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Journal of

Oncology
Pharmacy
Research Article Practice
J Oncol Pharm Practice
17(3) 155–159

Single premedication dose of ! The Author(s) 2010
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dexamethasone 20 mg IV before DOI: 10.1177/1078155210367950
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docetaxel administration

Jyoti D Chouhan
Department of Pharmacy, Scott & White Memorial Hospital and Clinic, Temple, TX, USA;
The University of Texas at Austin College of Pharmacy, Austin, TX, USA

Jon D Herrington
Department of Pharmacy, Scott & White Memorial Hospital and Clinic, Temple, TX, USA;
The University of Texas at Austin College of Pharmacy, Austin, TX, USA; Texas A&M Health
Science Center College of Medicine, Temple, TX, USA

Abstract
Background: The administration of docetaxel requires the use of dexamethasone for the prevention of hypersensitivity
reactions (HSRs) and fluid retention reactions (FRRs). The manufacturer recommends dexamethasone for 3 days starting
the day before docetaxel. This regimen has the potential for nonadherence so the utility of a single dexamethasone dose
would be welcomed.
Objective: To ascertain the incidence of HSRs and FRRs after receiving a single dose of intravenous dexamethasone
before docetaxel administration.
Design: Retrospective chart review.
Setting: Data set from an oncology clinic affiliated with a large, tertiary, academic, teaching hospital.
Patients: Ninety patients (median age 59 years, range 40–92 years) with cancer (primarily breast cancer, nonsmall cell
lung cancer and head/neck cancer) who received docetaxel.
Measurements and Results: Patients with heart failure, renal failure, chronic edema, current steroid use and/or
prostate cancer were excluded from the study. Seven patients (7.8%) experienced a HSR requiring a treatment inter-
vention (fluid bolus, oxygen, steroid, and/or diphenhydramine). Eleven patients (12.2%) had documented fluid retention.
The mean docetaxel dose at the onset of fluid retention was 247.2  134.5 mg/m2.
Limitations: This single center evaluation with a small sample size had the potential for incomplete collection of the
adverse events from the medical records due its retrospective nature.
Conclusion: Hypersensitivity reactions and FRRs occurred in 7.8% and 12.2% of patients, respectively. This is lower
than the rates reported by the manufacturer with the oral premedication regimen.

Keywords
Docetaxel, corticosteroid, dexamethasone, premedication, hypersensitivity, fluid retention, edema, effusion

warnings exist for HSRs and FRRs. From an adher-
Introduction ence standpoint, either or both of these reactions have
Docetaxel, a microtubule inhibitor, is approved by the the potential to interfere with its administration.
Food and Drug Administration for use in multiple
malignancies including breast, lung, prostate, gastric
Corresponding author:
and head and neck cancers.1 Hypersensitivity reactions Jon D. Herrington, Department of Pharmacy, Scott & White Memorial
(HSRs) and fluid retention reactions (FRRs) are major Hospital, 2401 South 31st Street, Temple, Texas 76508, USA
adverse events of this medication. Currently, black box Email: jherrington@swmail.sw.org

