Gynecologic CA.pdf

8/18/2019 Gynecologic CA.pdf

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PSAP-VII • Oncology 129 Gynecologic Cancers

L O

1. Apply knowledge o he pahophysiolog y, eiology,presening sympoms, and diagnosic eva luaion oeach o he g ynecologic cancers o care o paiens.

2. Evaluae he role and limiaions o screening orearly deecion o endomerial and ovarian cancers.

3. Develop a reamen plan or a paien wih a newlydiagnosed gynecologic cancer.

4. Assess he role o consolida ion reamen and heimpac on overall survival o paiens wih gyneco-logic malignancies.

5. Develop an algorihm or he selecion o a che-moherapy regimen or he reamen o recurrengynecologic malignancies.

ITe gynecologic cancers remain a pharmacohera-

peuic challenge. In general, he primary and mos effec-ive reamen is surgery i he cancer is diagnosed in heearly sages. Boh endomerial and cervical cancers aremore likely o be diagnosed in he early sages because oheir sympoms and he availabiliy o effecive screen-ing ools. Regretably, ovarian cancer is denoed he“silen ki ller” among he gy necologic cancers because i

is ofen no diagnosed unil an advanced sage when acure is di fficul. Tis chaper describes he reamen oendomerial, ovarian, and cervical cancers. Vaginal and

vulvar cancers are no discussed in his chaper; how-

ever, he reamen approaches used in he managemeno cervical cancer can generally be applied o vaginal or vulvar cancers. Overall, he eiology o gynecologic cancers is no

well undersood. wo excepions are he disinc asso-ciaions beween human papillomavirus (HPV) inec-ion and developmen o cervical cancer; and herediarynonpolyposis colorecal cancer (HNPCC) or Lynchsyndrome, which increases he risk o boh ovarian andendomerial cancers. Box 1-1 liss risk acors or hehree gynecologic malignancies. Wih all hree gynecologic malignancies, paiens are

generally asympomaic in he early sage o disease, wih sympoms appearing as he cancer progresses . Alhough he sympoms o ovarian cancer are nonspe-cific and have an insidious onse ofen leading o delayin diagnosis, posmenopausal bleeding associaed wihendomerial cancer and poscoial bleeding and painassociaed wih cervical cancer resul in women seek-ing gynecologic care and obaining an earlier diagnosis.Box 1-2 liss common presening sympoms.

G C

B J A. S, P.D., FCCP, FISOPP, BCOP

Reviewed by Dayna L. McCauley, Pharm.D., BCOP; Anne L. Hume, Pharm.D., FCCP, BCPS;and Helen M. LoSasso, Pharm.D., BCPS

B R RTe goal o PSAP is o provide only he mos recen (pas 3–5 years) inormaion or opics. Chapers do no provide an overall review. Suggesed resources or background inormaion on his opic include:• Smih JA, Wol J. Ovarian cancer. In: DiPiro J, alber RL, Yee GC, Mazke GR, Wells BG, Posey LM, eds.

Pharmacoherapy: A Pahophysiologic Approach, 7h ed. Boson: McGraw-Hill, 2008: 2245–58.• Mach CM, Clouier L. Endomerial cancer. In: Borgel LM, O’Connell MB, Smih JA, Calis K, eds. Women’s

Healh Across he Liespan: A Pharmacoherapeuic Approach. Behesda: American Sociey o Healh-Sysem Pharmaciss, 2010:721–34.

• Smih JA. Cer vical cancer. In: Borgel LM, O’Connell MB, Smih JA, Calis K, eds. Women’s Healh Acrosshe Liespan: A Pharmacoherapeuic Approach. Behesda: American Sociey o Healh-Sysem Pharmaciss,2010:749–60.


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PSAP-VII • Oncology130Gynecologic Cancers

For ovarian cancer, he diagnosis and sage are con-firmed during he iniial surgery because he umors areofen difficul o access, and perioneal seeding can occur

i a needle biopsy is perormed beore surgery. Alhough boh cerv ical and endomerial cancer diagnoses can beconfirmed rom biopsy, saging or endomerial canceris a combinaion o diagnosic ess and surgical exami-naion, whereas advanced cervical cancer is mos ofensaged by diagnosic ess alone. Because mos womenundergo surgery as par o heir primary reamen, hesaging work-up is compleed during surgery. All gyne-cologic cancer saging is classified by he InernaionalFederaion o Gynecology and Obserics (FIGO) sag-ing sysem, which is described in deph in he baselinereview reerences. Tis saging sysem requires exen-

sive surgery and exper pahological review. I is rec-ommended ha a rained gynecologic oncology sur-geon complee he umor-debulking surgery and sag-ing when cancer is suspeced in order o preven under-saging and o improve he overall oucome.

Al l hree gy necologic cancers may spread by direcexension o surrounding organs (e.g., vagina, ovaries,uerus, allopian ubes, bladder, recum, pelvic peri-oneum). Anoher primary mechanism o measasisis hrough he lymphaic sysem, ypically involvinghe pelvic and para-aoric lymph nodes, which may beenlarged upon palpaion. Ovarian cancer may also dis-seminae hroughou he perioneum hrough he peri-oneal fluid. umor cells hen are able o adhere o andinvade abdominal and/or pelvic organs, resuling in dis-seminaed disease a disan sies such as he surace ohe diaphragm or liver, as well as pulmonary and pleuralinvolvemen. Finally, disan measasis may occur romspread o cancer cells hrough he hemaogenous roue. When diagnosed in early sages, inervenions areofen curaive wih a minimal impac on qualiy o lie.Similar o mos cancers, a delay in diagnosis unil a moreadvanced sage o disease is associaed wih a muchpoorer prognosis. In general, progressive and recurren

gynecologic cancers are associaed wih inheren oracquired drug resisance and have a poor prognosis(5-year survival o less han 20%).

Oher consideraions ha influence prognosisinclude umor grade, hisology, age, race, endocrinesaus, deph o umor invasion, exension o disease

wihin he pelvic cavi y, presence o posiive lymphnodes, and presence o disan measases. In addiion,he success o he primary surgery o achieve opimalumor reducion (less han 1 cm o deecable disease)is a significan prognosic acor, especially or ovariancancer. Furhermore, reamen o advanced and recur-

ren disease is ofen associaed wih complicaions haaffec he overall qualiy o lie (e.g., fisulas, neuropa-hies, permanen damage o he bowel).

E C

Endomerial or uerine cancer is he mos commongynecologic cancer in he Unied Saes, wih morehan 43,470 esimaed new cases annually. Among hegynecologic cancers, i has he bes prognosis wih onlyabou 7950 (18.2%) deahs annually.

A T C

CA Cancer anigenFIGO Inernaional Federaion o

Gynecology and ObsericsGOG Gynecologic Oncology GroupHNPCC Herediary nonpolyposis

colorecal cancerHPV Human papillomavirusIDMS Isoope diluion mass

specromery VUS ransvaginal ulrasonography

Box 1-1. Risk Facors or Gynecologic Cancers

Endometrial Cancer Arican American raceHerediary nonpolyposis colorecal cancerInsulinemiaNon–insulin-dependen diabees

Nullipariy Obesiy amoxienUnopposed esrogen herapy

Cervical CancerHuman papillomavirus inecionImmunosuppressionMuliple sexual parnersOher sexually ransmited diseasesSmokingUnproeced sexual aciviy Use o oral conracepives

Ovarian CancerEarly menarche (beore age 12 years)Feriliy drugsHerediary breas/ovarian cancer – BRCA1, BRCA2Herediary nonpolyposis colorecal cancerIneriliy Lae menopause (afer age 60 years)Nullipariy Obesiy

Wesern/developed counries


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Etiology

Te eiology o endomerial cancer has no been ully

deermined. Te risk o endomerial cancer is associ-

aed wih eiher amily hisory or acors ha conrib-

ue o increased exposure o esrogen and is meabo-

lies. Obesiy is considered a major risk acor or endo-merial cancer. Women wih an excess 13–23 kg o body

weigh have an associaed 3- o 5-old greaer risk o

developing endomerial cancer compared wih he gen-

eral populaion. Obesiy is associaed wih a higher per-

cenage o adipose issue, which is where he conver-

sion o androgens o esrogens occurs hrough several

pahways including he aromaizaion o androsene-

dione o esrone. Te ne resul is increased esrogen

exposure ha resuls in an increased risk o endomerial

hyperplasia and ulimaely he poenial or progressiono invasive endomerial cancer.

