Women given pegfilgrastim to prevent myelosuppression after chemotherapy for breast cancer often develop bone pain — but a small clinical trial suggests that delaying the drug by just one extra day can lessen the side effect.

Researchers found that beginning pegfilgrastim (Neulasta) on day 3 after the final chemotherapy dose reduced the incidence of severe bone pain vs giving it on day 1 or 2 — from as many as two thirds of patients to just under one quarter.

And the delay did not appear to raise the risk for neutropenia, according to findings published in the Annals of Internal Medicine.

“We should constantly be looking to improve not only the efficacy of our treatments but also the tolerability,” said Douglas K. Marks, MD, breast oncologist at NYU Langone Health in New York City who was not involved in the study.

He told Medscape Medical News that if simply adjusting the timing of pegfilgrastim can reduce bone pain, it would be a “meaningful improvement in patient experience.”

Marks cautioned, however, that larger studies are needed before there can be a strong recommendation for all patients to start pegfilgrastim on day 3 — which is near the end of the standard dosing window.

Current guidelines from the National Comprehensive Cancer Network say that pegfilgrastim should be administered within 1-4 days after chemotherapy to help prevent myelosuppression.

Some prior research has suggested that patients tend to have less bone pain if they receive the drug later within that time window. But no studies have specifically tested whether treatment timing changes patients’ risk of the side effect.

To do so, researchers at Southern Medical University in Guangzhou, China, recruited 159 women with stage I-III breast cancer who were scheduled to begin their first round of chemotherapy with either nab-paclitaxel plus cyclophosphamide or nab-paclitaxel plus carboplatin.

The patients were randomly assigned to start pegfilgrastim 24, 48, or 72 hours after their last chemotherapy dose.

The study’s primary endpoint was area under the curve (AUC, ranging from 0 to 40) of the daily worst bone pain score over 5 consecutive days, starting from the day of pegfilgrastim administration. Patients reported the score using the “worst pain” question from the Brief Pain Inventory-Short Form (0 = no pain, 10 = worst pain).

Overall, the study found, the mean AUC for the 72-hour group (6.05) was significantly lower than for the 24-hour and 48-hour groups (12.74 and 14.20, respectively; P < .001).

Patients in the 72-hour group also had a significantly lower incidence of severe bone pain (22.6%) than the 24-hour (58.5%) and 48-hour (66%) groups (P < .001).

There were no statistically significant differences between the groups in the incidence of neutropenia, and no patients developed febrile neutropenia.

“Administration of pegfilgrastim 72 hours after chemotherapy could serve as a viable strategy in clinical practice to improve the overall treatment experience for patients,” the authors wrote.

It’s unclear why the delay might lessen bone pain. The researchers noted that pegfilgrastim-induced bone pain is thought to be related to bone-marrow expansion, increased pain sensitization, and modulation of immune function. In addition, taxane chemotherapy can itself cause acute pain.

More research is needed to see whether the reduced bone pain in the 72-hour group is linked to any of those factors, the investigators wrote.

As for the findings on neutropenia, Marks said they are in line with several patient series reporting no increase in febrile neutropenia with delayed pegfilgrastim administration.

Still, the study authors agreed that larger confirmatory trials are necessary, and until then, their results should be interpreted cautiously.

Even if the findings are confirmed, Marks pointed to a potential logistical stumbling block: At many cancer centers, patients receive pegfilgrastim via an auto-injector system that’s applied on their final day of treatment to obviate the need for an additional office visit.

Many of those devices, Marks said, are timed to begin pegfilgrastim delivery about 24 hours after application and cannot be adjusted.

“If and until these device parameters can be adjusted,” he said, “patients would have to weigh the convenience of these systems [against] the potential reduction in bone pain associated with later administration.”

The trial was funded by the National Natural Science Foundation of China and the Deng Feng project of high-level hospital construction. The authors reported having no disclosures. Marks reported disclosing financial relationships with AstraZeneca, Lilly, Merck, and others.