A widely used drug that deters anemia in chemotherapy patients may actually do more harm than good, according to a study headed by Punam Malik, a physician-scientist at the Saban Research Institute of Childrens Hospital Los Angeles.
Malik, who is an assistant professor of pediatrics and pathology at the Keck School of Medicine, led the study by CHLA researchers, which found that the drug erythropoietin (EPO) may help cancerous tumors survive. The findings appear in the October issue of Laboratory Investigation.
“We discovered in our laboratory that erythropoietin, which is routinely given to cancer patients with anemia to help create red blood cells, also helps cancer cells to not only survive, but to grow and acquire a blood supply to help them thrive,” Malik said.
Malik’s research team focused its scientific inquiry on pediatric solid tumors of 25 pediatric cancer patients being treated at CHLA, and in 25 different cell lines derived from children’s solid tumors (not those of adults). “We feel that EPO should be used with extreme caution when used to improve anemia for childhood cancers,” she said.
The cause for concern in this finding is that EPO is the standard of care for adults with cancer who are anemic, since it was considered a growth factor restricted to red blood cells.
Malik said hundreds of clinical trials over the years have examined the effectiveness of EPO to make more red blood cells, but none of them looked at the outcomes. They focused only on whether or not EPO did, in fact, create more red blood cells.
The findings in Malik’s study are supported by a recent study of 351 cancer patients in Europe, published in the journal, Lancet. It found that EPO, which is believed to help radiation work better in cancer patients, did not prolong life, and might have even impaired cancer treatment in some patients.
Malik’s study is believed to be the first to have examined this use of EPO in pediatric patients, because EPO is not routinely given to children with cancer because, “We would have to administer several injections of EPO and we try to avoid sticking kids with needles,” she said. “We prefer to give them a blood transfusion to increase their red blood cells.”
Malik said that kids are much more resilient than adults. “If an adult’s hemoglobin count drops to eight, they are very tired and lethargic,” she said. “If a child has the same hemoglobin count, they tolerate the anemia better and are running around, dragging their IV poles with them.”
When the human body is low on oxygen (hypoxia) it gives a signal and the body makes more erythropoietin, which in turn makes more red blood cells. Initially, a tumor has no blood supply, and must create its blood vessels to survive. Malik wondered if tumors create EPO to attract a blood supply.
“We discovered that all of the pediatric tumors we examined produced EPO and responded to EPO by attracting blood vessels and increasing the activity of ‘survival’ genes,” she said. “Therefore, by giving a cancer patient EPO to cure his anemia, you also are helping his cancer cells to thrive by providing them with the source of blood vessels and arming them with pro-survival molecules.”
The lead author on the study was Sandeep Batra, a fellow in the division of hematology/oncology at Childrens Hospital. The 18-month study was funded by the Children’s Cancer Research Fund, which awarded Malik $25,000 for the first year and an additional $40,000 for the second year of the study.