Oher condiions associaed wih an increased riskare polycysic ovarian syndrome, a hyperesrogenicsae; and HNPCC, which is associaed wih a 40% o60% increased risk o developing endomerial cancer.

Alhough primari ly an aniesrogen, amoxien use has

also been associaed wih an increased risk o endome-rial cancer because o is mixed esrogenic effecs onhe endomerial l ining.

Women wih a known herediary risk should haveannual screening afer age 35, bu here is no sandard-ized algorihm, so screening should be based on clini-cal judgmen. Women receiving amoxien who sillhave a uerus are also a an increased risk o developingendomerial cancer and should have annual screening

while on herapy and or a leas 1 year afer compleiono herapy. Annual screening may include pelvic exam-inaion, ransvaginal ulrasonography (VUS), pelvic

ulrasonography, and endomerial biopsies as indicaed(e.g., or irregular bleeding). For women wihou riskacors, rouine screening is no recommended.

Diagnosis Alhough he diagnosis o endomerial cancer can be

confirmed rom biopsy, saging or endomerial canceris based on a combinaion o diagnosic ess and sur-gical examinaion. When women presen wih irregular

vaginal bleeding and here is a suspicion o endomerialcancer, an endomerial biopsy is usually perormed dur-ing an office visi. I he biopsy is negaive, hen a dila-

ion and curetage is compleed o gaher beter sam-pling and confirm clinical findings. A posiive biopsyis ofen ollowed up by a VUS o deermine endome-rial hickness; i i is more han 4–5 mm, i requires ur-her evaluaion. A cervical biopsy should be perormedi cervical invasion is a concern. Hyseroscopy may also

be included in he iniial work-up o inspec he uer-ine caviy or polyps and visualizaion o he endome-rium, and is ofen done in conjuncion wih dilaionand curetage. Once a diagnosis is reached, he exeno disease in oher pelvic organs and beyond he pelviccaviy is deermined by diagnosic modaliies such ascysoscopy, procoscopy, compued omography (C),and magneic resonance imaging (MRI) as appropriae.

TreatmentTerapeutic Goals

Early sage endomerial cancer can be cured wihimely and aggressive reamen involving surgery,chemoherapy, and/or radiaion. Terapeuic goals inrecurren and measaic cancer are o alleviae symp-oms and decrease disease progression. Te achieve-men o sable disease is ofen considered a reasonableherapeuic goal or recurren gynecologic cancers.

Box 1-2. Clinical Presenaion o GynecologicCancers

Endometrial Cancer Abdominal u llness/pressure Abnormal vaginal bleeding• Pre- or perimenopausal woman: heavy or prolonged

vaginal bleedi ng• Posmenopausal woman: resumpion o vagi nal

bleeding

Cervical Cancer Abnormal Papan icolaou smear Abnormal vaginal bleeding Abnormal vaginal dischargeDifficul bowel movemensFlank painHemauriaPoscoial vagina l bleedingPain during/afer inercourseUnilaeral hip, butock, leg painUrinary requency

Ovarian Cancer Weigh change Abdominal discomor/disenion Abdominal u llness/bloaingEarly saiey Indigesion/reflux NauseaChange in bowel habis (flaulence, diarrhea, or

consipaion) Ascies Abdominal pain

Urinary urgency/requency Irregular vaginal bleedingElevaed cancer anigen (CA)-125 (normal

concenraion less han 35 unis/mL)


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Surgery and RadiationSurgery is he primary reamen or early sage endo-

merial cancer. Tis should include a horough paho-logic assessmen o he deph o myomerial invasion inrelaion o he overall myomerial hickness, umor sizeand locaion wihin he uerus, hisology and grade, andexen o any lymphaic invasion. Afer complee resec-

ion o all disease (including a vaginal or oal hyser-ecomy and bilaeral salpingo-oophorecomy), pelvic washings are necessary o complee surgical sag-ing. Alhough associaed wih some conroversy, pelvicand/or para-aoric lymphadenecomy is a precise mehodor ideniying nodal measases and has been associaed

wih improved survival raes in endomerial cancer.Radiaion alone is a reamen opion o consider in

paiens who are medically inoperable because opera-ive risk is high. Morbid obesiy and severe cardiopul-monary disease are he mos common reasons a paien

wih endomeria l carcinoma is deemed medica lly inop-erable. More ofen, radiaion is an adjuvan o eihersurgery or chemoherapy. Afer surgery, paiens mayreceive inernal radiaion herapy (brachyherapy) incombinaion wih exernal beam radioherapy whenhere is lymph node involvemen or oher eaures haplace he paien a high risk o recurrence. In recenclinical rials, he use o adjuvan radiaion in paiens

wih sage I/II low- and inermediae-risk diseaseresuled in reduced local and regional recurrence buhad no impac on overall survival.

Adjuvan radiaion herapy is also warraned inpaiens wih high-grade umor and increased deph oumor invasion in he myomerium, lymphovascular

space invasion, large umor volume, and involvemen ohe lower uerine segmen or cervi x. Alhough he addi-ion o radiaion does no improve overall survival, ireduces he risk o recurrence by 50%. Te decision orea depends on wheher paiens have any o he riskacors associaed wih disease discussed above andpaien acors such as age, body weigh (obesiy), andcomorbidiies. Finally, mos recurrences o endomerialcancer are wihin he vaginal vaul and may be reaed

wih salvage exernal beam radiaion wih or wihou vaginal brachy herapy.

Drug TerapyUnil recenly, chemoherapy has no played a role inhe primar y reamen o endomerial cancer. Alhoughclinical rials have demonsraed improved raes ocomplee response and progression-ree survival andnew regimens are beginning o emerge, mos o he cur-ren regimens have been esablished hrough clinicalpracice experience. Hisorically, doxorubicin wih or

wihou cisplain has demonsraed an increased overallresponse rae and progression-ree sur vival or paiens

wih early sage disease. Unorunaely, chemoherapyhas had no impac on overall survival in paiens wih

advanced sages o endomerial cancer. Te combina-ion o pacliaxel, doxorubicin, and cisplain or firs-linereamen o advanced endomerial cancer did improveprogression-ree and overall survival, bu he oxiciyassociaed wih his regimen has limied is clinical use.

Alhough a sandard or firs-line chemoherapy has yeo be idenified or measaic or recurren endomerial

cancer, muliple phase II sudies have suggesed hapacliaxel plus carboplain is a well-oleraed regimen,and i is commonly used in he reamen o endomerialcancer.

