Nanoparticle albumin-bound paclitaxel in a patient with locally advanced breast cancer and taxane-induced skin toxicity: a case report.

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by  Cirauqui, Beatriz Cirauqui

Cirauquietal.JournalofMedicalCaseReports2014,8:6
JOURNAL OF MEDICAL
http://www.jmedicalcasereports.com/content/8/1/6
CASE REPORTS
CASE REPORT Open Access
Nanoparticle albumin-bound paclitaxel in a
patient with locally advanced breast cancer and
taxane-induced skin toxicity: a case report
Beatriz Cirauqui Cirauqui1,5*, Vanesa Quiroga García1, Clara Lezcano Rubio2, Maria Iciar Pascual Miguel3,
Laia Capdevila Riera1, Nuria Pardo Aranda1, Sara Vizcaya Martín3, Antonio Mariscal Martínez3,
Clara Rodríguez Caruncho4 and Mireia Margelí Vila1
Abstract
Introduction: Taxanes have demonstrated effectiveness inthe treatment of breast cancer, themost common type
ofcancer inwomen. The toxicityprofile of taxanes (including skin toxicities)induces dose adjustment, delay, or
discontinuation, which prevents a sufficient dose intensity to achieve a response. Nanoparticle albumin-bound
paclitaxel, a solvent-free form of paclitaxel, prevents toxicities and reduces the pharmacokinetic interferences
between paclitaxel and other drugs.
Case presentation: We describe the case of a 55-year-old Caucasian woman with locally advancedbreast cancer
treatedwithneoadjuvanttherapywhodeveloped secondaryskintoxicityduetodelayedhypersensitivitytotaxanes.
She received Adriamycin® (doxorubicin), cyclophosphamide and docetaxel and developed toxicitythat promoted
treatment delay and a switch to weekly paclitaxel.After thethird and fourth weeks of treatment, paclitaxel toxicities
also induced treatment delay and paclitaxel was switched to nanoparticle albumin-bound paclitaxel.She completed
thefive planned nanoparticle albumin-bound paclitaxel cycles with acceptable tolerability (including persistent
grade 2 neuropathy) and without dose delay or adjustments.Clinical response was achieved althoughpathological
response was not good.
Conclusions: Nanoparticle albumin-bound paclitaxeltreatment is a good option for patients with breast cancer
withtaxanes-related skin toxicity. Thisdrugallows thetreatmentto be completed with acceptabletolerance inour
case.
Keywords: Breast cancer, Nab-paclitaxel, Taxane-induced toxicity
Introduction limit the clinical effectiveness of taxanes, induce a toxic
Breast cancer is the most common type of cancer diag- response [2] and increase the adverse effects experienced
nosed in women [1]. Breast cancer is a heterogeneous dis- by patients with breast cancer, such as myelosuppression,
easeregardinggeneexpression,morphology,clinicalcourse neurotoxicity, arthralgia and/or myalgia, and hypersensi-
andtreatmentresponse[2]. tivity reactions. It has been shown that Cremophor® used
Taxanes have shown significant activity in early and ad- as a solvent in paclitaxel is associated with major side
vanced breast cancer [3]. Due to the hydrophobic pro- effects including neutropenia, hypersensitivity reactions,
perties of taxanes, solvents are required for intravenous and neuropathy due to axonal degeneration. Tween 80®,
administration (Tween 80® and Cremophor®) [4]. Solvents the solvent used indocetaxel, hasbeenshown to partially
contribute to fluid retention by altering membrane fluid-
*Correspondence:[email protected] ity. These toxicities often require dose delay, adjustment
1DepartmentofMedicalOncology,CatalonianInstituteofOncology,
orevendiscontinuationoftaxanes.
GermansTriasiPujolHospital,Badalona,Spain
5CatalonianInstituteofOncology.GermansTriasIPujolHospital,Carreterade Nanoparticle albumin-boundpaclitaxel(nab-paclitaxel;
Canyets/n.08916,Badalona,Spain Abraxane®) is a solvent-free form of paclitaxel, which
Fulllistofauthorinformationisavailableattheendofthearticle
©2014Cirauquietal.;licenseeBioMedCentralLtd.ThisisanopenaccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.
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eliminates the risk of toxic solvents. Substitution of receptors (PR) and without overexpression of c-erbB-2
solvent-basedpaclitaxelpreventstoxicitiessuchas hyper- (score1).
sensitivityreactionsandlong-standingneuropathy,reduces A needle biopsy from two of the enlarged axillary
the pharmacokinetic interferences between paclitaxel and lymph nodes and the enlarged intramammary lymph
other drugs, and decreases the complexity and inconve- node in her breast tail was consistent with metastasis of
niencesofpaclitaxeldosing[5]. carcinoma.
