Studies Highlight Limited Success of Mesothelioma Anti-Angiogenesis Drugs

Two recent mesothelioma studies suggest that anti-angiogenesis drugs may not be as successful as previously hoped in treating mesothelioma.

An anti-angiogenesis drug is a substance that inhibits the growth of new blood vessels (angiogenesis). The theory was first developed by Dr. Judah Folkman who pioneered research on tumor angiogenesis, the process by which a tumor attracts blood vessels to nourish itself and sustain growth. According to his theory, by introducing drugs that stop the formation of new blood vessels (anti-angiogenesis) tumors would not get the nourishment they need and would be unable to continue growing. This theory has attracted a lot of attention and investment in mesothelioma research.

One angiogenesis promoter that is found expressed in mesothelioma cells is called vascular epithelial growth factor (VEGF). A recently published article reported on a phase II study of the oral VEGF receptor tyrosine kinase inhibitor called cediranib. Cediranib was administered to 54 malignant pleural mesothelioma patients after they received platinum-based systemic chemotherapy.

According to the study, of the 47 evaluable patients, 4 patients (9%) had objective responses (tumors getting smaller), 16 patients (34%) had stable disease (no increase or decrease in tumors), 20 patients (43%) had disease progression, 2 patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death. The median overall survival was 9.5 months. The researchers concluded that “cediranib monotherapy has modest single-agent activity in malignant pleural mesothelioma after platinum-based therapy.”

And a Canadian study recently tested sunitinib, another VEGF inhibitor in 35 malignant mesothelioma patients. Only one patient had an objective response where the tumor decreased in size. The median survival was 8.3 months in the group of patients that had previously received cisplatin-based chemotherapy. Median survival was 6.7 months in the patients that were previously untreated. The researchers concluded that “sunitinib, similar to other angiogenesis inhibitors, has limited activity in malignant pleural mesothelioma.”

According to the National Cancer Institute, there are at least four anti-angiogenesis clinical trials currently recruiting mesothelioma patients for additional mesothelioma research. These include: 1) Avastin Plus Pemetrexed-cisplatin Study, 2) Axitinib in Malignant Mesothelioma, 3) Pilot Study of Bisphosphonate Therapy (Zoledronic Acid) in Patients With Malignant Mesothelioma (UAB 0901), 4) Sunitinib and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Chemotherapy.

Sources:

Garland LL, et al., Phase II Study of Cediranib in Patients with Malignant Pleural Mesothelioma: SWOG S0509, J Thorac Oncol. 2011 Nov;6(11):1938-45. Laurie SA, et al., Brief Report: A Phase II Study of Sunitinib in Malignant Pleural Mesothelioma. The NCIC Clinical Trials Group, J Thorac Oncol. 2011 Nov;6(11):1950-4.