Breast Cancer
`
`Taxane ChemotherapyAdvances
`
`in Treatment
`
`for Breast Cane
`
`Debra K Frye RN BSN OCN CCRP
`
`a report by
`
`Research Nurse Manager Department of Breast Medical Oncology
`University of Texas MD Anderson Cancer Center
`DO 10179250HR2006000140
`
`chance
`
`invasive
`
`breast
`
`cancer
`
`The
`of developing
`sometime in a womens life is about one in eight 13 of
`women In fact breast cancer is the most common cancer
`among women except
`for nonmelanoma skin cancer
`and women living in North America have the highest
`in the world In 2006 about 212920 new
`of breast cancer
`cases of invasive breast cancer will be diagnosed among
`women in the US and an estimated 1720 cases of breast
`cancer will be diagnosed in men Breast cancer
`is the
`second leading cause of cancer death in women exceeded
`In 2006 40970 women and 460
`only by lung cancer
`men will die from breast cancer Fortunately death rates
`been declining since 1990
`from breast
`cancer
`have
`
`rate
`
`and increased
`therapy duration of
`survival
`response
`Unfortunately the majority of these agents failed to show
`benefit andor produced
`unacceptable toxicities
`
`initially
`
`extracted
`
`The taxanes are a class of anticancer agents that bind to
`and stabilize microtubules causing cellcycle arrest and
`apoptosis cell death Paditaxel
`from
`the bark of the Pacific yew Taxus brevyolia was identified
`Institute NCI pro
`in 1971 as part of a National Cancer
`gram that screened medicinal plants for potential activity
`in 1986 using a precursor
`Docetaxel
`was
`extracted from the needles of the European yew T baccata
`in its mechanism of action
`and is similar to paclitaxel
`
`synthesized
`
`believed to be the result of early detection and improved
`treatment Two studies that explored survival of patients
`
`Results from clinical
`
`trials designed in the late 1980s have
`
`with recurrent breast cancer over
`
`taxanes
`
`the most
`
`active
`
`Debra K Frye RN BSN OCN CCRP
`
`is Research Nurse Manager
`
`in the
`
`Department
`
`of Breast Medical
`
`Oncology
`
`at
`
`the University
`
`of Texas
`
`MD Anderson
`
`Cancer Center
`
`Houston
`
`Texas
`
`She
`
`is
`
`an
`
`experienced
`
`breast
`
`cancer
`
`nurse
`
`clinician
`
`and researcher
`
`as well
`
`as
`
`author
`
`and educator
`
`Ms
`
`Frye
`
`has
`
`coauthored
`
`over
`
`SO papers
`
`six
`
`the past two to three
`
`book
`
`chapters
`
`and more
`
`than 75
`
`decades
`
`have suggested that
`
`the improvement
`
`in recent
`
`years is associated with introduction of taxane therapy
`
`abstracts
`
`on
`
`novel
`
`therapies
`
`for
`
`breast
`
`cancer and associated
`
`nursing
`
`and other
`
`clinical
`
`issues as
`
`well
`
`as
`
`developing
`
`educational
`
`materials
`
`for
`
`patients
`
`with
`
`this
`
`malignancy
`
`She
`
`has
`
`spent
`
`her
`
`entire
`
`30 year
`
`career
`
`in oncology
`
`nursing
`
`at
`
`the
`
`University
`
`of Texas
`
`shown that
`
`chemotherapy
`
`agents
`
`are among
`used
`in the management of
`metastatic breast cancer Positive trials in the adjuvant and
`setting have more recently
`
`neoadjuvant
`changed practice
`standards These agents may be considered
`powerful group of compounds
`developed in the 1990s
`
`the most
`
`In metastatic breast cancer cytotoxic chemotherapy
`is the
`treatment of choice for patients with hormone receptor
`negative tumors refractory to hormone therapy or with
`rapidly progressive disease regardless of hormone status
`on
`The choice of optimum chemotherapy
`factors such as
`the type of previous
`of the disease the sites
`
`several
`
`chemotherapy the aggressiveness
`
`is dependent
`
`adjuvant
`
`MD Anderson Cancer Center
`
`in
`
`Houston
`
`Texas where
`
`she
`
`began as
`
`an
`
`inpatient
`
`staff nurse
`
`in general
`
`oncology
`
`and
`
`progressed
`
`to out
`
`patient
`
`clinic
`
`nurse clinic
`
`nurse
`
`manager
`
`senior
`
`research
`
`nurse and
`
`research
`
`nurse supervisor
`
`all
`
`in
`
`of metastases the patients age and the toxicity profile
`
`the Department
`
`of Breast
`
`Initial
`
`chemotherapy
`
`choices for the treatment of newly
