FEATURE ARTICLE

Hypersensitivity Reaction to Paclitaxel:

Nursing Interventions
Jamie S. Myers, RN, MN, AOCN
aclitaxel has been apdexamethasone may be adminproved as second-line
istered as 20 mg orally 12
Paclitaxel, a mitotic inhibitor, is used to treat a vatherapy for recurrent
hours and 6 hours prior to
riety of cancers. A significant incidence of pacliovarian carcinoma (Olson,
therapy. However, recent retaxel-related hypersensitivity reactions (HSRs)
Sood, Sorosky, Anderson, &
search has indicated that a
occurs because of the diluent used. Premedication
Buller, 1998; Physicians Desk
single dose of dexamethasone
Reference [PDR] Nurses
20 mg IV 30 minutes prior to
with dexamethasone, diphenhydramine, and H2Handbook, 1999) and is betherapy is as efficacious as the
histamine antagonists has markedly decreased the
coming the standard of care for
oral regimen for the prevention
incidence of HSRs. Paclitaxel-related HSRs should
first-line therapy in ovarian
of HSRs (Bookman, Kloth,
be managed immediately and appropriately by (a)
cancer when administered in
Kover, Smolinski, & Ozols,
combination with cisplatin or
1997; Markman et al., 1999;
stopping the infusion, (b) administering oxygen,
carboplatin (Olson et al.).
Micha et al., 1998). IV dosing
(c) infusing fluids, (d) continuously monitoring
Paclitaxel also is used in comwith dexamethasone just prior
blood pressure, pulse, and oxygenation, and (e)
bination with other agents to
to treatment has simplified the
treat relapsed or resistant breast
premedication regimen for painitiating standing orders for IV corticosteroids and
cancer and resistant AIDS-retients. Patients may forget to
diphenhydramine or other emergency medications.
lated Kaposis sarcoma. Clinitake one or both doses of the
Oncology nurses are key to the rapid recognition
cal studies are being conducted
oral dexamethasone in preparaand treatment of paclitaxel-related HSRs.
to evaluate its use for advanced
tion for their treatments. Many
head and neck cancer, adenopatients receive paclitaxel in
carcinoma of the upper gastrointestinal the release of chemical mediators (such as combination with more emetogenic agents,
tract, hormone-refractory prostate cancer, histamine) that produce the anaphylactic for which they may receive antiemetic
advanced small cell and non-small cell lung response. Paclitaxel-related HSRs are con- therapy with a 5-HT3 receptor antagonist
cancer, and leukemias (PDR Nurses Hand- sidered to be anaphylactoid rather than (dolasetron, ondansetron, or granisetron).
anaphylactic, as they are not caused by a The addition of IV dexamethasone to a 5book).
specific IgE antibody response to an anti- HT3 receptor antagonist has been to shown
gen. Anaphylactoid reactions are not de- to increase antiemetic efficacy up to 20%
Incidence and Etiology of
pendent on prior exposure to an antigen. (Hesketh et al., 1994).
Paclitaxel-related HSRs occur rapidly,
Hypersensitivity Reactions Rather, the antigen binds to cell surfaces
and causes the direct release of inflamma- typically during the first 10 minutes to an
A significant incidence of hypersensi- tory mediators. The resultant clinical hour of the infusion (Peereboom et al.,
tivity reactions (HSRs) has been associ- manifestations are identical to an anaphy- 1993; Rowinsky & Donehower, 1995).
ated with paclitaxel. HSRs first were lactic reaction (Craig & Capizzi, 1985; Signs and symptoms may include any or all
observed during phase I clinical trials. Labovich, 1999). Paclitaxel is prepared in of the following: respiratory distress, hyPrior to the advent of premedications, the a diluent made up of polyoxyethylated potension, angioedema, flushing with
incidence was estimated as high as 10% castor oil (Cremophor El, BASF Aktien- urticaria, bronchospasm, diaphoresis, hy16% and currently is estimated to be 1% gesellschaft, Ludwigschafen, Germany) pertension, and chest or back pain (Olson et
3% (Olson et al; 1998; Rowinsky & Done- that is responsible for the histamine re- al., 1998; Peereboom et al.; Weiss, 1992).
lease and HSRs in the majority of cases
hower, 1995; Weiss, 1992).
Most chemotherapy-induced HSRs are (Olson et al., 1998).
Premedication has markedly decreased Submitted November 1999. Accepted for
type I reactions. Type I reactions occur because initial exposure to the antigen stimu- the incidence of paclitaxel-related HSRs. A publication January 3, 2000. (Mention of spelates the formation of specific IgE antibod- commonly used premedication regimen in- cific products and opinions related to those
ies that attach to receptors on basophils cludes dexamethasone, diphenhydramine, products do not indicate or imply endorseand mast cells. Upon subsequent exposure and an H2-histamine antagonist such as ment by the Clinical Journal of Oncology
to the antigen, the IgE antibodies trigger cimetidine, ranitidine, or famotidine. The Nursing or the Oncology Nursing Society.

