Breast cancer patients who tolerated their first two paclitaxel infusions had few hypersensitivity reactions after stopping prophylactic medications – and reported less insomnia and unwanted appetite increases, according to new research.
Patients receiving paclitaxel may be able to ditch their infusion premedications after two uneventful doses, according to the first prospective randomised trial to test the strategy.
The study found that among patients with breast cancer who stopped all premedications after their first two paclitaxel doses, just one experienced an infusion hypersensitivity reaction (iHSR) that required treatment with rescue medication.
No such reactions occurred among patients who continued the standard prophylactic regimen.
Dropping the premedications was also associated with fewer troublesome side effects, including sleep disturbance and unwanted increases in appetite.
The findings, published in the Journal of the National Comprehensive Cancer Network, suggest that routinely continuing dexamethasone, antihistamine, and H2 antagonist prophylaxis throughout paclitaxel treatment may be unnecessary for patients who tolerate their first two infusions.
“At the time this trial was developed, a growing body of published data suggested that if a patient had not experienced an iHSR after 2 doses of paclitaxel, the likelihood of a reaction with subsequent doses was low,” the researchers wrote.
“This provided rationale for conducting a randomised clinical trial to evaluate the safety of discontinuing premedications in patients who tolerated paclitaxel.
“Positive findings from such a study could influence clinical practice by reducing chemotherapy administration time, lowering health care costs, and potentially decreasing dexamethasone- and diphenhydramine-related toxicities.”
Paclitaxel has long been associated with infusion hypersensitivity reactions, with rates as high as 41% reported in early studies conducted before routine prophylaxis, the researchers said.
Patients were therefore typically premedicated with a corticosteroid such as dexamethasone, an H1 antagonist such as diphenhydramine, and an H2 antagonist such as famotidine.
But that protection came with its own issues. Repeated dexamethasone exposure could cause hyperglycaemia, insomnia, gastritis, fluid retention, weight gain, mood changes, and immunosuppression, while parenteral diphenhydramine could cause drowsiness, dizziness, dry mouth, constipation, agitation, and falls, the researchers noted.
Previous studies have suggested that patients who get through their first two paclitaxel doses without an iHSR had a low risk of subsequently developing one, prompting the US researchers to test whether all prophylaxis could safely be stopped.
The open-label, single-institution trial enrolled adults with breast cancer scheduled to receive at least four doses of paclitaxel, either 80mg/m² weekly or 175mg/m² every 14 days.
All participants received standard prophylaxis for their first two paclitaxel doses. Those who had no hypersensitivity reaction were then randomised either to continue the premedications or stop them altogether from their third dose onwards.
The primary endpoint was an iHSR requiring parenteral rescue medication, which could include corticosteroids, diphenhydramine, famotidine, or epinephrine. Researchers also tracked weight, treatment-related symptoms, and quality of life.
Of 130 patients initially enrolled, 29 experienced an iHSR during one of their first two paclitaxel infusions and therefore did not proceed to randomisation.
Ninety-eight patients were randomised, with 89 ultimately evaluable. Of these, 46 in the control arm continued their premedications and 43 in the investigational arm stopped them.
Only one patient in the no-premedication group experienced an iHSR requiring rescue medication after randomisation, giving an estimated reaction rate of 2.3% (95% CI 0.1%-12.3%), compared with 0% (95% CI 0%-7.7%) among patients continuing prophylaxis. The estimated difference in proportions was 2.3% higher in the intervention arm, with a 95% CI of −2% to +7%.
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That patient developed a grade 2 reaction about five minutes into her third weekly paclitaxel dose – her first without premedication – experiencing flushing, back pain, chest tightness, and nausea.
The infusion was stopped and she was treated with intravenous hydrocortisone, diphenhydramine, and famotidine plus fluids.
After her symptoms resolved, paclitaxel was restarted at half the original infusion rate before being increased to the target rate, allowing her to receive the full planned dose.
Premedications were reinstated the following week, although she experienced another, less severe iHSR during that infusion.
She subsequently completed another eight doses with premedication and a graded, rate-escalated infusion without further reactions.
Stopping prophylaxis also appeared to make treatment more tolerable.
Patients who stopped premedications reported significantly lower severity of unwanted appetite increase than those who continued them, with mean symptom scores of 1.0 versus 2.5 on a 0-10 scale (P=0.0018).
Longitudinal analysis also showed significant reductions in trouble sleeping (P=0.002) and unwanted appetite increases (P<0.0001) among patients who stopped prophylaxis. There were no significant differences in drowsiness, nausea, vomiting, heartburn, anxiety, fluid retention, or weight.
Nevertheless, there was a numerical difference in weight: patients continuing prophylaxis gained an average 0.5kg compared with an average 0.3kg loss among those who stopped, although the difference fell short of statistical significance (P=0.06).
The patient-reported data also showed a different pattern for the two key steroid-related symptoms. Sleep problems tended to spike transiently for a night or two following treatments, whereas increased appetite was more persistent among patients continuing prophylaxis.
The researchers said the results affirmed that most patients who tolerated their first two paclitaxel doses with premedication could tolerate later doses without prophylaxis.
“The data from this clinical trial convincingly support that most patients who do not experience an iHSR during the first two doses of paclitaxel (administered with premedications) tolerate subsequent doses well without the need for additional prophylactic premedication,” they wrote.
“Stopping the premedications was associated with reduced toxicity, particularly less trouble sleeping and fewer unwanted increases in appetite.”
None of the patients assigned to stop premedications subsequently asked for them to be reinstated in the absence of a reaction.
Meanwhile, 57% of patients assigned to continue prophylaxis had their dexamethasone dose reduced during subsequent treatments. Among control patients initially receiving diphenhydramine, 71% had their dose reduced, switched from intravenous to oral treatment, or changed to cetirizine – changes the researchers suggested were likely made to improve tolerability.
The researchers acknowledged several limitations, including the single-centre design, relatively small sample, and high dropout before randomisation, largely because of hypersensitivity reactions during the first two paclitaxel doses.
The trial was also not designed as a formal noninferiority study, because the sample size required a sufficiently narrow and clinically meaningful noninferiority margin was considered impractical.
However, the authors said the prospective randomised design was a strength, as was the complete withdrawal of prophylaxis rather than simply dropping dexamethasone.
“The data from our trial, along with our previous studies, strongly support that it is reasonable to discontinue all iHSR premedications after the second paclitaxel dose in patients who have not experienced an iHSR with their first two doses,” they concluded.
“Although a very small percentage of patients may develop a subsequent iHSR, these reactions are generally easy to manage and reversible.
“Stopping unnecessary medications may lessen side effects and burden, while improving chemotherapy unit efficiency.”
Journal of the National Comprehensive Cancer Network, May 2026
