Adding IV hydrocortisone (HCT) to standard dexamethasone (DXM) prophylaxis reduced the incidence of hypersensitivity reactions (HSR) in women undergoing paclitaxel-based treatment for gynecologic cancers.
Over 405 cycles of paclitaxel, investigators observed just 1 (0.5%) incidence of HSR among women assigned to HCT compared with 9 cases (4.2%) in women assigned to dexamethasone alone (P
= .022). HSR was also more severe in women in the standard arm. Investigators observed 3 grade 1 HSRs and 6 grade 2 HSRs with DXM only, compared with a single grade 2 HSR in the HCT group. There was also a single incident of a grade 3 HSR in the HCT group who mistakenly did not receive treatment.
The overall probability of experiencing HSR during any of up to 6 cycles of paclitaxel infusion was 12%. Patients in the standard group were nearly 9 times more likely to experience HSR (18% vs 2.4%; P
“Despite observation of a modest number of 86 gynecologic cancer patients undergoing just a few hundred cycles (405) of paclitaxel chemotherapy, it was somewhat surprising how the addition of IV HCT (100 mg) to routine prophylaxis by DXM (20 mg) and H1 and H2 antagonists almost completely eliminated the HSRs often observed with this therapy,” wrote co-investigators Dhammapoj Jeerakornpassawat, MD, and Prapaporn Suprasert, MD, with Thailand’s Chiang Mai University.
All HSRs occurred within the first 3 of the 6 cycles studied and always within the first 40 minutes of infusions that usually last for 3 hours.
Hypersensitivity reaction symptoms included facial flushing (8), dyspnea (7), palmar rash (1), and transient hypotension (1).
There were 23 incidences in the DXM-HCT group in which the patient was erroneously not given her dose of HCT. These 23 cycles were excluded from per-protocol analysis, leaving 192 cycles in the DXM plus HCT group and 213 cycles in the DXM group.
HSR is a common adverse event associated with paclitaxel treatment, and 10.6% of cases are classified as severe. HSRs usually occur in the first cycle of infusion.
To prevent such HSRs, patients are usually premedicated with steroidal drugs (often 20 mg of dexamethasone) or with an H1 antagonist combined with an H2 antagonist. Prophylactic treatment has been found to cut the rate of severe paclitaxel HSRs to 1.3%, although incidence of mild reactions remained high at approximately 20%.
HCT, a less powerful steroid, is widely used to treat acute allergic reactions, such as severe asthma and anaphylaxis, because it has an immediate onset of action and a half-life of 6 to 12 hours. Investigators conducted this study combining the greater potency of DXM with the faster effect of HCT to determine if combination could reduce the incidence of paclitaxel HSRs.
Patients were recruited from June 2015 through June 2016, and there were 45 patients in both groups.
During paclitaxel infusion, clinic nurses observed the patients and measured vital signs every 15 minutes during the first hour and every 30 minutes afterward until completion of both paclitaxel and platinum infusions. If any HSRs occurred during paclitaxel infusions or in the interval before platinum infusion, the nurse recorded and graded them from 1 to 5 for severity. Upon detection of any HSRs, paclitaxel infusion was stopped, the doctor notified, and standard treatment for HSR implemented. Paclitaxel infusion resumed once HSR symptoms were sufficiently resolved.
Patients discontinued treatment if they manifested paclitaxel HSRs of grade ≥3 or stopped receiving paclitaxel because of intentional change of chemotherapy regimen for clinical reasons such as tumor nonresponse.
Jeerakornpassawat D, Suprasert P. Randomized, controlled trial of dexamethasone versus dexamethasone plus hydrocortisone as prophylaxis for hypersensitivity reactions due to paclitaxel treatment for gynecologic cancer. Int J Gynecol Cancer. Int J Gynecol Cancer. 2017;27(8):1794-1801 doi: 10.1097/IGC.0000000000001069.