A Phase I study for cediranib, a VEGFR/PDGFR kinase inhibitor, showed promising results in shrinking tumor size and increasing survival rates for those suffering from malignant pleural mesothelioma. This is not the first time cediranib has been studied as a possible treatment for mesothelioma. In 2011/2012 a Phase II trial for cediranib conducted by researchers at the University of Chicago concluded that while there was some disease control when patients were given a 45mg dose, cediranib caused side effects that were too serious to move trials forward. Some of those side effects included fatigue, hypertension, angioedema, pulmonary embolism, confusion, headaches and vision loss. The dosage was then scaled back to 30mg, but scientists and researchers did not see any positive results, and the study was marked as a failure.
Now, the latest study of cediranib is focusing on these side effects when administered with cisplatin and pemetrexed; two common chemotherapy treatments for mesothelioma. It is believed that cediranib may stop cell growth by blocking blood flow to the tumor and also by blocking enzymes that are responsible for cell/tumor growth. The Phase I study was divided into 2 cohorts – the first cohort contained 7 patients receiving 30mg of cediranib and the second cohort was 13 patients receiving 20mg of cediranib, over 6 cycles.
Serious side effects are still apparent with the most common being diarrhea, dehydration, fatigue and neutropenia. Thrombocytopenia (low blood platelet count) was also reported, along with one treatment-related death. Those receiving 20mg of cediranib continued to do so daily as less instances of toxicity were reported. In the end, overall survival was 16 months. The randomized Phase II portion of the trial is currently ongoing; focusing on a 20mg/day dosage.
A mesothelioma diagnosis is devastating to the victims and their family. This fatal cancer has no cure, and survival time after initial diagnosis is typically less than one year. Decreasing tumor size can help increase survival time and scientists and researchers are continually investigating new techniques and treatments for tumor shrinkage. Even though many treatments fail, or don’t have the desired results, it’s important for mesothelioma patients to not give up hope. As we have seen here with cediranib, initial testing from half a decade ago did not improve the condition of patients. Researchers and scientists built off of the positive results in the initial trial and used those components when investigating the new technique of adding cediranib with cisplatin and pemetrexed.
This study is ongoing, but not recruiting participants. Read more at ClinicalTrials.gov.
Source:
Anne S. Tsao, et. al “A phase I study of cediranib (NSC #732208) in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma (SWOG S0905).” Journal of Clinical Oncology (June 2017). [Link]
