Prevention of HSRs
To reduce the risk of HSRs with taxane therapy, premedication with both H1- and H2-receptor antagonists, as well as a corticosteroid may be required; however, these do not eliminate the risk of HSRs entirely.r
The following schedules are suggested premedication regimens for taxane therapy:
Premedication for nab-paclitaxel
Premedication is generally not required for nab-paclitaxel, but may be needed in patients with prior mild to moderate HSRs.r
Premedication for paclitaxel
Paclitaxel is administered either weekly, every two weeks or every three weeks, alone or in combination with other agents.r
Recent studies have demonstrated that addition of H2 antagonists to combination of H1 antagonist and corticosteroid confers no additional benefit in reducing the incidence and severity of HSRs associated with paclitaxel treatment. This warrants withdrawal of H2 antagonists from the premedication regimens for paclitaxel treatment.rrr
The following premedication regimens are suggested, based on the frequency of paclitaxel dosing. Stopping premedication for paclitaxel can be considered in patients who have not experienced an HSR in the first 2 doses:rrr
Weekly paclitaxel reducing premedication regimen
For paclitaxel premedication, the product information recommends a higher dose of dexamethasone than outlined below; however, due to the potential for cushingoid changes and other complications, many centres use a reducing regimen with an anecdotally acceptable rate of HSRs.r
Week 1:
Dexamethasone 8 mg PO, 60 minutes prior to paclitaxel, plus
Loratadine 10 mg PO, 60 minutes prior to paclitaxel.
Week 2:
Dexamethasone 4 mg PO, 60 minutes prior to paclitaxel, plus
Loratadine 10 mg PO, 60 minutes prior to paclitaxel.
Week 3 and 4:
Loratadine 10 mg PO, 60 minutes prior to paclitaxel.
Week 5: no further premedication
When using the above regimen, if the patient has an HSR on week 1, the dose of dexamethasone may need to be increased as follows:
Dexamethasone 20 mg PO, the night before and morning of paclitaxel, plus
Loratadine 10 mg PO, 60 minutes prior to paclitaxel.
If no further HSR occurs, the premedication may be reduced as above. Should the patient have a severe or further HSR, it may not be feasible to reduce the premedication doses. If the patient continues to be treated with paclitaxel despite mild HSRs, a standard full dose premedication should be given.
Two-weekly (dose dense) or three-weekly paclitaxel premedication regimen
For patients who are undergoing paclitaxel treatment on a two-weekly or three-weekly schedule, the following premedication regimen is suggested before each treatment cycle:r
Dexamethasone 20 mg IV, 30 minutes prior to paclitaxel, plus
Loratadine 10 mg PO, 60 minutes prior to paclitaxel.
An alternate premedication regimen, below, may also be considered:
Dexamethasone 20 mg PO, the day before and morning of paclitaxel, plus
Loratadine 10 mg PO, 60 minutes prior to paclitaxel.
Premedication for docetaxel
Due to lower incidence and severity of docetaxel HSRs after steroid treatment, histamine antagonists are not routinely given as premedication, however some clinicians still choose to administer a H1-antagonist such as loratadine 10 mg PO, 60 minutes prior to the docetaxel infusion. The following dose of dexamethasone is recommended before each treatment cycle:r
Three-weekly docetaxel premedication regimen
For three-weekly docetaxel, premedicate using dexamethasone 8 mg PO, TWICE a day for 3 consecutive days, commencing one day prior to docetaxel administration.r# This reduces the severity and incidence of fluid retention associated with docetaxel, and the severity of HSRs.
#For patients being treated for prostate cancer with concurrent prednisone, instead give dexamethasone 8 mg at 12 hours, 3 hours and 1 hour prior to docetaxel administration.
Please refer to the specific eviQ protocols for the suggested dexamethasone premedication for these treatments.
There is also evidence in the literature that a single dose of dexamethasone 20 mg IV, administered prior to docetaxel on the day of treatment, results in an acceptable rate of HSRs.r This is therefore an alternative premedication regimen, particularly in cases where patients are non-compliant with their oral premedication.
Weekly docetaxel premedication regimen
For patients on a weekly docetaxel regimen, a single dose of dexamethasone 8 mg PO on the morning of chemotherapy is recommended.
Premedication regimen for cabazitaxel
For patients undergoing treatment with cabazitaxel, premedicate using a corticosteroid, H1- and H2-receptor antagonist. The following premedication regimen should be given before each treatment cycle:
Oral:
Dexamethasone 8 mg PO, 60 minutes prior to cabazitaxel, plus
Ranitidine* 150 mg PO, 60 minutes prior to cabazitaxel, plus
Loratadine 10 mg PO, 60 minutes prior to cabazitaxel.
IV:
Dexamethasone 8 mg IV, 30 minutes prior to cabazitaxel, plus
Ranitidine* 50 mg IV, 30 to 60 minutes prior to cabazitaxel, plus
Loratadine 10 mg PO, 60 minutes prior to cabazitaxel
*Ranitidine can be replaced by an equivalent H2 receptor antagonist. It is the consensus of the medical oncology reference committee that H2 antagonist may be omitted in clinical practice, however there is no published evidence available. Clinical judgement should include assessment and monitoring of individual patients, institutional policy and availability of alternative drugs.
H2 receptor antagonists
| Name |
Formulations |
Time of peak plasma level |
Evidence of use in taxane induced HSR prophylaxis |
| Ranitidine |
Tablet, oral liquid, injection |
Oral 1-3 hours/injection data not available |
Ranitidine 50 mg IV or 150 mg PO, 30-60 min before cabazitaxelr |
| Famotidine |
Tablet |
1-3 hours |
Famotidine 20 mg PO/IV, 30-60 min before cabazitaxelr |
Treatment
Emergency treatment (e.g. adrenaline, antihistamine and corticosteroid) for severe HSR must be readily available during taxane administration.r
If a patient develops an HSR, treatment should be stopped immediately and the symptoms treated with appropriate medication, for example, antihistamines, corticosteroids, bronchodilators and/or oxygen.r
In many cases, a mild to moderate reaction will resolve after medication and a brief interruption of treatment. However, re-challenge can have potentially serious consequences, therefore administration of additional premedication, reducing the infusion rate and close monitoring during the next administration of the taxane is essential.rrr
In the case of a severe reaction, taxane treatment should not be continued.r
If the HSR presents as anaphylaxis, treat as per emergency procedure. Delays in emergency treatment are associated with an increased mortality rate.r
Switching taxanes
There have been multiple case reports of patients who, after experiencing an HSR to one taxane, have been successfully treated with another. However, cross-reactivity between agents can occur, and substitution should be performed with caution.r Reports in the literature have described substitution of paclitaxel with docetaxel, docetaxel with paclitaxel, and both docetaxel and paclitaxel with nab-paclitaxel.rrrr
Drug desensitisation
Drug desensitisation may be an option for patients where there is no alternative therapy available. Desensitisation involves readministration of the taxane using a series of sequential steps in which the dose is gradually increased. Because a desensitisation protocol induces only a temporary tolerance, it must be carried out every time the patient receives treatment.rrr It is good practice to counsel patients that they remain allergic to the drug and must be desensitised for each subsequent administration.
Refer to institutional policy for specific desensitisation protocols used in your institution.