8%) experienced a HSR requiring a tion. If patients have trouble picking up their (three patients).5 were excluded from this evaluation if they had conges. Three of these seven patients severe HSRs and FRRs is much lower (2. A single dose of dexamethasone episodes within the first two cycles. Characteristics N ¼ 90 spective chart review. hypotension. sweating. oxygen. Chest pain and back pain were also prescription or forget to start their 3-day regimen the reported in two patients each. Despite premedica. and edema. Texas.9 rent corticosteroid use. All seven patients developed HSR over the 3-day period.3 menting the type of HSR and/or FRR along with any Other 5. respectively).median (range). N ¼ 8 30 (20–35) HSRs included rigor. 6. flushing (four patients). and anaphylaxis that required an intervention Cyclophosphamide 35. steroid.median (range). the manufac- turer advocates a 3-day premedication strategy of A total of 90 patients were included in the analysis. academic.5%. bronch. Concurrent chemotherapy agent(s) (N%) ospasm.2% and (42. not receive any additional premedication before doce- blems or any patient dissatisfaction from taking taxel administration for their subsequent cycles and multi-day dexamethasone. steroid. dyspnea. flush. urticaria. Trastuzumab 14. concur. chronic edema. Additionally. The reactions consisted of dyspnea (six adverse events relating to a large total dose of dexa. One patient received lor- native premedication regimen utilizes a single intrave.9%) had a repeat reaction when rechallenged. All patients must have received their first dose of docetaxel no earlier than January 2006. an alter. Every 3 weeks . Carboplatin 28. patients may rence of chest pain accompanied by an irregular pulse be susceptible to corticosteroid-related adverse events with the third cycle. This was an IRB-approved study Gender that was conducted using the records of outpatient Male 15 oncology patients at Scott and White Memorial Female 75 Hospital and Clinics in Temple. N ¼ 82 75 (60–100) ing. and 64. Scott and Age (years) White Hospital is a >600 bed. completed all planned cycles. At our institution.4 mens that include daily prednisone. Seven patients (7.77 (1. azepam orally and diphenhydramine intravenously in nous (IV) dose of dexamethasone 20 mg administered addition to the standard premedications at the fourth on the treatment day before docetaxel infusion. Four patients did before docetaxel would alleviate the nonadherence pro. oxygen. HSRs and FRRs have continued to occur (15.5 subsequent interventions. angioedema. Secondary objectives include docu- Doxorubicin 13.4 ascites. To prevent or delay these events. Patients Breast 65. One patient who com- day before treatment.1%.1 Currently. Other 4. corticosteroid pre- Results medication is recommended.1 However. teach- Median (Range) 59 (40–92) ing hospital that primarily serves patients in the Central Cancer Diagnosis (N%) Texas region. and/or diphenhydramine). respectively). starting the day before treatment. discussed in this report. Nonsmall cell lung cancer 20 tive heart failure. and hypotension methasone. Patients did not receive docetaxel desensitization prior oid premedication include patient adherence and to rechallenge.5 (fluid bolus.34–2.1 cancer since these patients may have chemotherapy regi. the incidence of and/or diphenhydramine). hives. subsequent delays in initiating plained of chest pain with the first cycle had a recur- chemotherapy can occur.67) the incidence of HSRs and FRRs as described in the Initial dose (mg/m2) and frequency of docetaxel electronic medical record. patients). Demographics The efficacy of a single. Two patients Methods Table 1.2% treatment intervention (fluid bolus. Head/neck 8. and/or diagnosis of prostate Gastric 1. renal failure. the cumulative .156 J Oncol Pharm Practice 17(3) The mechanisms underlying each reaction have not dose of docetaxel at the time of fluid retention was been fully elucidated but theories do exist and will be calculated.9 Search terms utilized for FRRs included effusion. Additionally. BSA (m2) The primary objective of the study was to evaluate Median (range) 1. dexamethasone 8 mg orally (PO) twice daily (BID) Please see Table 1 for demographic information. Search terms utilized for Every week . fever. Other issues surrounding oral ster. cycle and finished all cycles as planned. tertiary. IV dose of dexamethasone 20 mg before docetaxel administration was evaluated via retro.

