Paclitaxel Hypersensitivity: Is Titrated Dosing in Gynecologic Oncology Patients Necessary?

TL;DR

Stopping titrated paclitaxel dosing in gynecologic cancer patients led to more and more severe hypersensitivity reactions, especially during the second treatment.

Contribution

This study shows that eliminating titrated paclitaxel dosing increases hypersensitivity risks in gynecologic oncology patients.

Findings

Non-titrated paclitaxel infusions had a 20.8% hypersensitivity reaction rate compared to 11.9% for titrated infusions.

Second infusions with non-titrated paclitaxel had a 22.4% hypersensitivity rate, significantly higher than titrated infusions.

Non-titrated infusions were associated with higher-grade hypersensitivity reactions.

Abstract

Paclitaxel is one of the most widely used chemotherapeutic agents for treatment of gynecologic malignancies, but a standard titration and administration protocol does not exist. Our institution performed titrated dosing of the first two lifetime paclitaxel treatments due to concern for hypersensitivity reactions (HSRs), but transitioned to non-titrated dosing in April 2023. We observed an increase in HSR incidence associated with cessation of paclitaxel titration—specifically during the second lifetime administration—and grade of reactions were observed to be higher as well.

Background/Objectives: After several decades of using titrated paclitaxel infusions, our institution adopted non-titrated infusions in April 2023 to streamline infusion workflows. We aimed to evaluate whether this alteration in infusion was associated with a higher incidence of HSRs. Methods: This was a retrospective cohort study of patients receiving paclitaxel with titration versus non-titration from April 2022 through November 2023. Patients diagnosed with gynecologic cancers who presented for their first or second paclitaxel lifetime infusions were included. Results: A total of 150 patients were included in this study, each with one or two infusions, for a total of 282 infusion visits. There were 176 infusions performed with titrated paclitaxel (62.4%), and 106 infusions performed with non-titrated paclitaxel dose (37.6%). HSRs occurred in 20.8% of the non-titrated paclitaxel infusions and in 11.9% of titrated paclitaxel infusions (RR 1.73 (95% CI 1.006–3.006), p = 0.047). Additionally, when stratifying by first- or second-visit infusions, the HSR rate increased significantly for non-titrated infusions to 22.4% during the second visit, while there was a decrease to 8.4% for titrated infusions (RR 2.66 (95% CI 1.105–6.413), p = 0.029). Non-titrated infusion reactions were associated with higher grades of reaction. Conclusions: HSRs occurred more frequently with non-titrated infusions, particularly during the second administration, suggesting that eliminating titration may increase hypersensitivity risk. These findings support a prospective evaluation of titration rates to further refine paclitaxel administration.