Weherediscussacaseofapatientwhoreceivedtaxanes The staging evaluation showed no evidence of distant
and developed skin toxicity; the taxanes were replaced by spread.
nab-paclitaxel, which allowed her to complete her neoad- Neoadjuvant chemotherapy was administered based
juvantchemotherapyschedule. on the high burden of axillary disease and the risk of
microscopic dissemination, and on the hormone status
Case presentation (PR negative) that suggested a luminal B tumor type
A 55-year-old Caucasian postmenopausal woman with a which is likely to benefit from chemotherapy and evi-
history of penicillin allergy, dyslipidemia with hypolipid- dence of response after neoadjuvant chemotherapy in
emic diet treatment and no substance abuse, was re- lobular-type tumor [6]. The patient received four cycles
ferred to our Breast Pathology Unit when a left axillary of Adriamycin® (doxorubicin, 60mg/m2) and cyclophos-
lymph nodewasnoted onpalpation. phamide(600mg/m2)every3weeks,achievingpartialre-
The examination revealed a hard fixed matted lymph sponse on physical examination. Docetaxel (100mg/m2)
node mass of 5×3.5cm on her left axilla, and a 1×1cm was started subsequently, with cycles every 21 days for 4
lump in her left breast axillary tail. The mammography planned courses.
showed a 20 to 24mm, dense, well-defined left breast Aftercycle1,thepatientdevelopedgrade3skintoxicity
nodule (upper external quadrant), and dense well- (with a predominance of erythrodysesthesia on the soles
defined nodules in the left axillary space, the largest one of her feet and on the palms and dorsa of her hands),
measuring 4 to 5cm. In addition, an ultrasound scan re- grade 3 arthralgia and myalgia, and grade 2 asthenia
vealed a 2cm well-defined, hypo to anechoic nodule in (Figure 1). This significant toxicity promoted a 1-week
the upper outer quadrant of her left breast tail. The left chemotherapy delay. Symptoms were managed with
axillary nodules were abnormally enlarged lymph nodes, anti-inflammatory drugs and oral and topical steroids;
all of them hypoechoic with cortical thickening. Eccen- signsandsymptomsimprovedtograde1.
trichilum wasabsentinsome ofthenodes. Subsequently,theseverityoftheskintoxicityassociated
The examination was completed with a magnetic res- with docetaxel involved treatment-switching to paclitaxel
onance imaging (MRI) of her breasts, which detected a 80mg/m2 weekly. After the first week of this treatment
lesion at the junction of the outer quadrants, close to neither new toxicities occurred nor pre-existing toxicities
the retroareolar region of her left breast. The lesion had increased. After the second week, the patient developed
undefined margins and two adjacent areas of focal up- paclitaxel toxicities that included grade 1 diarrhea and
take measuring 2×1.7×2cm, and multiple enlarged left grade1peripheralneuropathy.
axillary lymph nodes extending from her breast tail to Tolerability of treatment decreased after the third
levels IandII. week of paclitaxel, and toxicities included grade 2 asthe-
A biopsy of the retroareolar area was consistent with nia, grade 2 peripheral neuropathy, grade 2 diarrhea,
infiltratinglobularcarcinoma,100%ofthetumorcellswere and grade 2 skin and nail toxicity. These toxicities pro-
positive for estrogen receptor, negative for progesterone moted chemotherapy delay and she was treated with
Figure1Grade3skintoxicitysecondarytodocetaxel.
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gabapentin, loperamide, and oral and topical steroids. notified. Hypersensitivity reactions, both acute (charac-
The fourth dose of paclitaxel was administered 1 week terized by skin rash) and delayed (in the form of blisters,
later; the patient developed the same symptoms and the diffuse pustular rash with exfoliation, pruritic maculo-
treatmentrequiredafurtherdelay. papular rash, scleroderma-like lesions, or hand-foot syn-
As aconsequenceof hersymptomsandtheimportance drome) havebeen reported [7-10].
ofchemotherapydoseintensityintheneoadjuvantsetting, With docetaxel treatment, most patients develop some
paclitaxelwasswitchedtonab-paclitaxel100mg/m2weekly. type of skin toxicity, which is usually mild and self-
Standard paclitaxel would have required a dose reduction limited. These reactions include hypersensitivity, edema,
orfurtherdelaysintreatment(Figure2). erythrodysesthesia, erythema multiforme, nail changes,
Tolerability was acceptable with resolution of diarrhea, photosensitivity, scleroderma, and subacute cutaneous
improvements in skin toxicity and asthenia to grade 1, lupuserythematosus [10-12].