Twenty-two patients had a diagno. most of their sis of nonsmall cell lung cancer and one patient had effects are delayed and may take several hours to advanced head and neck cancer. three were given diuretics and one had treatment with the use of technetium-labeled albumin demonstrated docetaxel discontinued. This includes their use in allergic reac- nificant decreases in the colloid osmotic pressure of tions and is a reason why patients who have severe aller- plasma (COPpl) and colloid osmotic pressure of the gic reactions (e. is logical based on the delayed onset of activity ted fluid retention. site which leads to retention of proteins and subse- quently leads to water retention between the second and fourth cycles.3 In humans. bition of cyclooxygenase-2 and phospholipase A2.Chouhan and Herrington 157 had treatment discontinued after the HSR occurred. HSRs with a single. However.g. As for documen. they demonstrated fluid retention was 247. premedica. the COPint did stabilize or the day before treatment. Seven of 12 patients experienced edema at collected. is unknown how corticosteroids delay or prevent tion in these patients. A 5-day.4 dexamethasone was responsible for earlier time to FRR With regard to FRRs. Four congestion. it would seem that there was not an increase in 500 mg/m2 and one patient required treatment with fur. inhi- Transcapillary forces were measured before the start bition of IgE-dependent histamine and leukotriene C4 of treatment and after cumulative docetaxel doses of release. anaphylaxis) require immediate interstitial fluid (COPint) at a cumulative dose of therapy with epinephrine. patient experienced a pleural effusion after nine courses phosphamide to doxorubicin and cyclophosphamide. patients were to begin their in the expression of pro-inflammatory cytokines by inhi- corticosteroid the day before each course.. the patients had documentation or treatment of FRR nologic in nature. confirmed early theories of drug-induced capillary leak ted fluid retention.6 At this point. This scenario is completed by the fifth cycle peripheral edema while pulmonary edema and a pleural where the lymphatic system fails to prevent the effusion were noted in one additional patient. There is evidence to suggest that polysorbate 80. median docetaxel dose was almost 100 mg/m2 with the the vehicle in which docetaxel is solubilized. IV dose prior to docetaxel osemide daily for 3 weeks. involved in this suppression. it in 1998 that tried to elucidate the cause of fluid reten. chemoattractive factors.7 Multiple mechanisms are tion regimen of dexamethasone 8 mg PO BID was uti.4%. The lished. The authors concluded that their results Eleven patients (12. The patient would patients receiving docetaxel have not been well estab. the HSR is thought to post docetaxel which is lower than the manufacturer be non-IgE mediated since most reactions occur within package insert of 64. The authors noted sig. and water mixtures. None of the patients administration. Only 12.2  134.5 mg/m2. developed signs of drug-induced ascites and only one their regimen was switched from docetaxel and cyclo. The mean docetaxel dose at the the toxicity is primarily at the capillary endothelium onset of fluid retention was 247. three patients had Grade 1 edema at of corticosteroids. Regarding HSRs. Starting the dexamethasone 200 mg/m2. Because of this. nonionic surfactant that is used to emulsify oil tion was not accompanied by episodes of dehydration. Allergy-mediated reactions have oliguria or hypotension and was slowly reversible upon been demonstrated in animals using both oxidized discontinuation of docetaxel. is the cause median cumulative dose to FRR onset was 301 mg/m2 for docetaxel-induced HSR.. there is considerable Discussion variability. 95–710 mg/m2). (range.4%) received some type of intervention. begin exhibiting signs and symptoms of edema. dexamethasone and other advanced or metastatic cancer received docetaxel corticosteroids have long been known to have potent 100 mg/m2 every 3 weeks over 1 h. Semb and colleagues published a study venting these adverse events? In terms of FRR. based on the data that was baseline. were most likely linked to the challenges of discerning oped peripheral edema and nonmalignant effusions. the edema data from the medical records and the small This phenomenon5 was observed in >50% of patients sample size. it was noticed that some or if it was due to the study design. Docetaxel-related fluid reten- philic.2 Polysorbate 80 is a hydro.2% of that polysorbate 80-mediated HSR may be nonimmu.2  134.5 Twenty-four patients with the edema. of docetaxel. the mean docetaxel dose to onset of been challenged by Coors et al. patients (36. anti-inflammatory effects. become apparent. However. These differences patients receiving docetaxel in early clinical trials devel.5 mg/m2. Additionally.1 It is unknown if this single the first two doses.2%) had some type of documen. this idea has In our study. ufacturer. who had received a cumulative docetaxel dose of Why do corticosteroids seem to have an effect in pre- 400 mg/m2. 10 of these 11 patients (91%) had syndrome. and nonoxidized products. and a decrease in the release of vasoactive and 200 and 500 mg/m2. . but capillary hyperpermeability leading to The mechanisms underlying both HSRs and FRRs in lymphatic failure could appear. However. These include a reduction lized. In a study in patients not receiving corticosteroids. as is recommended by the man- increase slightly with further courses.