CLINICAL JOURNAL OF ONCOLOGY NURSING VOLUME 4, NUMBER 4 HYPERSENSITIVITY REACTION TO PACLITAXEL

161

Facial flushing alone is not an indication for

stopping the infusion.
Because of the incidence of paclitaxelrelated HSRs and the fact that they tend to
occur early during the infusion, most institutions have very specific standards for the
monitoring of vital signs (see Figure 1).
Because most paclitaxel-related HSRs occur during the first or second dose, some
institutions alter vital sign monitoring for
subsequent doses if the patient tolerates
the first one to two infusions well. One institution has treated more than 1,100
patients with one-hour paclitaxel infusions
(Sarah Cannon Cancer Center in Nashville, TN). Researchers there recommend
taking baseline vital signs and continuously monitoring the patient for the first
10 minutes of the infusion. Vital signs are
repeated if the patient becomes symptomatic (Greco, Thomas, & Hainsworth,
1999). Using a continuous blood pressure
monitoring device that can be set at specific time intervals may be helpful. These
devices also may be equipped with oxygen
saturation monitoring capabilities. In the
event of an HSR, oxygen saturation is a
valuable assessment tool, as dyspnea and
bronchospasm may be severe.

Nursing Interventions
In the event of a paclitaxel-related HSR,
the nurse should stop the infusion immediately and continue to administer IV fluids to
maintain blood pressure. Oxygen should be
administered to counteract shortness of
breath and decreased oxygen saturation.
Not all facility protocols specify the drugs
of choice to treat the symptoms of HSR.
Most recommend having emergency drugs
available in the event of a reaction. The literature states that the most commonly used
drugs are epinephrine, antihistamines, and
corticosteroids. (Compton, 1997; Craig &
Capizzi, 1985; Labovich, 1999; Mackan,
1995). Because of the potential rapidity and
severity of paclitaxel-related reactions, having standing orders for the agents to be
administered is ideal (see Figure 2). This allows the interventions to proceed while the

Every 5 minutes x 3 (or continuous observation for the first 15 minutes)

Every 15 minutes x 2
Then hourly (Decrease to every 4 hours for
24-hour infusions.)

FIGURE 1. SAMPLE VITAL SIGN MONITORING

GUIDELINE FOR PACLITAXEL INFUSION
Note. Based on information from Greco et al.,
1999; Labovich, 1999.

162

Stop paclitaxel infusion.

Infuse normal saline at 200 cc/hour until blood pressure stabilizes.
Administer oxygen at two to four liters per nasal cannula to maintain oxygenation.
Administer methylprednisolone 125 mg IV push to counteract respiratory distress.
Administer diphenhydramine 50 mg IV push to counteract respiratory distress and inflammation.
Continuously monitor blood pressure, pulse, and oxygen saturation.
Notify physician immediately for further orders.
Initiate a code if airway patency is not maintained or cardiopulmonary arrest occurs.

FIGURE 2. SAMPLE STANDING ORDERS FOR PACLITAXEL-RELATED HYPERSENSITIVITY REACTIONS

Note. Based on information from Craig & Capizzi, 1985; Labovich, 1999; Weiss, 1990.

physician is being notified and may decrease the need for intubation.

Current Literature on
Rechallenge
The literature supports rechallenging a
patient who has had a paclitaxel-related
HSR. Studies of paclitaxel rechallenge are
being conducted because a survival advantage exists with the use of paclitaxel for
women with advanced ovarian cancer as
compared to other regimens (McGuire et
al., 1996). The first publication of research
results (Peereboom et al., 1993) described
the successful retreatment of eight patients
who had major paclitaxel-related HSRs.
The patients were rechallenged within hours
to days with fresh solutions of paclitaxel at
full doses. Premedication regimens included
up to four doses of corticosteroids (typically
dexamethasone 20 mg IV every six hours)
as well as IV diphenhydramine and an H2histamine antagonist 30 minutes prior to
therapy. Initial infusion rates were 10%
25% of the 24-hour infusion rate. This rate
was maintained for 12 hours and then
gradually increased over the next 36 hours
to equal a 24-hour infusion rate. Two patients had minor facial flushing that did not
require intervention. One patient experienced a mild rash. One patient who had experienced severe chest pain during HSR had
mild, transient chest pain during the rechallenge.
A retrospective study was published recently for six patients who were rechallenged after experiencing paclitaxel-related HSRs (Olson et al., 1998). The recommendations from this study were to
stabilize the patient and remedicate with
dexamethasone 20 mg IV, diphenhydramine 50 mg, and cimetidine 300 mg
IV. Thirty minutes following premedication, paclitaxel (using the original solution) was reinitiated at 12 mg per hour.
The rate was increased gradually over the
next 46 hours until a 24-hour rate was
obtained. Six of seven women were retreated successfully without complica-

tions. One woman refused retreatment

over 24 hours. A three-hour retreatment
was attempted, but she experienced a second severe HSR, requiring admission to
the intensive-care unit.
Additional research is needed before
rechallenge becomes the standard of care.
To date, the sample sizes have been small.
If rechallenge is being considered, it
should not be attempted in a setting that is
not equipped to handle respiratory and circulatory emergencies.