`
`Medical Oncology
`
`diagnosed and metastatic breast cancer have dramatically
`
`the
`
`Paditaxel Taxolk
`tolerated Most of
`
`and
`
`docetaxel
`
`generally well
`
`TaxotereR are
`the common side
`
`effects are
`
`easily
`
`reversible
`
`and
`
`largely preventable
`
`Hypersensitivity is infrequent but potentially serious It
`
`occurs
`
`rarely if appropriate premedication such as
`an H2
`andor
`dexamethasone
`
`diphenhydramine
`
`occurs
`in about
`antagonist
`is given Hypersensitivity
`10 of patients treated with paclitaxel due to cremaphor
`in the paclitaxel preparation with anaphylaxis and severe
`
`in 24 characterized by
`
`changed
`
`over
`
`past
`
`four decades
`
`evolving
`
`from
`
`marginally
`
`effective
`
`nonanthracycline
`
`single agent
`
`hypersensitivity
`
`reactions
`
`therapies to nonanthracydine
`
`such
`
`as
`
`containing combinations
`and 5
`cyclophosphamide
`fluorouracil CMF and CMF plus
`and
`prednisone CMFVP In the latter 1970s and throughout
`the 1980s the use of anthracydinecontaining
`regimens
`
`methotrexate
`
`vincristine
`
`dyspnea hypotension
`
`angioedema and generalized
`
`urticaria Those with less severe reactions
`
`have been
`
`given
`
`increased
`
`corticosteroid prophylaxis
`
`and have
`
`rechallenged with slower infusions of
`been successfully
`drug Significantly less hypersensitivity is observed when
`
`such
`
`as
`
`5fluorouracil
`
`adriamycin
`
`and
`
`cyclo
`
`paclitaxel
`
`is given weekly
`
`phosphomide FAG cydophosphamide
`doxorubicin
`and 5fluorouracil CAF and adriamycin and cydo
`phosphomide AC resulted in higher response rates and
`time to progression but
`disease During the 1980s many
`agents were explored in clinical
`
`advantage in metastatic
`
`investigational
`
`trials
`
`longer
`
`failed to show survival
`
`with hope of improvement
`
`in the patients response to
`
`Patients receiving either paclitaxel or docetaxel are at risk
`
`for severe neutropenia neutropenic
`Anemia occurs frequently but thrombocytopenia is rare
`
`fever and infections
`
`Fatigue malaise and generalized weakness may occur
`with either taxane
`
`40
`
`US ONCOLOGICAL DISEASE
`
`2006
`
`Abraxis EX2002
`Actavis LLC v Abraxis Bioscience LLC
`1PR201701101 1PR201701103 1PR201701104
`
`

`

`Taxane ChemotherapyAdvances
`
`in Treatment
`
`for Breast Cancer
`
`occurs
`
`and
`
`is
`
`in most patients
`Complete alopecia
`reversible Nail changes such as hyperpigmentation and
`ridging are commonA partial separation of the nail plate
`onycholysis may occur Nausea
`vomiting anorexia
`diarrhea stomatitis liver function test abnormalities and
`taste sensations may occur but are
`metallic or bitter
`usually mild Hypotension and bradycardia
`during the
`3 hours of infusion have
`been reported but are
`
`first
`
`accumulated
`
`breast cancer
`
`evidence at present shows that women with
`treated with standard regimens do not have
`adverse clinical outcomes with subsequent
`pregnancy
`The effect of the taxanes on pregnancy
`is being studied
`Interestingly a normal male infant was delivered
`post
`administration of paclitaxel during pregnancy per a case
`report from UT MD Anderson Cancer Center
`
`events
`infrequent Significant cardiovascular
`CHF are rare with single agent paclitaxel but patients are
`is combined with cisplatin
`at increased risk if paclitaxel
`
`including
`
`doxorubicin or trastuzumab
`
`are a common side effect of
`Peripheral neuropathies
`paclitaxel and may occur with docetaxel
`especially if high
`cumulative
`are administered Symptoms usually
`doses
`two or months after
`taxane
`discontinuation
`
`resolve
`
`therapy show
`reviews of taxanebased
`Three systematic
`significant benefit in patients with metastatic and node
`positive breast cancer The available data from each of the
`three pooled analyses suggest that docetaxel may be more
`active than paclitaxel especially when given in three
`weekly schedules Studies also indicate
`improved benefit
`in locally advanced and inflammatory breast cancer when
`taxanes are added to their
`regimen Combinations of
