Taxanes often are one of the first classes of chemotherapeutic drugs mentioned with regard to chemotherapy and HSRs. The incidence rate for HSRs with paclitaxel and docetaxel ranges from 2% to 4% with appropriate premedication (Shepherd, 2003). The excipients in which these chemotherapeutic drugs are dissolved are thought to be the likely culprits in taxane-related HSRs. Cremophor EL is used to formulate paclitaxel, and polysorbate 80 (Tween 80) is the diluent for docetaxel. ONS guidelines recommend premedication for paclitaxel and docetaxel as follows:

As mentioned, even with appropriate premedication, HSRs can occur. In these cases, the patient and medical staff need to discuss whether rechallenge is appropriate (i.e., infusing the same or a similar compound after an HSR, usually with additional drugs used in the premedication regimen). It is important to note that a patient who has a reaction to one of the taxanes is not any more likely to react to the other (Gobel, 2005). Increasing the infusion time or titrating the start of these medications may aid successful desensitization.

Platinum-induced HSRs tend to occur in heavily pretreated patients. Platinum compounds as a group are associated with an HSR incidence rate of 10% to 27% (Gobel, 2005). The success rate for rechallenge varies and likely depends on the premedication regimen, time of infusion, and concentration of the agent.

Although carboplatin is used in a variety of patient populations, most research related to HSRs is reported in the gynecologic oncology literature (typically patients with ovarian carcinoma). Studies report an HSR incidence rate of 5% to 34% in this patient population (Dizon et al., 2002). A significant point of interest with carboplatin HSRs is that they are far more likely to occur after at least 6 cycles of the drug (Markman et al., 2004; Jones et al., 2003; Rose et al., 2003), which suggests that sensitization to the agent plays a role in the development of the reaction. Some studies report that reactions can occur within minutes of administration, but they also can occur days after the exposure (Dizon et al., 2002). Other studies state that HSRs to carboplatin usually occur after approximately 50% of the agent has been administered (Rose et al., 2003; Markman et al., 1999).

Most of the literature describing rechallenges involves patients with documented HSRs to carboplatin. One study describes a successful crossover rechallenge with cisplatin in 5 of 7 (71%) patients who initially developed HSRs to carboplatin (Dizon et al., 2002). A similar crossover study reports an initial successful rechallenge in five patients after full desensitization. The desensitization protocol included daily dexamethasone and diphenhydramine for 4 days before the day of treatment; diphenhydramine on the morning of treatment; an intradermal skin test; premedication with ranitidine, dexamethasone, and ondansetron; and then a titrated schedule of cisplatin (starting at 50 mL of {1/1000} of a full dose of the drug over 30 minutes and subsequently increasing the concentration while reducing the infusion time) (Jones et al., 2003). Later cycles ultimately were discontinued because three patients had disease progression and two developed HSRs (Jones et al., 2003).

Another study reported an 88% success rate (29 of 33 patients) on initial rechallenge with the same agent (carboplatin) (Rose et al., 2003). This prolonged desensitization protocol, as detailed by Rose and colleagues (2003), involved a 15- to 16-hour gradually increase in the concentration of the chemotherapeutic agent, with premedication. However, three more patients (of the initial 29 who were successfully rechallenged) developed HSRs to carboplatin during subsequent cycles 2 through 6 (Rose et al., 2003).

Markman and colleagues (2003a) found that intradermal skin testing (at initiation of second-line therapy/cycle 6 and above) may help predict the probability that a patient will not react to carboplatin. They stated, “A negative carboplatin skin test seems to predict with reasonable reliability for the absence of a severe hypersensitivity reaction with the subsequent drug infusion. The implications of a positive test remain less certain.” The authors also reported a 1.5% false positive rate. In another study, Markman and coworkers (2004) built on previous research and developed a novel desensitization strategy for patients with positive skin tests or documented HSRs to carboplatin. Theorizing that the underlying mechanisms responsible for the carboplatin-related HSRs are complex and multifactorial, the authors developed a multipronged approach. Cisplatin was substituted for carboplatin for most of the patients with positive skin test results to carboplatin. Patients also received an extensive multidrug premedication regimen aimed at preventing an HSR. The drugs used for premedication included oral prednisone, histamine receptor antagonists (H₁ and H₂ blockers), indomethacin, albuterol sulfate, montelukast, Zileuton, diphenhydramine, and dexamethasone. Skin testing with cisplatin or carboplatin was done immediately before infusion of the first dilution of the agent. Then, escalating concentrations of cisplatin or carboplatin were infused. Four of the five patients in the study were successfully rechallenged. One patient had a positive skin test result immediately before the infusion and therefore was not rechallenged.