Current Literature on
Rates of Infusion
Several recent studies discuss the safety
of one-hour paclitaxel infusions (Greco et
al., 1999; Hainsworth, Raefsky, & Greco,
1995; Seidman et al., 1998). Both one- and
three-hour paclitaxel infusions have been
shown to be safe with no increase in the
incidence of HSRs. Patients with a history
of recent myocardial infarction, seconddegree or higher heart block, congestive
heart failure, or other contraindication to
excess fluid overload may be treated more
safely with a three-hour infusion (Greco et
al.). Myelosuppression is less severe with
the shorter infusions as compared to 24hour infusions. Peripheral neuropathy occurs with more frequency (Greco et al.).
One study evaluated the safety of paclitaxel infusions given in less than one hour
(Tsavaris & Kosmas, 1998). Paclitaxel at a
dose of 175 mg/m2 in 150 ml of normal saline was administered to four patients who
had received at least two prior cycles of
paclitaxel without HSRs. All four patients
experienced angioedema, sinus tachycardia, dyspnea, and diaphoresis within 515
minutes of beginning the paclitaxel infusion. Three patients also experienced generalized edema. The paclitaxel infusions
were stopped, and the patients were medicated with dimethindene maleate, ranitidine, and methylprednisolone. All symptoms resolved within 1530 minutes, and
the patients were successfully retreated
with the one-hour rate. The study con-

JULY/AUGUST 2000 VOLUME 4, NUMBER 4 CLINICAL JOURNAL OF ONCOLOGY NURSING

cluded that paclitaxel infusions of less

than one hour cannot be recommended.

type I HSRs and are instrumental in detecting these reactions early and intervening
quickly and appropriately.

Nursing Role

References

The role of the oncology nurse is key to

early identification and management of
paclitaxel-related reactions. Appropriate
monitoring of vital signs and prompt initiation of interventions are vital to a positive patient outcome. In addition, the oncology nursing role includes patient/
family education about the medication and
potential for side effects and toxicities. In
the event that a reaction does occur, calm
reassurance to the patient and family while
interventions are efficiently administered
can make a difference in their anxiety
level and perception of the event. Careful
documentation is necessary for an accurate
medical record. The physician will consider the severity of the HSR when
determining whether to rechallenge the
patient after his or her condition stabilizes.
In the event that the physician wants to
rechallenge the patient with paclitaxel, education and reassurance are acutely necessary to help put the patient and family at
ease with the treatment plan. Patients and
families must be assured of the constant
surveillance of the nursing staff during the
initial 1560 minutes of the infusion. They
should be informed of the immediate availability of medications to treat any signs and
symptoms that they may experience. They
should be encouraged to discuss any issues
of concern about the treatment plan with the
oncology nurse and the physician prior to
giving consent to proceed.
Although premedication with dexamethasone, diphenhydramine, and H2-histamine antagonists has greatly decreased
the incidence of HSRs to paclitaxel, they
still have the potential to occur. Oncology
nurses play a major role in the prevention of

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Author Contact: Jamie S. Myers, RN,

MN, AOCN, can be reached at Research
Medical Center, c/o 7 East Oncology, 2316
East Meyer Boulevard, Kansas City, MO
64132 or at jsmyers@healthmidwest.org.

Rapid Recap
Hypersensitivity Reaction to Paclitaxel: Nursing Interventions
Without appropriate premedication, a significant incidence of paclitaxel-related hypersensitivity reactions (HSRs)
occurs.
Dexamethasone may be given as an oral or IV premedication regimen along with IV diphenhydramine, an H2-histamine antagonist, and an antiemetic.
Close monitoring of blood pressure, pulse, and oxygenation is important during initial doses of paclitaxel, particularly
during the first 15 minutes of infusion.
The availability of standing orders for the administration of emergency medications, such as methylprednisolone,
diphenhydramine, and epinephrine, should be a standard of care for patients receiving paclitaxel.
The literature supports the rechallenging of paclitaxel in patients who have experienced an HSR.
Oncology nurses are key to the rapid recognition and treatment of paclitaxel-related HSRs.

CLINICAL JOURNAL OF ONCOLOGY NURSING VOLUME 4, NUMBER 4 HYPERSENSITIVITY REACTION TO PACLITAXEL

163

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