Severe anaphylaxis caused by intravenous anti‐cancer drugs

Abstract

Background The incidence and risk factors of severe anaphylaxis by intravenous anti‐cancer drugs are unclear, whereas those of milder reactions have been reported. Study Design Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non‐epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). Results Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person‐day anti‐cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person‐based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%–0.67%) and the administration‐based incidence was 0.031% (27/88,200, 95% CI 0.019%–0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin‐induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%–13.1%). Carboplatin caused severe anaphylaxis after at least 9‐min interval since the drip started. Thirteen out of 14 patients experienced carboplatin‐induced severe anaphylaxis within a 75‐day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life‐long incidence of 0.93% (9/968, 95% CI 0.27%–1.59%). Conclusion We elucidated the high‐risk settings of chemotherapy‐induced severe anaphylaxis.

Allergy testing for Cremophor in a patient with cervical cancer with infusion reactions to paclitaxel and docetaxel

“…In fact, Kim et al reported an outbreak of severe allergies requiring endotracheal intubation due to a multivitamin supplement containing Cremophor 11. In a retrospective review, the incidence of anaphylaxis with phytonadione (vitamin K1), including Cremophor, was estimated to be 3 cases per 10 000 doses (0.03%),12 and severe allergic reactions to paclitaxel occurred in 9 out of 8894 patients (1%) 13. In clinical practice, it is estimated that 3% (0.03%/1%) of severe anaphylaxis occurrences during paclitaxel administration may be due to allergy to Cremophor.…”

Changing patterns in the epidemiology of drug allergy

“…Reactions to paclitaxel occur in up to 40% of patients without anti‐histamine and steroids premedication and in 1.5% of pre‐medicated patients 133 . The rate of reactions after multiple exposures is 10.7%–18.9% for oxaliplatin, 12%–44% for carboplatin, and 5%–20% to cisplatin 133,135–138 . The rate of carboplatin HSR increases from 1% during the first six cycles to 27% after >6 cycles and sooner for BRCA mutations carriers 51,136,139 …”

“…In countries such as Germany, mAbs contributes to the top 10 drugs inducing anaphylaxis, 140 which may be related to drug usage patterns and genetic effects. The rate of reactions has been reported as 5%–10% for rituximab; 2%–3% for infliximab; 3%–22% for cetuximab; and 0.6%–5% for trastuzumab 133,135–138 . Risk factors for HSRs to biological agents include the underlying disease, the patient's immune status, degree of humanization, glycosylation pattern, type of sourcing cells, dosing interval, and excipients.…”

“…133 The rate of reactions after multiple exposures is 10.7%-18.9% for oxaliplatin, 12%-44% for carboplatin, and 5%-20% to cisplatin. 133,[135][136][137][138] The rate of carboplatin HSR increases from 1% during the first six cycles to 27% after >6 cycles and sooner for BRCA mutations carriers. 51,136,139…”

“…The rate of reactions has been reported as 5%-10% for rituximab; 2%-3% for infliximab; 3%-22% for cetuximab; and 0.6%-5% for trastuzumab. 133,[135][136][137][138] Risk factors for HSRs to biological agents include the underlying disease, the patient's immune status, degree of humanization, glycosylation pattern, type of sourcing cells, dosing interval, and excipients. Patients with anti-drug antibodies are more likely to develop DA.…”