Reducing paclitaxel hypersensitivity reactions in gynecologic oncology patients (521)

Objectives: In the year 2020, paclitaxel hypersensitivity reaction (HSR) rates differed between the chemotherapeutic administration sites within our division (Site 1: 14.4%, 38/264 patients; Site 2: 4.4%, 2/46 patients). The paclitaxel pre-medication regimen at both sites includes dexamethasone 10mg IV and famotidine 20mg IV. However, diphenhydramine 25mg is given orally at site 1 and IV at site 2. We aimed to reduce the HSR rate at site 1 by changing the administration of diphenhydramine from oral to IV. Methods: All paclitaxel-containing gynecologic oncology treatment plans were identified in the electronic medical record (EMR) at sites 1 and 2. Site 1 paclitaxel pre-medication plans were altered to include IV diphenhydramine, which became active on April 15, 2021. EMR review was performed to identify HSRs from April 15, 2021, to September 15, 2021. The primary outcome was the incidence of HSR after pre-medication standardization. Secondary outcomes included frequency of severe HSR, frequency of successful completion of paclitaxel infusion, and assessment of post-HSR management strategies within the division. Descriptive statistics were performed in addition to Chi-square tests. Results: A total of 149 patients received paclitaxel during cycle 1 or 2 (Site 1: 125; Site 2: 24). On average, 2.1 medication allergies per patient were documented. Patients predominantly had an ovarian/ fallopian tube/primary peritoneal cancer (48%) or endometrial cancer (41%); 72% of patients had stage III or IV disease. Seventy- three percent received carboplatin/paclitaxel; 30% in the neoadjuvant setting, 40% in the adjuvant setting, and 30% for recurrent disease. Fifteen percent had received paclitaxel previously. HSR rate per person was 11.2% (14/125) at site 1 and 12.5% (3/24) at site 2, reflecting a 22% reduction in HSR for site 1 (p=0.44) after the intervention. Ninety-four percent of HSRs occurred during cycle 1, and all reactions were moderate (29%) to severe (71%) in nature by the standardized Common Terminology Criteria for Adverse Events. No patients who experienced an HSR had previously received paclitaxel; 59% of patients were re-challenged with paclitaxel the same day as their HSR with 100% success. For the subsequent cycle, 59% (10/17) of patients had their chemotherapy regimen altered (8/10 to docetaxel, 2/10 to doxorubicin) and 18% (3/17) had their pre-medication regimen altered. Of the patients who experienced a severe HSR, 67% (8/12) were changed to an alternative chemotherapy regimen and 17% (2/12) were re-challenged with paclitaxel. 18% (3/17) of patients who experienced a paclitaxel HSR subsequently had an HSR to another agent; no repeat HSRs to paclitaxel occurred. Conclusions: Standardization of the pre-medication regimen between chemotherapy sites reduced the paclitaxel HSR rate at site 1 by 22%. Continued optimization of the paclitaxel pre-medication regimen will be needed to achieve a statistically significant reduction in HSR. Though HSRs can be distressing to patients, our data suggest that same-day re-challenge is successful in the vast majority of patients, and re-titration should be considered. Objectives: In the year 2020, paclitaxel hypersensitivity reaction (HSR) rates differed between the chemotherapeutic administration sites within our division (Site 1: 14.4%, 38/264 patients; Site 2: 4.4%, 2/46 patients). The paclitaxel pre-medication regimen at both sites includes dexamethasone 10mg IV and famotidine 20mg IV. However, diphenhydramine 25mg is given orally at site 1 and IV at site 2. We aimed to reduce the HSR rate at site 1 by changing the administration of diphenhydramine from oral to IV. Methods: All paclitaxel-containing gynecologic oncology treatment plans were identified in the electronic medical record (EMR) at sites 1 and 2. Site 1 paclitaxel pre-medication plans were altered to include IV diphenhydramine, which became active on April 15, 2021. EMR review was performed to identify HSRs from April 15, 2021, to September 15, 2021. The primary outcome was the incidence of HSR after pre-medication standardization. Secondary outcomes included frequency of severe HSR, frequency of successful completion of paclitaxel infusion, and assessment of post-HSR management strategies within the division. Descriptive statistics were performed in addition to Chi-square tests. Results: A total of 149 patients received paclitaxel during cycle 1 or 2 (Site 1: 125; Site 2: 24). On average, 2.1 medication allergies per patient were documented. Patients predominantly had an ovarian/ fallopian tube/primary peritoneal cancer (48%) or endometrial cancer (41%); 72% of patients had stage III or IV disease. Seventy- three percent received carboplatin/paclitaxel; 30% in the neoadjuvant setting, 40% in the adjuvant setting, and 30% for recurrent disease. Fifteen percent had received paclitaxel previously. HSR rate per person was 11.2% (14/125) at site 1 and 12.5% (3/24) at site 2, reflecting a 22% reduction in HSR for site 1 (p=0.44) after the intervention. Ninety-four percent of HSRs occurred during cycle 1, and all reactions were moderate (29%) to severe (71%) in nature by the standardized Common Terminology Criteria for Adverse Events. No patients who experienced an HSR had previously received paclitaxel; 59% of patients were re-challenged with paclitaxel the same day as their HSR with 100% success. For the subsequent cycle, 59% (10/17) of patients had their chemotherapy regimen altered (8/10 to docetaxel, 2/10 to doxorubicin) and 18% (3/17) had their pre-medication regimen altered. Of the patients who experienced a severe HSR, 67% (8/12) were changed to an alternative chemotherapy regimen and 17% (2/12) were re-challenged with paclitaxel. 18% (3/17) of patients who experienced a paclitaxel HSR subsequently had an HSR to another agent; no repeat HSRs to paclitaxel occurred. Conclusions: Standardization of the pre-medication regimen between chemotherapy sites reduced the paclitaxel HSR rate at site 1 by 22%. Continued optimization of the paclitaxel pre-medication regimen will be needed to achieve a statistically significant reduction in HSR. Though HSRs can be distressing to patients, our data suggest that same-day re-challenge is successful in the vast majority of patients, and re-titration should be considered.