Magnusson K. Taxotere (docetaxel) package insert. 8. cacy of docetaxel given every 3 weeks versus weekly 7. not reported 1. Ann Allergy 2003 and February 2006. 64% and 62% (no premedica- tion.9%) with two patients having edema with 5. methylprednisolone 40 mg PO or dexamethasone 8 mg PO BID for 3 days or dexamethasone 8 mg 8 mg PO TID for 2 days starting the evening before PO BID for 3 days plus the experimental vascular pro. 5-day regimen. NJ: 2007. The authors con. With this data. exposure. and Karlberg AT. The incidence of severe fluid retention was FRRs occurred in 7. 399 mg/m2 and 399 mg/m2 this evaluation. and Oian P. 102: 179–187. 3 day-regimen.8 Three hundred and peripheral edema in the weekly docetaxel group was sixty-one patients with either metastatic breast cancer or 2. alternative corticosteroid premedication regimens. 6. was 4. While multiple studies have been conducted using 3. all were asymptomatic and required patients who receive docetaxel treatment. Béhar A. the morning of infusion. No information on HSRs was reported. Sanofi-Aventis. References cation. J Clin Oncol no treatment intervention.1587–1612. dexamethasone (8–20 mg). 705 mg/m2. analysis showed that there was a reported by the manufacturer with the oral premedica- nonsignificant difference between the 5-day and 3-day tion regimen. New York.11 The incidence of HSRs tectant.3% in the every three weeks docetaxel nonsmall cell lung cancer were randomized to one of group. Diagnosis and 64 patients received single dose dexamethasone prior to management of hypersensitivity reactions related to every 3-week docetaxel administration between March common cancer chemotherapy agents. The incidence of fluid and 1. Ann Allergy Asthma Immunol only one has published data using a single. In the four premedication regimens: no premedication. and Mahler V. Roche H.3%. All patients received docetaxel were 0% for those receiving docetaxel every 3 weeks 100 mg/m2 IV every 3 weeks. receiving corticosteroid comedication. 6%. Lee C.2% of patients. the evening of the infusion and then dication regimen comes from data published in abstract BID the day following the infusion. The incidence of HSRs 1998.8% and 12. This is lower than the rates respectively). 4. Lastly. Contact Dermatitis 1997. Bridgewater. day. 3-day regimen plus diosmine. Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. used premedication strategies that differed from the adrenalcortical steroids and their synthetic analogs. 95: 593–599. before infusion. dexamethasone PO. Lazo JS. Semb KA.6% for those receiving docetaxel weekly. p. Riva a. et al. respec- 22%. Bergh M. retrospective nature of dose 322 mg/m2. New pleural effusions occurred in three syndrome appears to explain fluid retention in cancer patients (4. cluded that the 3-day corticosteroid regimen was as 2. Maurel A. Schimmer BP. Pujade-Lauraine E. Adrenocorticotropic hormone. the onset of moderate or severe FRR occurred at a cumulative dose of 490 mg/m2. effective as the 5-day regimen and that the use of dios. patients In: Brunton LL. et al. Aamdal S. retention was 82%. Giano M. Coors EA. the authors recommended 6. Nilsson JL.4% and 7. 37: 9–18. 11th ed. 5-day regimen. and 819 mg/m2 (no premedi. but not There are two additional studies comparing the effi. NY: McGraw-Hill. patients (10.7%). 3-day regimen. dexamethasone dose. Again. manufacturer recommendations. before treatment and on the evening of the treatment 2006. Efficacy and safety of dexamethasone 8 mg was administered PO the night different corticosteroid (C) premedications (P) in breast before infusion. patients could receive prednisolone 50 mg methasone 8 mg PO BID for 5 days. docetaxel administration. The that single dose dexamethasone be used to avoid hyper. The onset of FRR occurred at a cumulative ences are a small sample size. The incidence of form only by Riva and colleagues. regimen plus diosmine.158 J Oncol Pharm Practice 17(3) The manufacturer recommended oral. 396 mg/m2. pathophysiological mechanism of fluid retention in sensitivity reactions. Seybold H. Merk HF. 3-day experiencing a HSR or FRR. with the administration of a single 20 mg IV imen. Fumoleau P. and Klaustermeyer WB.9 In this retrospective review. Paker KL.5% and 5% (no premedication. 3-day regimen plus Conclusion diosmine. one hour Therapeutics. In one study. Analysis showed that there was a nonsignificant difference between the 5-day and 3-day Hypersensitivity reactions requiring interventions and regimens. diosmine. Contact allergenic activity of Tween 80 before and after air mine did not add a significant benefit. 52%. 5-day regimen. for 3-day regimen plus diosmine). Edema developed in seven Asthma Immunol 2009.10 For patients receiving docetaxel three weeks. and the inability to capture all patients (no premedication. Br J Clin Pharmacol 1997. 43: 653–658. IV dose of 2005. tively. Capillary protein leak weight gain. respectively). respectively). 16: 3426–3432. dexa. second study. one hour cancer (BC) patients (pts) treated with Taxotere (T) . and 3-day regimen. advanced cancer patients treated with docetaxel. steroid preme. 3-day regimen. Reasons that may explain these differ- regimens. and Paker KL (eds) receiving weekly docetaxel were given dexamethasone Goodman and Gilman’s The Pharmacological Basis of 8 mg PO to take the morning of treatment. 5-day reg.

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