CHICAGO—Twice-daily dosing of naproxen can reduce the incidence and severity of bone pain in cancer patients being treated with pegfilgrastim, according to data presented at the 2010 annual meeting of the American Society of Clinical Oncology.
As such, “naproxen…should be considered for patients beginning pegfilgrastim, providing there are no contraindications,” concluded Jeffrey J. Kirshner, MD, director of research and Community Clinical Oncology Program principle investigator from Hematology-Oncology Associates of Central New York, East Syracuse. “However, a significant percentage of patients still will experience pegfilgrastim-induced pain, and there is a need to develop even more effective preventive treatments.”
By stimulating bone marrow production of neutrophils, pegfilgrastim, an immunostimulator, functions as a pegylated granulocyte colony-stimulating factor. It is indicated for reducing the risk of infection in patients with certain types of tumors who require strong chemotherapy.
Pegfilgrastim-induced bone pain, however, is a significant clinical problem, which may result in discontinuation of treatment and lead to less effective chemotherapy dosing.
For this randomized, double-blind, placebo-controlled trial, 510 patients from 17 sites were randomized to receive either naproxen (500 mg twice daily) or placebo on the day of pegfilgrastim administration, and for 5 to 8 days thereafter. Eighty-six percent of the patients enrolled were women, 67% of enrollees had breast cancer.
Eligible patients included those with a diagnosis of non-myeloid malignancy who were scheduled to receive chemotherapy and a first dose of pegfilgrastim on day 2, 3, or 4 of the chemotherapy cycle. Patients could have no history of active or past gastrointestinal bleeding, have no allergies to nonseroidal anti-inflammatory drugs (NSAIDs) or be currently taking NSAIDs or any medication for preexisting chronic pain, or have undergone heart surgery within the previous 6 months.
Patients were asked to record pain duration and severity and were assessed using the University of Rochester Cancer Center Symptom Inventory Assessment. The primary outcome measure was the area under curve (AUC) for pain during days 1 through 5.
In both the placebo and naproxen groups, pain peaked at approximately 3 days after pegfilgrastim administration. Mean AUC for pain was significantly reduced from 7.71 in the placebo group to 6.04 in the naproxen group (P = .037).
Naproxen was associated with significant reductions in maximum pain (from 3.40 in the placebo group to 2.59 in the naproxen group; P = .005), the overall incidence of pain (from 76.3% to 65.6%, respectively; P = .01), and the duration of pegfilgrastim-induced bone pain (from 2.40 to 1.92 days, respectively; P = .005). A reduction in severe pain, defined as >5 on a 1 to 10 scale, was of borderline significance, with a reduction from 24.5% in the placebo group to 17.6% in the naproxen group (P = .0643).
No significant adverse events occurred in either group. Associations between the incidence, severity, or preventability of pegfilgrastim-induced bone pain and specific risk factors could not be found.
“There was a suggestion that pegfilgrastim-induced pain may be more frequent in African Americans, with an AUC of 12.88 as opposed to 6.48 in the non-African Americans. But there were only 33 African Americans [in this study], so I’m not sure what to make of this,” noted Kirshner.