and persistence of grade 2 neuropathy. She completed These skin toxicities secondary to taxanes seem to be
the five planned weeks of treatment without delays or immune-mediated. Both acute and chronic hypersensi-
doseadjustment. tivity reactions may be secondary to the cytotoxic agent
Post-treatment breast imaging with mammography, itself or to any of its additives. Cremophor® has been re-
ultrasound,andposteriorMRI,showedcompleteresponse portedtobeinvolvednotonlyinhypersensitivityreactions
oftheretroareolarlesionandpartialresponseoftheen- butalsoinchangesinthepharmacokineticsofpaclitaxel.
larged intramammary lymph node and axillary lymph Due to thetoxic effectsreported, the dose ofpaclitaxel
nodes. and docetaxel that can be administered is limited. In
As a result of this good response, tumorectomy with chemotherapy, dose intensity is a well-known major de-
axillary lymph node removal were performed. Histology termining factor in the prognosis of patients with breast
showed infiltrating lobular carcinoma measuring 1.5cm cancer, and even a linear relationship between both was
with lower anterior and posterior margins involved, and identified [13]. Bonadonna et al. reported that the re-
metastasesfrominfiltratinglobularcarcinomawithpleo- sponse rate to primary chemotherapy is probably more
morphic areas and signet ring cells in 20/20 isolated related to dose intensity than to the chemotherapy regi-
lymph nodes, the largest one measuring 2cm in longest men itself [14]. The importance of achieving complete
diameter. response is also well established in the neoadjuvant set-
Asmarginswereinvolved,amastectomywasperformed ting for long-term prognosis, with lower relapse rate and
atasecondstageandnoresidualmalignancywasfound. increasedoverallsurvival[15].
Nab-paclitaxel has shown good clinical results in first-
Discussion and further-linetherapy of patients withmetastaticbreast
The use of taxanes has been associated with a number cancer (MBC) and it has also demonstrated considerable
of skin toxicities. With paclitaxel, administration site re- activity in taxane-pretreated patients with MBC. Because
actions are generally rare and mild, ranging from ery- oftheexcellenttolerabilityofnab-paclitaxelinhypersensi-
thema or phlebitis to depigmentation. Paclitaxel is tivity reactions to docetaxel and paclitaxel, we decided to
considered irritating rather than vesicant, and lesions administer weekly nab-paclitaxel in a patient with locally
from extravasation are usually mild; however, edema, advanced breast cancer with skin toxicity secondary to de-
cellulitis,and even necrosis have also been reported. An- layedhypersensitivitytotaxanes.Noskintoxicityoccurred,
other type of skin toxicity is the “recall effect”, both in whichallowedustocompleteneoadjuvanttreatment.
previously irradiated areas and in extravasation sites. In2009,Gradisharetal.performedarandomizedPhase
Some isolated cases ofnail bed ulceration havealso been IIstudy with302patientswithpreviouslyuntreatedMBC
Figure2Improvementofskintoxicityduringtreatmentwithnanoparticlealbumin-boundpaclitaxel.
Cirauquietal.JournalofMedicalCaseReports2014,8:6 Page4of4
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human epidermal growth factor receptor-2 negative pa- Received:19June2013Accepted:19September2013
tients who either received nab-paclitaxel 300mg/m2 every Published:3January2014
3weeks,100mg/m2weeklyor150mg/m2weekly,ordoce-
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Authors’contributions doi:10.1186/1752-1947-8-6
Citethisarticleas:Cirauquietal.:Nanoparticlealbumin-boundpacli-
BCCfollowedupandmanagedthepatientanddraftedthemanuscript.VQG
taxelinapatientwithlocallyadvancedbreastcancerandtaxane-
draftedthemanuscript.CLRmanagedandcontrolleddrugs.MIPM inducedskintoxicity:acasereport.JournalofMedicalCaseReports
performedsurgery.LCRandNPAmanagedthepatient.SVMandAMM 20148:6.
diagnosedthepatient.CRCtreatedandfolloweduptheskintoxicity.MMV
draftedthemanuscript.Allauthorsreadandapprovedthefinalmanuscript.
Authordetails
1DepartmentofMedicalOncology,CatalonianInstituteofOncology,
GermansTriasiPujolHospital,Badalona,Spain.2DepartmentofPharmacy,
CatalonianInstituteofOncology,GermansTriasiPujolHospital,Badalona,
Spain.3BreastPathologyUnit,GermansTriasiPujolHospital,Badalona,Spain.
4DepartmentofDermatology,GermansTriasiPujolHospital,Badalona,Spain.
5CatalonianInstituteofOncology.GermansTriasIPujolHospital,Carreterade
Canyets/n.08916,Badalona,Spain.