Chemoherapy or recurren endomerial cancer con-siss o eiher a single agen or a combinaion o agens

wih or wihou radia ion herapy. Single-agen regi-mens include gemciabine, doxorubicin, cisplain, car-

boplain, opoecan, and paclia xel (able 1-1). Pacli-axel/carboplain, gemciabine/cisplain, and gem-ciabine/carboplain have demonsraed an improve-men in progression-ree survival. Iosamide and vin-

crisine have moderae aciviy bu also significan ox-iciies, so hese agens are used primarily or sarcoma-ous and endomerioid hisologies. Hormonal agens are commonly used or he rea-men o endomerial cancer and are ypically seleced

based upon he hormone recepor expression o heumor (i.e., progeserone or esrogen recepor). Hor-monal agens are atracive or he managemen o recur-ren disease in paiens wih esrogen- or progeserone-posiive umors because hey are adminisered orallyand are generally well oleraed. Megesrol aceae ormedroxyprogeserone can be used or recurren endo-

merial cancer. Paiens should receive he lowes effec-ive dosage o hormonal agen o limi oxiciy. Te useo amoxien and aromaase inhibiors has been limied

because o low response raes (9% o 14%) and an esi-maed progression-ree inerval o 1–6 monhs. Luein-izing hormone–releasing hormone and gonadoropin-releasing hormone recepors are presen in endomerialcancer issue and have he abiliy o indirecly inhibiesrogen pahway (negaive eedback), bu he overallresponse raes have no been impressive (see able 1-1).

PreventionSome liesyle choices offer a proecive mechanism

and lower he risk o developing endomerial cancer.Firs, imely and proper medical reamen should besough or precursor disorders o he endomerium odecrease he opporuniy or progression o endome-rial cancer. Women should avoid he use o unopposedesrogens in he presence o an inac uerus, and all

women should avoid long-erm hormone herapy. Cau-ion is also recommended wih he use o phyoesro-gens because heir long-erm saey is unknown. Finally,appropriae die and exercise inervenions are impor-an o decrease he risk o obesiy.


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Table 1-1. Chemoherapy or reamen o Gynecologic Cancers

Drug(s) Dosage Cycle Frequency

Combination Regimens

Pacliaxel andcarboplain

175 mg/m2 IV (3-hr in usion) AUC 5–7.5 IV

Every 21 days

Pacliaxel andcisplain

135 mg/m2 IV (24-hr in usion)75 mg/m2 IV

Every 21 days

Pacliaxel andcisplain

135 mg/m2 IV over 24 hours on day 1 and 100 mg/m2 IP over 1 hour on day 260 mg/m2 IP over 1 hour on day 8

Every 21 days

Cisplain andcyclophosphamide

50–100 mg/m2 IV 500–1000 mg/m2 IV

Every 21–28 days

Cisplain wih radiaion 40 mg/m2 IV (cap a 70 mg) weekly 5 weeks oal

Cisplain and fluorouracil wihradiaion

40 mg/m2/day IV daily or 4 days250 mg/m2/day daily or 4 days

Every 21 days

Doceaxel andcarboplain

75 mg/m2 IV AUC 5 IV

Every 21 days

Gemciabine and

carboplain

800 mg/m2 IV days 1 & 8

AUC 5 IV day 1

Every 21 days

Gemciabine andcisplain

800 mg/m2 IV days 1 and 840 mg/m2 IV days 1 and 8

Every 21 days

Liposomal doxorubicin andcarboplain

30 mg/m2 IV over 1–3 hr AUC 5 IV

Every 28 days

Cyclophosphamide and bevaci zumab

50 mg PO once daily 10 mg/kg IV days 1 and 5

Every 28 days(coninuous)

opoecan andcisplain

0.75 mg IV days 1, 2, and 350 mg/m2 IV day 1 only

Every 21 days

Iosamide anddoxorubicin

1500 mg/m2/day coninuous IV i nusion or 3 d ays30 mg/m2/day coninuous IV i nusion or 2 d ays

Every 21 days

Single Agents

Doceaxel 75 mg/m2 IV Every 21 daysLiposomal doxorubicin 40 mg/m2 IV Every 28 days

Gemciabine 800–1000 mg/m2 IV days 1, 8, and 15 Every 28 days

Pacliaxel 60–80 mg/m2 I V (1-hr inusion) Every week

Pacliaxel 135–175 mg/m2 I V (3-hr inusion) Every 21 days

Carboplain AUC 5–7.5 IV Every 21–28 days

Cisplain 50–75 mg/m2 IV Every 21–28 days

Iosamide 1500 mg/m2/day or 3–5 days Every 21 days

opoecan 1.3–1.5 mg/m2 IV days 1–5 Every 21 days

opoecan 4 mg/m2 IV days 1, 8, and 15 Every 28 days

Eoposide 50 mg/m2 PO once dai ly days 1–10 Every 21–28 days

Capeciabine 1800-2000 mg/m2

PO in d iv ided doses wo i mes/day or 2 weeks Ever y 21 days Al ream ine 260 mg/m2 PO divided ino our doses/day or 14–21 days Every 28 days

Hormonal Agents

amoxien 20 mg PO wo imes/day Coninuous

Lerozole 2.5 mg PO once daily Coninuous

Medroxyprogeserone 200–400 mg PO in divided doses wo imes/day Coninuous

Megesrol aceae 40 mg PO our imes/day Coninuous

Leuprolide 3.75 mg IM Monhly

AUC = area under he cur ve (mg/L*h); carboplain dose hen calculaed based on Calver ormula (carboplain dose = [GFR+25] AUC);IM = inra muscularly; IP = inr aperioneal; IV = inravenous; PO =orally.


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C C

Alhough cervical cancer is he second mos com-mon cancer in women worldwide, i is he leas commonamong gynecologic malignancies in he Unied Saes

wih only 12,200 esimaed new cases in 2010. I is associ-aed wih moderaely high moraliy (34.5%). Mos caseso cervical cancers occur in developing counries (morehan 85%) because o he limied availabiliy o advancedscreening echniques.

EtiologyCervical cancer is he mos prevenable o gynecologic

cancers and is considered a cancer caused by unavorable behaviors including smoking, muliple sexual parners,and unproeced sexual aciviy. Human papillomavirusinecion causes virually all cervical cancer. OncogenicHPV gains access o he basal layer o epihelium hroughmicroraumas ha occur commonly during inercourse.Because HPV replicaes in a non-lyic (no associaed

wih cell deah) manner in he ineced basal cells, i doesno cause release o pro-inflammaory cyokines andexiss in he cervical basal cell layer in he absence o aninnae immune response. Tis allows or persisen inec-ions, which can lead o he developmen o precancerousand cancerous lesions in suscepible paiens. In addiion o HPV inecion, he mos commonconribuing risk acor or cervical cancer is he use oobacco producs. Nicoine and is acive meabolie,coinine, may affec muliple pahways leading o cancerand have been associaed wih meaplasia, angiogenesis,and prolieraion in epihelial cells. Boh nicoine and

coinine have been deeced in cervical mucus, confirm-ing ha hese and oher carcinogens presen in obaccosmoke are carried by he blood o he cervix. Tese car-cinogens are associaed wih inducion o cellular andDNA damage and he ormaion o chemically sableDNA adducs ha promoe geneic insabiliy wihin hecervical epihelium.

ScreeningTe inroducion o he Papanicolaou es (Pap smear)

ino clinical pracice and he improvemen in access oand adherence wih cervical cancer screening guide-

lines have been associaed wih a 74% reducion in heincidence o cervical cancer. Screening or cervical can-cer should begin abou 3 years afer he onse o vaginalinercourse bu no laer han 21 years o age. Screeningconsiss o an annual Pap smear and pelvic examinaion.Recen updaes o he American Congress o Obse-rics and Gynecology screening guidelines recommendha when a woman beween 21 and 30 years old wih-ou known risk acors or cervical cancer has had hreeor more consecuive annual examinaions wih normalfindings, he Pap smear may be perormed less ofen,once every 2 years, a he discreion o her gynecologis.