`or docetaxel with doxorubicin
`
`epirubicin
`
`paclitaxel
`
`Symptoms may be increased
`neuropathy due
`to diabetes or alcohol
`predisposed
`ingestion Aithialgias and myalgias affect 60 ofpaclitaxel
`lower extremities
`patients primarily in the
`
`in those
`
`patients with
`
`treated
`
`treatment and usually
`beginning two to three days after
`resolving within 2472 hours Arthralia and myalgia are
`infrequent and mild post docetaxel
`
`Colitis is a rare but serious gastrointestinal
`complication
`chemotherapy seen more
`
`associated with taxanebased
`
`frequently seen in patients receiving
`
`docetaxel and with
`
`onset of symptoms at approximately day six of treatment
`Reports by patients of acute abdominal pain could signal
`
`a potentially
`
`fatal colitis
`
`and warrant
`
`aggressive
`
`supportive care
`
`Fluid retention unrelated to cardiotoxicity is a cumulative
`
`in docetaxel
`
`treated patients and
`
`toxicity that may occur
`may be minimized by using the threeday regimen of
`dexamethasone
`to each
`treatment
`Severe
`fluid
`
`prior
`
`retention occurs in up to 65 of patients Fluid retention
`usually appears as peripheral edema but may present
`pleural effusion and usually resolves completely within 16
`weeks of the last docetaxel dose Other docetaxelrelated
`side effects are skin rash andor pruritis palrnarplantar
`hand foot syndrome and epiphora or
`erythrodysesthesia
`hyperlacrirnation watery eyes The latter can occur
`treated with
`result of lacrimal duct stenosis in patients
`dose and resolves
`related to cumulative
`
`as
`
`as a
`
`docetaxel
`
`appears
`after treatment is stopped
`
`In premenopausal women the addition of a taxane to
`standard
`
`adjuvant
`
`anthracyclinebased
`
`does
`
`not
`
`to
`
`a
`
`higher
`produce
`appear
`compared with
`chemotherapy related amenorrhea
`patients who did not receive taxanes In fact taxanes may
`decrease the risk of amenorrhea Women with breast
`
`chemotherapy
`rate of
`
`cancer often express initial worry that
`a subsequent
`risk of recurrence The
`
`pregnancy may increase their
`
`cap ecitabine
`
`gemcitabine
`cyclophosphamide
`in doublets or
`
`have
`
`and
`
`shown
`
`carboplatin
`triplets
`improvement with the addition of the taxane Also the
`
`addition of trastuzumab
`
`to taxanebased
`
`chemotherapy
`
`of
`taxanebased
`increases
`the
`efficicacy
`women with stage 4 HER2positive
`
`breast cancers
`
`regimens
`
`in
`
`The schedule of administration of drugs particularly
`with paclitaxel appears to have an impact on efficacy
`The
`and
`dose
`optimal schedule
`for
`could be 80mgm2week
`the US Food and Drug Administration FDA
`dose and schedule of 175mgm2 IV over
`three weeks In contrast
`three hours every
`the great
`studies were performed using
`majority of docetaxel
`100mgm2 IV given over one hour every three weeks
`
`administration
`
`approved
`
`paclitaxel
`
`rather than
`
`breast cancer
`
`taxane
`
`a gemcitabinepaditaxel
`superiority of this combination over paclitaxel
`line setting Although grade 4 neutropenia
`common with the combination the overall
`both arms were manageable and a quality of life QOL
`indicated better global scores
`for patients
`analyses
`receiving combination therapy
`than for those receiving
`
`in the first
`
`was more
`
`toxicities in
`
`In clinical practice the taxanes are
`single agent paclitaxel
`now standard therapy in metastatic cancer
`
`This article is continued with references and a table in the
`
`Reference
`
`Section
`
`on
`
`the website
`
`supporting
`
`this
`
`briefing
`
`wwwtouchbriefingscom
`
`Significant response and survival benefits were shown in
`two practice changing metastatic
`trialsThe first compared capecitabine 2500 mgm2 x 14
`days + docetaxel 75 mgm2 day one with docetaxel
`three weeks Gastrointestinal
`100mgm2 day one every
`syndrome were more
`hand foot
`events and
`adverse
`common with the combination therapy whereas febrile
`neutropenia sepsis arthralgia and myalgia were more
`common with single agent docetaxel The second phase
`combination showed
`
`III
`
`trial
`
`US ONCOLOGICAL DISEASE 2006
`
`41
`
`