A biotech drug widely used to combat chemotherapy-induced anemia in cancer patients may actually be counterproductive, helping cancer cells survive, say researchers from Childrens Hospital Los Angeles.
A study found that the drug, erythropoietin, or EPO, promoted growth of blood vessels, which in turn nourished tumors in cells from 25 different forms of pediatric cancer.
EPO is not usually used to treat pediatric patients, but the team feared the same effects may occur in tumors from adults. Their findings, reported in the current issue of the journal Laboratory Investigation, support earlier hints that EPO treatment may be problematic.
European scientists reported last month that EPO treatment of 351 cancer patients did not prolong life and might even have impaired treatment in some of those receiving it.
Because of those studies, "We now have concerns that EPO should not be used in cancer patients unless we do very strict studies" about its safety, said Dr. Punam Malik, who led the most recent study.
"The major limitation of the study, and this is very important, is that it was just a study of cells in the test tube, in the laboratory," said Dr. Stuart Siegel of Childrens Hospital, who was not involved in the study but is familiar with the results. "We are a long way off from saying that this is important for a patient ... but it definitely needs to be followed up, first in animals and then, if an effect is observed, in patients."
Malik and her colleagues are already planning a trial to try to detect adverse effects from the drugs in pediatric patients.
EPO -- marketed as Epogen by Amgen Inc. of Thousand Oaks and as Procrit by Ortho Biotech of Bridgewater, N.J. -- is the genetically engineered form of a natural hormone that combats anemia by stimulating production of red blood cells. It costs from $500 to $1,000 per dose and is one of the best-selling drugs in the United States.
EPO is the standard of care for treating anemia in adult cancer patients, but it is used infrequently in children with tumors.
"We would have to administer several injections of EPO, and we try to avoid sticking kids with needles," Malik said. "We prefer to give them a blood transfusion to increase their red blood cells."
Malik and her colleagues decided to study whether EPO acts on cells outside the circulatory system. They examined cells from 25 different types of freshly excised pediatric tumors, such as neuroblastomas, Ewing's sarcomas and brain tumors.
"We discovered that all of the pediatric tumors we examined ... responded to EPO by attracting blood vessels" and increasing the activity of genes that bolster the tumor cells' ability to survive, she said.
"Therefore, by giving a cancer patient EPO to cure his anemia, you are also helping his cancer cells to thrive by providing them with the source of blood vessels and arming them with pro-survival molecules," she said.
Malik's group obtained the same results using cultured cell lines derived from adult tumors, but she cautioned that such cells often change some characteristics once they become adapted to growing in culture.
"That's not as trustworthy as seeing the genes being expressed in fresh tumor cells," she said.
Few researchers were sufficiently aware of the study to comment on it.
Doug Arbesfeld, a spokesman for Ortho Biotech, said: "The study is based on in vitro [test tube] data. To better understand this laboratory finding, clinical research will be required."
The European study, conducted by Dr. Michael Henke and his colleagues at the University of Freiburg in Germany, was designed to determine whether EPO improved the outcome in patients receiving radiation therapy for cancers. Earlier studies had suggested that radiation was less effective in anemic patients.
Half of the 351 patients in the trial received EPO manufactured by Hoffmann-LaRoche, and half received a placebo. Overall, 61% of those receiving the drug died, compared with 52% of those receiving the placebo.
Henke said that he did not think the drug should be used in cancer patients except in clinical trials to determine its value.
Amgen officials criticized the European study, arguing that it was poorly designed. They said many patients did not receive the correct dosage of radiation, and many who received EPO were not seriously anemic.