However, women wih one or more high-risk acorsshould coninue cervical cancer screening wih an annualPap smear and pelvic examinaion. Afer age 30, HPVesing should be compleed once and repeaed when-ever an abnormal Pap smear occurs or periodically in a

woman who has muliple sexual parners. Serological HPV ess canno disinguish beween

pas and curren inecions; hereore, curren inecionscan only be deeced hrough idenificaion o viral DNAin clinical samples. Tis requires sensiive-ype specificHPV DNA ess. wo ess are used in clinical pracice

wih he abiliy o deec 13 high-risk HPV ypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). TeHPV ess canno disinguish he subype(s) o HPV

bu are quaniaive or he viral load presen. esing iscompleed on he Pap smear sample. No effecive rea-men is available o eradicae HPV inecions. A woman

wih a diagnosis o a high-risk HPV inecion should beclosely moniored wih Pap smears every 6 monhs, wihhe addiion o a colposcopy examinaion i a Pap smearis abnormal, o preven progression o cervical cancer.

DiagnosisBecause he Pap smear is an effecive screening ool

or cervical cancer, mos cases o cervical cancer aredeeced as precancerous lesions. Once an abnormal Papsmear is repored, ollow-up is recommended. For earlysigns such as aypical cells or mild dysplasia, he recom-mended ollow-up is a repea Pap smear wihin 6 monhs.However, or higher-grade lesions, he recommended ol-low-up includes colposcopy examinaion wih endocer-

vical curetage and biopsies. When cervical cancer is con-

firmed in biopsy samples, addiional diagnosic ess arerequired (e.g., blood ess; imaging by C, MRI, or posi-ron emission omography) o evaluae he exen o dis-ease. Hisology is also deermined rom he biopsy sam-ples; mos are squamous cell carcinomas, ollowed byadenocarcinomas, and rarely neuroendocrine or smallcell carcinomas.


Early sage cervical cancer can be cured wih imelysurgery. Recurren and measaic cervical cancer does

no respond well o chemoherapy; he primary goalo reamen is palliaion o sympoms and conrollingumor growh and progression. Sable disease is ofenconsidered a reasonable herapeuic goal or any recur-ren gynecologic cancer.

Surgery and Radiation TerapySurgery is reserved or early sage cervical cancer (i.e.,

eiher FIGO sage IA or IB1 disease), when i is possible o compleely excise he umor wih negaive mar-gins. Surgery includes a hyserecomy (simple or radical)

wih pelvic and/or para-aoric lymph node dissecion.


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Alhough his is a definiive reamen o he cervicalcancer, i eliminaes he possibiliy or reproducion.

Hence, paiens wih sage IA disease may seek eriliy-sparing surgical inervenions such as a radical rachelec-omy (removal o he cervix and paramerium) and lap-aroscopic lymphadenecomy. A radical rachelecomy isa more complicaed procedure han a hyserecomy and

requires a skilled surgeon or a successul oucome.

When here is an isolaed recurrence wihin a previ-ously radiaed field, a procedure called an exeneraionmay be considered. Tis surgery involves muliple pro-cedures o remove he umor and any adjacen organs apoenial risk o microscopic invasion. oal pelvic exen-eraion involves he removal o he bladder, descend-ing colon, recum, uerus, ovaries, allopian ubes, and

vagina; wo somas are placed or urine and ecal elim-inaion. In an anerior exeneraion, he colon and rec-um are no removed and only one soma is placed orurinary eliminaion. Finally, in a poserior pelvic exener-aion, he bladder is no removed, and only a colosomyis placed. When easible and clinically appropriae, he

vagina is rebuil o enable sexual inercourse. Exenera-ion has a significan impac on qualiy o lie. An exen-sive diagnosic imaging and workup is compleed o ver-iy no measases beore embarking on exeneraion.

Radiaion herapy is mos ofen used in combinaion wih chemoherapy. Specifically, radiaion plus weeklycisplain is considered he sandard o care or locallyadvanced and measaic cervical cancer sages IIB, IIIA,IIIB, and IVA. Te chemoradiaion regimen includes cis-plain 40 mg/m2/week (maximum o six doses) concur-renly while receiving 45 Gray (Gy) o exernal beam

pelvic radiaion. Tis is ollowed by inernal radiaion(brachyherapy), mos ofen adminisered hrough afer-loading andem and ovoid inserion or 72 hours or high-dose inracaviary brachyherapy.

ChemotherapyCisplain is more effecive in cervical cancer han car-

boplain. As a resul, unlike oher gynecologic cancers,he subsiuion o carboplain or cisplain o decreaseoxiciy is no well acceped or recommended. Use ochemoherapy alone is reserved or recurrences wihinhe radiaion field or where he desired oucome is he

relie o sympoms. Firs-line reamen wih chemoher-apy alone is appropriae in paiens wih sage IV disease because chemoradiaion is no curaive. Similar o ohergynecologic cancers, single-agen plainum-based her-apy has been he sandard o care; however, new clinicalrial daa suppor he use o combinaion plainum-basedregimens. opoecan plus cisplain is one o he ew com-

binaions wih approved U.S. Food and Drug Adminisra-ion (FDA) labeling or recurren cervical cancer. Oncehe disease progresses and becomes plainum resisan,here is no sandard o care or chemoherapy. Dependingon physician preerence, residual oxiciies, and paien

preerence, any one o he non-plainum chemoherapyagens lised in able 1-1 may be considered.

PreventionCervical cancer is almos compleely prevenable. Te

mos successul approach or prevenion is absinencerom any sexual aciviy; however, his is unrealisic o

coninue hroughou lie. Muual monogamy and con-doms are less effecive or prevening cervical cancer.

Alhough a couple may achieve muual monogamy, oneor more previous parners may have provided exposureo HPV. Each addiional parner adds anoher 25% o herisk o HPV exposure. A mea-analysis evaluaing he useo condoms o preven HPV inecion demonsraed alack o published sudies regarding condom use and HPVinecion. Limied evidence suppors a proecive effeco condom use on HPV DNA deecion, and some sud-ies acually show an increased incidence o HPV lesions

wih condom use.

Te HPV quadrivalen vaccine (agains ypes 6, 11,16, and 18) and he bivalen HPV vaccine (agains ypes16 and 18) are boh indicaed or prevening HPV inec-ion and reducing he risk o developing cervical cancer.o be effecive, he HPV vaccine should be adminisered

beore any poenial exposure o he virus (i.e., beore anysexual aciviy). However, i is also effecive in individuals

who have been sexually acive and es negaive or HPV.Neiher o he vaccines is effecive or reamen o HPVinecions or cervical cancer. Te quadrivalen HPV vaccine has limied cross-neu-ralizaion abiliy agains oher HPV genoypes. Prelimi-

nary daa rom ollow-up clinical sudies sugges ha heimmuniy achieved rom he HPV vaccine is no likely o

be lielong. Addiional sudies are needed o deerminehe iming or boosers or wheher repeaing he series isnecessary. Te HPV vaccine is effecive or a leas 5 yearsor HPV-16, bu addiional evaluaion o deermine heeffecive geomeric ier is needed. In one sudy, he HPV-18 iers in paiens reaed wih he vaccine increased ini-ially bu were a concenraions similar o he geomericiers in he placebo group by 36 monhs afer vaccina-ion. Te hree-sho series mus be compleed wihin he6-monh ime rame or an adequae geomeric ier o be

achieved. Te reduced efficacy in hose no compleinghe ull hree-sho series is sill a concern. Te rue impaco he use o he HPV vaccines on he prevenion o cervi-cal cancer will no be apparen or decades.

O COvarian cancer is he mos deadly o he gynecologic

malignancies in he Unied Saes. I is he fifh leadingcause o cancer-relaed deahs in women and has a mor-aliy rae o more han 60%. An esimaed 21,880 newcases in Unied Saes are diagnosed annually. Tis high


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moraliy rae can be atribued o he lae sage o diag-nosis and o inheren drug resisance.

