A combination of crizotinib and afatinib does a better job of inhibiting the growth of malignant pleural mesothelioma (MPM) cancer cells than either therapy alone, according to a study.
Together, the drugs, which are already approved to treat other cancers, cut mesothelioma tumor cell growth in mice in half. They also inhibited the growth of cancer cells in a laboratory.
The study, “Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma,” was published in the American Journal of Cancer Research.
MPM is a rare aggressive cancer caused by exposure to asbestos. Most patients are diagnosed in advanced stages so they do not benefit from chemotherapy or surgery. That means there is a pressing need for effective MPM therapies.
Two proteins are found at high levels in MPM tissue samples. One is cellular-mesenchymal to epithelial transition factor (MET), and the other epidermal growth factor receptor (EGFR).
Researchers studied tissue from 24 patients who died of MPM and 24 healthy controls for the presence of MET and EGFR. The MPM patients had MET, EGFR, or both, while the proteins almost never showed up in the controls.
MPM patients with either MET or EGFR in their tissue survived much longer than those who had both — 20.5 months versus 13.5 months, researchers found.
Similarly, when the research team eliminated either MET or EGFR from cancer cells grown in a lab, they saw little inhibition in cell growth. But when they eliminated both MET and EGFR, there was significant inhibition of growth.
The team then used drugs that target MET and EGFR to treat mice with MPM. Crizonitib targets MET and afanitib targets EGFR.
When either drug was used alone, there was little anticancer effect. But when the two were administered together, they reduced tumor growth by roughly half.
“Our results indicated that treatment with a combination of crizotinib and afatinib showed stronger inhibition on cell proliferation in MPM cells than treatment by either drug alone at both in vitro and in vivo levels. This represents a promising therapeutic strategy for MPM,” Liyan Huang, of the Collaborative Innovation Center for Cancer Medicine in China, and his colleagues concluded.