Etanercept and chemo might reduce fatigue in cancer patients

May 3 2006

Researchers here have found evidence that combining a drug typically used to treat rheumatoid arthritis with chemotherapy might help reduce fatigue and muscle wasting that often afflicts cancer patients.

The findings of the preliminary study with 24 patients are reported in the Journal of Clinical Oncology.

"Even though this was a small study, we found that we could deliver more chemotherapy when combined with the drug etanercept," said lead author Miguel A. Villalona-Calero, an associate professor of hematology and oncology and of pharmacology at Ohio State.

"This shows promise in helping reduce fatigue in cancer patients while increasing their ability to tolerate higher doses of chemotherapy on a more frequent basis," said Villalona-Calero, who is also researcher at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).

Patients' fatigue - the state of overwhelming and sustained exhaustion that is not relieved by rest - often hinders physicians' ability to deliver chemotherapy to them on schedule because of their weakened state.

The fatigue and muscle wasting that are associated with cancer are largely caused when immune cells release a substance known as tumor necrosis factor (TNF). Although TNF historically has been studied for its anticancer properties, recent studies indicate that TNF probably promotes tumor growth instead of hindering it.

The drug etanercept is a decoy receptor that blocks interaction with TNF. The researchers hypothesized that the drug might therefore work like a sponge to "soak up" TNF and lower the amount of the substance in the body, which would decrease tumor growth and help reduce fatigue.

They tested the idea in patients who were being treated with the chemotherapy drug docetaxel.

Initially, 12 patients with a variety of advanced solid malignancies that were resistant to conventional treatment, or for which no effective treatment existed, were randomly assigned to two groups, one receiving docetaxel, and one receiving docetaxel along with etanercept. Subsequently, an additional 12 patients who were later added to the study received higher doses of docetaxel combined with etanercept.

Patients were evaluated and answered weekly questionnaires about their perceived fatigue and weakness. Although only a limited group of patients received docetaxel without etanercept, the questionnaires showed that they have increased fatigue compared to the patients who received etanercept.

Researchers concluded that the addition of etanercept is safe and had no impact on the concentration of the chemotherapy drugs in the body. The finding that patients could tolerate higher doses of the chemotherapy drug suggests that the use of drugs to block TNF might improve the effectiveness of cancer therapies, Villalona-Calero said.

Others involved in the study were J. Paul Monk, Michael A. Caligiuri, Larry J. Schaaf, Gregory W. Otterson, Denis Guttridge, Chris Rhoades, Manisha Shah, Gary Phillips and Tamara Criswell, all of the Ohio State cancer program.