EtiologyTe eiology o mos cases o ovarian cancer remains

unclear and unpredicable. Te wo primary heories arehe incessan ovulaion hypohesis and he gonadoropin

hypohesis. Boh hypoheses are based on he premiseha an increasing number o ovulaions or prolieraionso he ovary epihelium leads o an increased poenialor aberran cell repair and muaions, which is hougho evenually lead o he ormaion o cancer. Anoherheory suggess ha chronic inflammaion rom use oalc producs or asbesos exposure is a conribuing ac-or; however, his associaion has no been confirmed inlongiudinal epidemiology sudies. Ovarian cancer is considered a sporadic cancer, wihless han 10% o all cases being atribued o herediaryrisk. However, i more han one firs-degree relaive (e.g.,a moher and siser) is affliced wih ovarian cancer, herisk increases o more han 50%.

Te umor suppressor genes BRCA1 and BRCA2 arehough o be involved in one or more pahways o DNAdamage, including boh he recogniion and repair ogenes associaed wih developmen o ovarian cancer.O he wo genes, BRCA1 is more prevalen, being asso-ciaed wih 90% o inheried and 10% o sporadic caseso ovarian cancer. Paiens wih BRCA1-associaed ovar-ian cancer are usually younger and he umors are moreaggressive wih moderae o high grade, serous hisology.Te wo mos common geneic abnormaliies o amilialovarian cancer are herediary breas/ovarian cancer syn-

drome and herediary HNPCC. Herediary breas/ovar-ian cancer syndrome is associaed wih germ-line mua-ions in BRCA1 and BRCA2 and wih earlier onse o can-cer and ofen muliple cancers in he same paien. TeBRCA muaions have also been associaed wih Ashke-nazi Jewish ancesry. Te HNPCC syndrome has also

been associaed wih up o 12% o herediary ovarian can-cer cases. In paiens esing posiive or HNPCC geneicmuaions, ovarian cancer occurs a an earlier age hanin he general populaion, and hese paiens are morelikely o have a synchronous endomerial cancer. In addi-ion, he cancer is more likely o be well or moderaely

differeniaed. Supporing he wo primary hypoheses o he devel-opmen o ovarian cancer, condiions ha increase heoal number o ovulaions in women’s reproducive his-ory also have been idenified as risk acors or ovariancancer (see Box 1-1).

Unlike cervical cancer, ovarian cancer does no havea known pre-invasive componen or premalignan pro-cess. Hence i is difficul o screen paiens o deecearly disease. Large-scale clinical sudies have ailed odemonsrae a benefi or rouine screening using can-cer anigen (CA)-125 concenraions or VUS in he

general populaion. However, in women wih a posiiveamily hisory who are a high risk o ovarian cancer, heNaional Insiues o Healh recommends monioring

wih an annual pelvic examinaion, CA-125 concenra-ion, and VUS every 6 monhs.

Diagnosis

Early disease is ypically asympomaic. As he diseaseadvances, paiens experience nonspecific sympomsofen conused wih sympoms o common benign gas-roinesinal disorders (see Box 1-2). Tis ofen resuls indelays in seeking a gynecologic examinaion and in diag-nosis. A key elemen or improving paien oucomes in

women wih ovarian cancer is he educaion o he pub-lic and oher healh care providers. Women mus seekmedical atenion earlier when experiencing any o henonspecific sympoms described above or more han 6

weeks. During a gynecologic examinaion, signs ha indi-

cae he need or urher esing include presence o anadnexal mass or any irregulariy, solid eaures, and nod-ulariy o he ovary. Paiens wih advanced disease mayexhibi signs o abdominal disension because o asci-es and increased umor burden, or dyspnea or cough

because o pleural effusions.In addiion o a physical examinaion, a complee blood

coun, chemisry profile including liver and kidney unc-ion ess, and ess or umors markers including CA-125and CA-19 concenraions should be perormed o sup-por diagnosis. Te CA-125 marker is a nonspecific ani-gen bu is currenly he bes umor marker or epihelial

ovarian carcinoma. A normal CA-125 concenraion isless han 35 unis/mL; when elevaed a he ime o diag-nosis, changes in CA-125 concenraions correlae wihresponse and progression. Te CA-125 concenraionsmay also be elevaed in benign condiions such as dur-ing ovulaion and/or menses, divericuliis, and endome-riosis. Oher nongynecologic cancers may also produceelevaions in he marker. o urher evaluae he exen odisease and confirm he diagnosis, oher diagnosic essmay include VUS or abdominal ulrasonography, gas-roinesinal evaluaions, ches radiography, C, MRI, orposiron emission omography.


Early sage ovarian cancer can be cured wih imely andaggressive reamen involving surgery, chemoherapy,and/or radiaion. In many cases, women wih advancedovarian cancer may achieve a complee response o ini-ial surgery and chemoherapy alhough more han 75%o hese cancers will recur wihin he firs 2 years. Inrecurren or measaic ovarian cancer, he primary goalo reamen is palliaion o sympoms and conrollingumor growh and progression. Sable disease is ofen


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considered a reasonable herapeuic goal or recurrenovarian cancer.

Surgery and Radiation TerapySurgery is he primary reamen inervenion or ovar-

ian cancer; i also confirms he diagnosis and saging. Sur-gery is ofen curaive or paiens wih sage IA disease,

wih long-erm survival exceeding 90%. Te surgical rea-men or ovarian cancer includes a oal abdominal hys-erecomy wih bilaeral salpingo-oophorecomy, omen-ecomy, and lymph node dissecion. Te primary objec-ive o surgery is o opimally debulk he umor o lesshan 1 cm o deecable residual disease. Opimal cyore-ducion is associaed wih higher complee response raeso chemoherapy and longer overall survival.

Addiional surgery afer compleion o chemoher-apy is reerred o as secondary cyoreducion or inervaldebulking i ollowed by addiional cycles o chemoher-apy. Cyoreducion is hough o aciliae he response

o chemoherapy and improve overall survival. However,randomized rials o secondary surgical cyoreducionhave repored conflicing resuls. Curren clinical prac-ice is no sandardized and remains conenious. Also conroversial is second-look surgery, which is per-ormed in paiens wih a clinical complee response aferprimary chemoherapy. Te purpose is o examine heperioneal caviy or any visible or microscopic diseaseo deermine wheher addiional chemoherapy is war-raned. However, his procedure has no been shown oimprove overall survival, and abou 50% o paiens wiha negaive second-look surgery sill relapse. Finally, sur-

gical inervenions are considered in paiens wih recur-ren disease o improve qualiy o lie by relieving symp-oms associaed wih complicaions (e.g., small bowelobsrucion). Radiaion has no impac on overall survival whenused in early sage disease. Is primary role is or pallia-ion o sympoms in paiens wih recurren pelvic dis-ease, which is ofen associaed wih small bowel obsruc-ion. Eiher exernal beam whole-abdominal irradiaion

wih 35–45 Gy or inraperioneal isoopes such as 32P can be used in he managemen o ovarian cancer o alleviaesympoms; hese are associaed wih an improvemen inhe woman’s qualiy o lie.

Chemotherapy Primary reatment

Conroversy exiss regarding he sandard rea-men or FIGO sage IA and IB ovarian cancer. Manyclinicians rea wih hree o six cycles o pacliaxel andcarboplain because o he high risk o recurrence. Tesandard reamen or paiens wih FIGO sage IC–IVdisease or incomplee saging is six o eigh cycles o aaxane plus plainum agen, mos ofen carboplain andpacliaxel (see able 1-1).

