|LETTER TO EDITOR
|Year : 2020 | Volume
| Issue : 2 | Page : 419-420
Kanteti Aditya Pavan Kumar
Department of Medical Oncology, Tata Memorial Hospital, Parel; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
|Date of Submission||05-Jan-2020|
|Date of Acceptance||06-Jan-2020|
|Date of Web Publication||19-Jun-2020|
Kanteti Aditya Pavan Kumar
Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Pavan Kumar KA. Paclitaxel hypersensitivity. Cancer Res Stat Treat 2020;3:419-20
Paclitaxel is an antimicrotubule agent, which interferes with the dynamics of microtubules (irreversibly promotes the assembly and stabilization of microtubules), leading to mitotic block and cell death. One of the important concerns with the administration of paclitaxel is hypersensitivity reaction (HSR), which we recently faced in two of our patients in severe grade.
The HSRs to paclitaxel can be immediate or delayed. Majority of the immediate HSRs occur during the first or second infusion of paclitaxel, and usually develop within minutes of starting the infusion. Complement activation by Cremophor EL (vehicle for paclitaxel), histamine release through a direct but undefined effect of paclitaxel on basophils, and IgE/IgG-mediated mechanism against either paclitaxel or Cremophor EL have been postulated as pathways for immediate hypersensitivity.
Manifestations include dyspnea with/without bronchospasm (81%), urticaria/flushing/rashes (74%), blood pressure changes (decrease – 41%; increase – 15%), and angioedema and associated features (19%). Reactions limited to skin or involving a single organ/system are graded as mild, involvement of two organs/systems as moderate, and involvement of two organs/systems with hypoxia and/or hypotension are graded as severe.
In the initial Phase I study of paclitaxel, severe HSRs occurred in four of the 13 courses when used without premedication. Premedication with dexamethasone and antihistamines (H1 and H2 receptor blockers) dramatically reduced the incidence of HSR. Dexamethasone 20 mg orally 12 hours and 6 hours before, diphenhydramine (or its equivalent) 50 mg 30–60 min before, and cimetidine 300 mg or ranitidine 50 mg 30–60 min before the administration of paclitaxel were the initial recommended prophylactic regimens. Incidence rates for HSR in recent series were in the range of 7%–17% with this prophylactic regimen with 1%–2% of them being severe. With premedication, neither the duration of paclitaxel infusion nor the dose of paclitaxel was shown to influence the incidence of HSR.
A simplified premedication regimen with single dose of dexamethasone (oral or intravenous [iv]) 30–60 min prior, along with other premedication, was shown to be a reasonable alternative by most groups. Recent prospective observational study showed an incidence rate for HSR as low as 1.6% with 1.2% of them being severe with this modified prophylactic regimen. This study represented a real-world report of the use of the modified dexamethasone premedication regimen among Indian patients.
Management of HSR includes stopping further infusion, epinephrine (0.35–0.5 cc iv every 15–20 min until reaction subsides or a total of six doses), diphenhydramine (50 mg), iv fluids, and nebulization with salbutamol. Although corticosteroids have no effect on the initial reaction, they have been shown to block late allergic reactions to a variety of substances. Methylprednisolone 125 mg iv (or equivalent) may be administered to prevent recurrent or ongoing allergic manifestations.
Most patients with paclitaxel hypersensitivity can be re-challenged. High success rate has been demonstrated, using a progressive 24 hours paclitaxel infusion starting at 1–2 mg/hour and slowly increasing the rate to complete the infusion over a period of 24 hours. In a recent study, 75% of patients with paclitaxel HSRs were re-challenged without any desensitization procedure and 91% of them tolerated it without recurrence of HSR. Among five patients with severe reactions, 4 (80%) tolerated re-challenge.
Various desensitization protocols have been described for patients with recurrent infusion reactions despite slower infusion rate and those with positive skin testing. Recently, risk stratification was proposed depending on the severity of the initial HSR and skin testing results to decide on re-challenge versus desensitization to safely allow a significant number of patients to resume regular infusions.
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Conflicts of interest
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