is usually fatal within a year.

A number of new and ongoing mesothelioma studies are focused on potential methods for boosting the power of chemotherapy.

Sources:

Tsao, AS, et al, “Phase I Trial of Cediranib in combination with cisplatin and pemetrexed in chemo naive patients with unresectable malignant pleural mesothelioma (SWOG S0905)”, June 6, 2017, Journal of Thoracic Oncology, Epub ahead of print

Campbell, NP et al, “Cediranib in Patients with malignant mesothelioma: A phase II trial of the University of Chicago Phase II Consortium”, July 23, 2012, Lung Cancer, Epub ahead of print