Despie being included in guidelines rom heNaional Comprehensive Cancer Nework andNaional Cancer Insiue, he roue o adminisraionremains conroversial in clinical pracice. Adminisra-ion o chemoherapy hrough inraperioneal deliv-ery is a no a new concep; however, phase III rialsinvesigaing inraperioneal herapy conduced in he

pas decade have brough he inraperioneal/inrave-nous issue back o he clinical arena. Tree random-ized phase III sudies evaluaing he role o inraperi-oneal chemoherapy in ovarian cancer demonsraedan improvemen in progression-ree survival. In worials, he improvemen in overall survival was smalland was associaed wih more oxiciy. Tus, hese regi-mens did no ranslae ino clinical pracice. Te Gyne-cologic Oncology Group (GOG) rial 172, publishedin 2006, was he firs o demonsrae an improvemenin overall survival as well. Tis sudy compared inra-

venous pacliaxel and inravenous cisplain (inrave-nous group) wih inravenous pacliaxel over 24 hourson day 1 ollowed by inraperioneal cisplain on day2 and inraperioneal pacliaxel on day 8 (inraperio-neal group) in paiens wih opimally debulked sageIII ovarian cancer. Te median duraion o overall sur-

vival was higher in he inraperioneal group han inhe inravenous group (65.6 monhs vs. 49.7 monhs).Te qualiy o lie was significanly worse or paiensin he inraperioneal group during herapy because oincreased nausea, vomiing, dehydraion, elecrolyeabnormaliies, inecion, and neuropahy. However, by6 weeks afer compleion o chemoherapy, no differ-ences in qualiy o lie were observed.

Appropriae paien selecion is criical or inraper-ioneal adminisraion. Paiens should have a diag-nosis o sage III disease; opimal cyoreducion; ade-quae organ uncion; limied or no inra-abdominallesions; and be willing o olerae adverse even suchas inecion, abdominal pain, discomor, and caheercomplicaions. Neoadjuvan chemoherapy is defined as chemoher-apy ha is given beore primary surgical inervenion.

When a paien presens wih measaic ovarian cancerand/or is no a surgical candidae, neoadjuvan chemo-herapy is an alernaive o primary debulking surgery

wih he goal o decreasing umor size/volume and ul i-maely increasing he chance o maximal umor resec-ion when surgery becomes easible. In addiion, advan-ages o neoadjuvan chemoherapy include less preop-eraive morbidiy, less need or aggressive surgery, and asurvival rae similar o ha o paiens who underwenprimary debulking surgery.

Consolidation Terapy A he end o he primar y six cycles o chemoherapy,

all paiens are assessed or evidence o disease. Basedon he GOG 178 sudy ha evaluaed 3 versus 12 cycles


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o pacliaxel 135 mg/m2 over 3 hours once a monh aferpaiens achieved a complee response o primar y rea-men (surgery plus 6 cycles o pacliaxel and carbopla-in), he sandard consolidaion chemoherapy regimenis single-agen pacliaxel or 12 c ycles. Single-agen car-

boplain is also a reasonable opion or paiens wihplainum-sensiive disease who may have significan

residual neurooxiciy. However, is efficacy or consoli-daion has no been confirmed in randomized clinicalrials. A parial response o primary chemoherapy isdefined as a greaer han 50% decline in CA-125 (romhe presurgery concenraion) or umor regression. I isalso a reasonable opion o coninue wih single-agenpacliaxel or carboplain in paiens who have achieveda parial response o primar y reamen in an atemp oachieve a complee response. When he umor has no achieved a parial responseo primary reamen wih a axane/plainum regimen,alernaive chemoherapy agens should be considered

(see able 1-1).

reamen is coninued unil a com-plee response is achieved. I he paien has no or mini-mal disease afer compleion o primary chemoherapy,an accepable managemen approach is o observe hepaien every 3–4 monhs. Surveillance includes phys-ical examinaion, CA-125 concenraion (i a marker),and radiologic imaging as indicaed. During he obser-

vaion period, supporive care should be provided asindicaed unil he disease progresses and chemoher-apy is reiniiaed.

Chemotherapy for Recurrent Disease

Surgery and radiaion provide limied or no benefior recurren ovarian cancer. Chemoherapy is consid-ered he primary reamen opion or recurren ovariancancer. Plainum sensiiviy is a major prognosic acoror any chemoherapy in recurren ovarian cancer.

Several mechanisms can conribue o drug resis-ance in ovarian cancer, including increasing DNA repair,increasing drug inacivaion, he expression o onco-genes, and he level o p53 uncion. Mulidrug resisanceconinues o be a hurdle o overcome in he manage-men o cancer chemoherapy. When cancer recurs morehan 6 monhs afer he las plainum herapy, umorsare considered o have plainum-sensiive disease andmay respond o a second course o plainum-based rea-men wih response raes o 20% o 70%. Conversely, inpaiens wih plainum-resisan disease (relapse less han6 monhs afer plainum herapy), reamen opionsinclude agens wih an alernaive mechanism o acion(e.g., axanes, opoisomerase I inhibiors, anhracyclines,cyidine analogs, aromaase inhibiors, aniesrogens,lueinizing hormone–releasing hormone agoniss) orargeed agens discussed in he ollowing secion (seeable 1-1). Tese agens are usually given as single-agen,sequenial herapies.

Response raes are comparable or all he chemoher-apy agens currenly used in he reamen o recurrenovarian cancer. Tere are no guidelines ha speciy adefined sequence or number o cycles. Because responseraes are generally poor, a more viable opion is orpaiens wih plainum-resisan ovarian cancer o con-sider invesigaional rials. reamen decisions are based

on physician preerence; on paien acors such as age,comorbidiies, residual oxiciies, and hypersensiiviies;and on pas reamens.

Biological and argeted AgentsDuring he pas 5 years, clinical research has cen-

ered on he evaluaion and incorporaion o argeedagens such as he monoclonal anibodies (e.g., beva-cizumab, ceuximab) and he small-molecule yrosineinhibiors (e.g., suniinib, gefiinib, soraenib) or rea-men o all gynecologic malignancies. Te mos prog-ress has been demonsraed wih bevacizumab as boh asingle agen and in combinaion regimens or he rea-men o recurren ovarian cancer. Preliminary resuls owo mulicener phase III rials provide clinical daa osuppor he incorporaion o bevacizumab ino firs-lineand mainenance regimens o improve progression-reesurvival in ovarian cancer. Te impac on overall survivalis unknown. In addiion, muliple phase II sudies have

been conduced o evaluae he combinaion o bevaci-zumab wih oral cyclophosphamide, pacliaxel, and ohersecond-line agens (see able 1-1). Alhough iniial daasugges an improvemen in progression-ree survival

based on recen clinical experience in oher malignancies,i is oo early o deermine he impac o bevacizumab on

overall survival o paiens wih ovarian cancer.

PreventionTe use o oral conracepives reduces he risk o ovar-

ian cancer by abou 30%. Te risk coninues o decrease by abou 5% each year, oaling up o 50% wih 10 ormore years o use. Proecion coninues or 20 years aferdisconinuaion o he oral conracepive agen. In hegeneral populaion, oral conracepives are reasonable orecommend or he prevenion o sporadic (nonheredi-ary) ovarian cancer. However, risk versus benefi should

be considered or paiens wih a amily hisory o ovar-

ian and breas cancer because use o oral conracepiveshas been associaed wih an increased risk o breas can-cer. Alhough findings have no been confirmed in con-rolled rials, use o aspirin, ibuproen, and oher nonse-roidal ani-inflammaory drugs has been associaed wihan esimaed 47% risk reducion o ovarian cancer. Sev-eral in viro preclinical sudies sugges ha reinoids alsopreven ovarian cancer.

In women wih known amilial or geneic risk o devel-oping ovarian cancer, prophylacic surgery is an opionand is ofen considered afer compleion o childbear-ing. Prophylacic procedures include a bilaeral salpingo-


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oophorecomy and ubal ligaion wih or wihou hyser-ecomy. Beore surgery, paiens should undersand haprophylacic surgery is no absolue wih regard o riskreducion. For example, bilaeral salpingo-oophorecomyin paiens wih BRCA muaions reduced he cancer risk

by 80%; however, a residual risk o perioneal cancerremained in hese paiens wih an esimaed cumulaive

incidence o 4.3% a 20 years afer surgery. Alhough hemechanism o he prevenion/reducion o risk is no wellundersood, i may be caused by impaired ovarian unc-ion or decreased passage o inflammaory subsancesand inerrupion o rerograde ranspor o carcinogenshrough he allopian ube. Te repored reducion in riskis as grea as 30% or ubal ligaion and/or hyserecomyand persiss or 20–25 years afer he procedure.

