Adding a hypoxia-activated prodrug (HAP) to standard care for epidermal growth factor receptor-positive non-small cell lung cancer may help to delay treatment resistance, according to a study published in PLOS Computational Biology.
Cancer tumors with low levels of oxygen (hypoxia) have been known to be more resistant to treatment and generally grow much more quickly than those with normal oxygen levels. The condition can be treated with HAPs; however, these drugs on their own are not effective as a single treatment.
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To try and find a way of increasing the success of HAP use, researchers led by Jasmine Foo, University of Minnesota, Minneapolis, developed a mathematical model to assess the effectiveness of using evofosfamide, an investigational HAP, in combination with standard cancer therapy in patients with epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer.
The researchers tested a number of different drug combinations, but ultimately found that the best results were achieved with alternating treatment of evofosfamide and erlotinib while limiting the time between doses.
Compared with standard care, this method significantly delayed treatment resistance and reduced patients’ time to progression by 40.54%. In addition, alternating single doses of each drug led to minimal tumor burden, although increasing dosage worsened toxicity and the probability of patients developing resistance.
“…alternating frequently between the two drugs allows the entire population of cancer cells in the tumor microenvironment to be constantly controlled by the drugs,” authors of the study concluded. “These results demonstrate that incorporating HAPs in combination with targeted therapies may be an effective tool in preventing resistance, and suggest an alternative use for HAPs.”
They added that the results demonstrated in their model would first need to be tested in a clinical context before they can be implemented into everyday practice. Still, their data provide a novel framework for defining drug toxicity constraints and show how HAPs can be used effectively when combined with other therapies.
