Rheumatoid arthritis drug may decrease chemotherapy fatigue and help it work better

[Lani]

Arthritis Drug Might Reduce Fatigue in Cancer Patients [Ohio State University]
COLUMBUS, Ohio - 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 April 20 issue of 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.

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REPRINT: ABSTRACT: Assessment of Tumor Necrosis Factor Alpha Blockade As an Intervention to Improve Tolerability of Dose-Intensive Chemotherapy in Cancer Patients [Journal of Clinical Oncology; Subscribe; Sample]
Purpose: Maintaining dose-intensity with chemotherapeutic agents is hindered by a number of adverse effects including asthenia/fatigue. Tumor necrosis factor (TNF) is one of the cytokines responsible for the fatigue and cachexia associated with malignancies. We used etanercept (TNF-decoy receptor) to maintain dose-intensity of weekly docetaxel.

Patients and methods: Initially, 12 patients with advanced malignancies were randomly assigned to either docetaxel 43 mg/m2 weekly alone (cohort A) or the same docetaxel dose plus etanercept 25 mg subcutaneously twice weekly (cohort B). Subsequently, higher doses of docetaxel in combination with etanercept were evaluated. Pharmacokinetics (PKs), nuclear factor-kappa B (NF-?B) activation, and intracellular cytokines levels were measured. Patients completed weekly questionnaires quantifying asthenia/fatigue.

Results: Twenty-nine of 36 intended docetaxel doses during the first cycle were delivered in cohort A, and 35 of 36 doses were delivered in cohort B (P = .055). Three cohort B patients received additional cycles in the absence of disease progression or severe toxicity, whereas no patients from cohort A received additional cycles. Escalation to docetaxel 52 mg/m2 weekly with etanercept resulted in neutropenia, not fatigue, as the limiting adverse effect, and the addition of filgrastim permitted the maintenance of dose-intensity in additional patients. Patients randomly selected to receive etanercept/docetaxel self-reported less fatigue (P < .001), and docetaxel PKs show no relevant influence of etanercept. NF-?B activation and increased expression of TNF-? were associated with increments in docetaxel dose. Antitumor activity was noticed exclusively in patients receiving etanercept.

Conclusion: The addition of etanercept is safe and had no impact on docetaxel concentrations. The significant improvement in tolerability and the trend toward preservation of dose-intensity suggests further exploration of TNF blockade as an adjunct to cancer therapies.