Q P C

Chemotherapy

In recurren cancer, paiens ofen receive some ormo chemoherapy or an exended period or even or heduraion o heir lives. Preserving organ uncion and

bone marrow as well as minimizing cumulaive oxiciiesare imporan consideraions in adminisering chemo-herapy boh during primary reamen and in he man-agemen o paiens wih recurren disease. Many che-moherapy agens do no have specific dose modifica-ion guidelines or organ dysuncion; raher, he recom-mendaion is o use clinical judgmen, aking ino con-sideraion paien and reamen acors (able 1-2). Inpaiens wih recurren gynecologic cancer, especially

wih plainum-resisan disease, a conservaive approachshould be employed or dosing chemoherapy. ypically,dosage adjusmens are made or a creainine clearance

below 50 mL/minue and/or liver enzymes or bilirubinabove he normal limis.

Caveas specific o gynecologic oncology includeassessmen o kidney uncion and use o he appropriaemehod o esimaing creainine clearance. In 2008, heNaional idney Foundaion made recommendaions ouse he new isoope diluion mass specromery (IDMS)assay as he more accurae quanificaion o serum creai-nine o help wih earlier deecion o chronic kidney dis-

ease. However, he curren equaions or esimaing cre-ainine clearance (e.g., Cockcrof-Gaul, Jeliffe) have no

been adjused, sandardized, or validaed wih he IDMSserum creainine values. Use o he IDMS serum crea-inine in hese equaions ends o overesimae kidneyuncion. Tereore, he assay manuacurer should pro-

vide legacy sandards o he IDMS laboraory o developa specific equaion or conversion o he repored IDMS

value o he non-IDMS serum creainine or dosing alldrugs wih significan renal clearance, especially carbopl-ain. One such equaion is: non-IDMS serum creainine

value = (IDMS repored serum creainine value x 1.065)

+ 0.067. When he repored serum creainine value is lesshan 0.60 mg/dL (IDMS) or 0.8 mg/dL (non-IDMS),some cancer reamen ceners use an assigned serumcreainine value o 0.7–1 mg/dL in equaions or esima-ing creainine clearance.

Te oher variable or assessmen o kidney uncionor carboplain dosing is body weigh, which is relevan

when using he Cockcrof-Gaul equaion. In clinicalpracice, he adjusmen made or obesiy is highly vari-able. Ofen, when a paien’s acual body weigh is 20%o 30% above he ideal body weigh (or more recenlyor body mass index greaer han 30 kg/m2), an adjused

body weigh is used o esimae kidney uncion. Teappropriae use o he Cockcrof-Gaul equaion or heesimaion o kidney uncion or drug dosing remainsconroversial.

Table 1-2. Drugs Requiring Dosage Adjusmen in Presence o Organ Dysunciona

Kidney dysunction(in general, consider when CrCl is less han 50 mL/min)

Liver dysunction(in general, based on elevaions in bilirubin, AL, and/or AS)

Bleomycin Capeciabine

Capeciabine Doceaxel

Cisplain Doxorubicin

Cyclophosphamide Eoposide

Eoposide Gemciabine

Fluorouracil Liposomal doxorubicin

Gemciabine Pacliaxel

Iosamide Vincrisine

Liposomal doxorubicin Vinorelbine

opoecan

a When evaluaing he need or a dosage adjusmen or chemo herapy agens based on organ uncion oher acors needed o be consid-ered including: inenion o reamen; paien comorbidiies; perormance saus; oher organ uncion; complexiy o regimen (single

agen versus muliple agens); and risks associaed wih oxiciy (i.e., opions or managemen and impac on qualiy o lie). AL = ala nine aminoranserase ; A S = aspar ae am inoranserase ; CrCl =crea ini ne cleara nce.


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Supportive Careo preven hemaologic oxiciy, use o filgrasim is

an alernaive o dose reducions or increasing he rea-men inerval. Because o disease-relaed acors, emalesex, and cumulaive reamen, paiens wih gyneco-logic malignancies are suscepible o chemoherapy-induced nausea/vomiing. Consequenly, aniemeics

migh be needed wih regimens no ypically associaed wih emesis. Final ly, as disease progresses, paiens wihgynecologic malignancies, especially ovarian cancer,may have significan ascies. For agens dosed by bodysurace area or oal body weigh, he dry weigh or anesimaed adjused body weigh should be used or dos-age calculaions. Hypersensiiviy reacions are common in he rea-men o gynecologic cancers and have an incidencegreaer han 12% o 15% because o he use o axanesand plainum analogs. Pacliaxel is associaed wihinusion-relaed reacions ha can be atribued o hepolyehoxylaed casor oil diluen. Premedicaionsincluding a hisamine-1 or hisamine-2 blocker andcoricoseroids should be adminisered beore each doseo preven hypersensiiviy reacions. I a paien sill hasan inusion-relaed reacion, increasing he duraion ohe inusion or premedicaing wih coricoseroids henigh beore reamen will ofen preven sympoms. Ia paien develops a rue allergy, she should be desensi-ized as described in he ollowing. Plainum hypersensiiviy reacions are ofen delayedype I V hypersensiiviy reacions; hey can occur a anyime bu are more common afer seven or eigh lieimecycles o carboplain or cisplain. All paiens receiv-

ing a plainum agen should be insruced o reporany signs o a rash (one o he iniial signs o plainumhypersensiiviy) beween cycles. Plainum hypersensi-iviy reacions can be severe and are someimes aal.Cross-sensiiviy exiss beween carboplain and cis-plain. I a paien has a reacion o one plainum agen,desensiizaion is required o receive any uure plai-num agens. Plainum desensiizaion can be atemped

wih 24 hours o premedicaion including a hisamine-1or hisam ine-2 blocker and coricoseroids, ollowed byhe plainum agen given as a iraed inusion (1:1000,hen 1:100, hen 1:10, hen ull dose) over 4 hours. I

he paien experiences signs o hypersensiiviy a anyime during he iraed inusions or during he cycle beween doses, i is considered a desensiizaion ail-ure and alernaive chemoherapy or reamen opionsshould be considered.

Patient EducationUnil beter screening ools are available, paien edu-

caion remains he mos imporan inervenion orprevenion o gynecologic cancers. Women and healhcare providers need o be educaed on he early signsand sympoms o ovarian cancer. Tese signs include a

change in bowel or bladder habis, gasroinesinal dis-urbances, weigh gain, abdominal bloaing, and earlysaiey. Women should seek medical atenion i heyexperience hese sympoms or more han 6 weeks.

Ovarian cancer is ofen denoed he silen killer; women ofen ignore early signs and sympoms becausehey are so vague and ypically presen wih advanced

disease and a poor overall prognosis. Women shouldalso know heir amily medical hisory, specifically inregards o cancer, o deermine i addiional geneicscreening and prophylacic surgical inervenions areappropriae. Finally, wih he recen inroducion ohe HPV vaccines, women (and mohers) should bereminded ha hey only proec agains 2 o he 15 HPVsubypes associaed wih developmen o cervical can-cer. In addiion, rouine Pap smear screening is sil l rec-ommended in sexually acive young women despie vac-cinaion. Cervical cancer is prevenable by mainaininghealhy sexual liesyle choices as well as HPV vaccina-ion as appropriae. Young aduls should be educaed onprevenion o all sexually ransmited diseases, includ-ing HPV.