Although carboplatin is the platinum agent of choice in most circumstances because of its greater efficacy and more desirable side effect profile, cisplatin is still used in a number of patient populations. The incidence of IV cisplatin–related HSRs is reported to be 5% (Koren et al., 2002). Recent evidence suggests that concurrent pelvic radiation therapy increases a patient’s risk of developing an HSR threefold (4 out of 25, or 16%) (Koren et al., 2002). Researchers theorize that this is due to increased cytokine release from the tumor.

One approach to cisplatin-related HSRs is crossover to carboplatin, although cross-sensitivity has been reported (Zanotti & Markman, 2001). Some case reports in the HSR literature cite an association with intraperitoneal administration of cisplatin (Ozguroologes et al., 1999). With the recent resurgence of intraperitoneal administration of cisplatin (Armstrong et al., 2006), additional information may become available regarding the incidence rate, premedication regimens, and treatment for these specific HSRs.

Oxaliplatin is a third-generation platinum compound that is effective in treating advanced colorectal cancer (Brandi et al., 2002), as well as pancreatic, ovarian, and non-small cell lung cancer (Lenz et al., 2003). The incidence of HSRs to oxaliplatin is reported to be 0.5% to 13% (Brandi et al., 2002). Patients may have an HSR upon first exposure or after a number of cycles (Brandi et al., 2002), which suggests differing underlying mechanisms (anaphylactoid versus anaphylactic). Symptoms generally occur within minutes of starting the infusion (Lenz et al., 2003; Brandi et al., 2002) but have been known to occur after the infusion is complete (Mis et al., 2005). Rechallenge was unsuccessful in one study (Lenz et al., 2003) but successful in another with the addition of dexamethasone, cimetidine, diphenhydramine, acetaminophen, and granisetron (Dold et al., 2002). Some studies suggest that extending the infusion time from 2 hours to 6 hours may reduce the incidence of oxaliplatin-induced HSRs to 1% (Maindrault-Goebel et al., 2001; Giacchetti et al., 2000). A more recent study describes a variety of desensitization protocols involving histamine blockade, serial dilutions of oxaliplatin, and lengthening the infusion time up to 8 hours (Mis et al., 2005).

The incidence of HSRs caused by monoclonal antibodies is directly related to how humanized the medication is (Polovich et al., 2005). The oncology nurse should be fully prepared for a reaction to murine and chimeric (a combination of murine and humanized antibodies) preparations. These reactions can occur on first exposure and on subsequent exposures. Within 30 minutes of the start of the infusion, many patients show symptoms such as rigor, chills, and temperature elevation. Fever and chills are common side effects of monoclonal antibodies that would not be expected in other chemotherapy-related HSRs (Carr & Burke, 2001). Standard protocols for these medications should include premedication, emergency medications (including meperidine to ameliorate rigors), a titration schedule, and monitoring requirements (Polovich et al., 2005).

HSRs to etoposide and teniposide have been reported, although the incidence rate may be as low as 6% (Gobel, 2005). These reactions appear within the first 10 minutes of the infusion and can occur on initial or repeated exposure (Siderov et al., 2002). The underlying mechanism of these HSRs is thought to be related to the excipient used to dissolve the drug into an aqueous solution. Etoposide HSRs are related to the polysorbate 80 (Tween 80) used to dissolve the drug (Weiss, 1997). This assumption is supported by the evidence that there are no reported HSRs to oral etoposide and that patients have been successfully rechallenged with etoposide phosphate (Siderov et al., 2002). Teniposide is solubilized in the excipient Cremophor EL; as with the taxanes (Gobel, 2005), this specific excipient is thought to cause the HSRs seen with this drug. Although these drugs have a low incidence of HSRs, nurses need to remain vigilant in monitoring patients for HSRs throughout the duration of treatment cycles.

Asparaginase HSRs occur in 10% to 25% of patients (Carr & Burke, 2001). They can occur on first administration, although they are more common with repeated administrations or when the drug is reintroduced after a break in the treatment plan of 1 week or longer (Wilkes & Barton-Burke, 2006). Intravenous administration increases the occurrence and severity of HSRs compared to intramuscular administration (Polovich et al., 2005; Zanotti & Markman, 2001). Also, patients have more HSRs with intermittent dosing than with continuous dosing (Zanotti & Markman, 2001). An HSR to asparaginase can occur immediately after administration or within 1 hour of intravenous or intramuscular administration. The clinical presentation can range from a mild rash to severe and potentially life-threatening complications. Skin testing is recommended before the first dose and if a break of 1 week or longer has occurred since the last exposure (Spratto & Woods, 2005). Because an asparaginase HSR likely is related to the use of a live bacterium (Escherichia coli) in the preparation (Skidmore-Roth, 2006; Zanotti & Markman, 2001), when an HSR occurs, the patient potentially can be treated with an alternative preparation of the drug, such as Erwinia carotovora L-asparaginase or polyethylene glycol–modified (PEG) asparaginase. Emergency medications should be readily available with these other preparations as well.