R P

Te pharmacis can assis he healh care eam in hemedical managemen o women wih gynecologic can-cer. Firs, all pharmaciss can provide paien educaionon opions or prevenion o gynecologic cancers, includ-ing use o he HPV vaccine, limiing he use o posmeno-pausal hormone herapy, and possible risk/benefis olong-erm oral conracepives use. Paien educaion can

be provided o paiens by pharmaciss o promoe earlydeecion o he gynecologic malignancies. Pharmacissalso have a key role in he prevenion and managemeno chemoherapy-induced oxiciies. oxiciy can be pre-

vened wih he proacive assessmen o organ uncionand recommending dosage adjusmens, appropriaeuse o granulocye-simulaing growh acors, and ani-emeic regimens. Pharmaciss can also conribue odevelopmen o supporive care plans needed o providecomor hroughou reamen. Tis is especia lly criical

when women are preparing or he end o lie.

CTere have been significan advancemens during he

pas 60 years in he managemen o gynecologic malig-nancies. Tese include he addiion o bevacizumab oreamen regimens or recurren disease, adopion oinraperioneal chemoherapy as firs-line reameno ovarian cancer, and inroducion o he HPV vac-cine or he prevenion o cervical cancer. Noneheless,major challenges remain in he managemen o gyne-cologic cancers. Paien educaion is essenial o assis

wih early diagnosis and o improve he poenial or


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achieving cure. Women mus be aware o he signs andsympoms o all he gynecologic cancers, especially he

vague sig ns and sympoms associaed wih ovarian can-cer. Unil beter reamen opions are made availableha resul in higher cure raes, a genler, more conserva-ive approach o paien care will help mainain qualiyo lie or paiens living wih gy necologic cancers.

A B

1. Lu H, Dinh M, ohlmann W, Wason P, Green J, Syn-gal S, e al . Gynecologic cancer as a “seninel cancer” or

women wih herediary nonpolyposis colorecal ca ncersyndrome. Obse Gynecol 2005;105:569–74.

Te auhors o his repor screened a large series o women wih HNPCC. Te resuls were firs presenedor prevenion o endomerial cancer, hen were laerdeveloped and validaed as predicive or prevenion ocolon cancer. Auhors screened five HNPCC regisr ieso obain inormaion on age a cancer diagnosis and

ype o cancer ha had developed (e.g., colon, endo-merial/ovarian). Daa were analyzed or associaions beween geneic acors and developmen o cancer.Te repor demonsraes he value and role o geneicscreening in prevenion o second cancers. Tis sudyhas been oundaional in ideniying women a highrisk o endomerial cancer and offering geneic coun-seling and/or geneic screening as appropriae o hemand exended amily members. Te sudy idenifieshe coninued obsacles o geneic screening includinginsurance issues, confidenialiy, and he need or beterscreening/monioring ools or paiens idenified o bea high risk based on geneic esing.

2. Sorbe B, Andersson H, Boman , Rosenberg P, all ingM. reamen o primary advanced and recurren endo-merial carcinoma wih a combinaion o carboplainand pacliaxel-long-erm ollow-up. In J Gynecol Can-cer 2008;18:803–8.

Alhoug h paclia xel and carboplain are he sandardo care or ovarian cancer, i has aken some ime or hisregimen o be used in he primary adjuvan reameno endomerial cancer. Tis is one o he iniial reporsha demonsraed a long-erm benefi or addiiono axanes o a plainum-based regimen or he rea-men o primary as well as recurren endomerial can-cer. A oal o 66 paiens wih endomerial cancer (18

primary and 48 recurren) were reaed wih six cycleso pacliaxel 175 mg/m2 over 3 hours plus carboplain(AUC = 5). Te overall response rae was 67%, wih 29%achieving a complee response and 38% achieving a par-ial response. Te sudy demonsraed an improvemenin progression-ree and overall survival, wih he 1-yearsurvival exceeding 80% and 3-year survival exceeding33%. Six cycles o pacliaxel and carboplain are nowcommonly adminisered afer compleion o primarysurgery and/or chemoherapy (cisplain) plus radiaion.Te addiion o chemoherapy o primary reamen oendomerial cancer has had significan improvemenin achieving and susaining complee response. Even

in recurren disease, reamen wih he combinaiono pacliaxel plus ca rboplain achieves beter responsescompared wih eiher agen alone.

3. eys HM, Robers JA, Bruneto VL, Zaino RJ, Spir-os NM, Bloss JD, e al. A phase III ria l o surgery wihor wihou adjuncive exernal pelvic radiaion her-apy in inermediae risk endomerial adenocarcinoma:

a Gynecologic Oncology Group sudy. Gynecol Oncol2004;92:744–51.

Radiaion is an acive reamen modaliy or endo-merial cancer; however, he long-erm benefi o radia-ion in combinaion wih surgery has been unclear. Tisphase III sudy randomized paiens wih newly diag-nosed endomerial cancer o receive whole pelvis radi-aion (5040 cGy) o be iniiaed 8 weeks afer surgerycompared wih no addiional reamen. Tis sudy d i-ereniaed paiens based on r isk o recurrence – eiherhigh inermediae risk or low inermediae risk basedon umor hisology, lymphovascular involvemen, ageolder han 50 years versus older han 70; his was consid-

ered imperaive o deermine he benefi o he addiiono adjuvan exernal radiaion afer surgery. A oal o392 women were enrolled and had 69 monhs o ollow-up. Radiaion reduced pelvic and vaginal recurrences by83% compared wih he no addiional reamen group.Overall survival improved rom 86% or paiens wihno addiional reamen o 92% in paiens who receivedradiaion, bu his was no saisically significan. Adju-

van radia ion is a common recommendaion in clini-cal pracice oday afer primary surgery or early sageendomerial cancer, especially or women a high iner-mediae risk; less benefi is observed in women wih alow risk. Considering he morbidiy and he impac o

poenial complicaions o whole abdominal radiaionon qualiy o lie, appropriae paien selecion or headdiion o radiaion o primary reamen is imporan.

4. Obel JC, Friberg G, Fleming GF. Chemoherapyin endomerial cancer. Clin Adv Hemaol Oncol2006;4:459–68.

In he pas 5 years, he role o chemoherapy orhe reamen o endomerial cancer has significanlyincreased. Tis clinical review describes he currenchemoherapy reamen opions or endomerial can-cer. Te number o paiens wih recurren endome-rial cancer is small, so only limied comparaive ran-

domized clinical rials are available or each chemo-herapy regimen. Hence, lieraure reviews such as hisone o common regimens in cli nical pracice are useulresources or reamen planning i n paiens wih recur-ren endomerial cancer. Tis review is a good overviewo he chemoherapy agens and combinaion regimenscommonly used in clinical pracice. Alhough random-ized clinical rials canno be used o predic responseraes, his inormaion is sill useul or curren clini-cal pracice and has poenial or developmen o newerregimens o be evaluaed in he uure. Te limiaionsand oxiciy o each agen and combinaion regimen aredescribed in deph.


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5. Brown J, Smih JA, Ramondeta LM, Sood A, RamirezP, Coleman RL, e al. Combinaion o gemciabineand cisplain is highly acive in women wih endome-rial carcinoma: resuls o a prospecive phase 2 rial.Cancer 2010;116:4973–9.

Tis phase I I sudy evaluaed he combinaion o gem-ciabine 1000 mg/m2 plus cisplain 35 mg/m2 adminis-ered on days 1 and 8 or reamen o plainum-sensi-ive and plainum-resisan endomerial cancer. A oalo 20 paiens were reaed in his single-insiuion,phase II sudy. A median o five cycles were received,

wih progression-ree survival o 7.5 monhs. Te objec-ive response rae was 50%, including wo compleeresponses in paiens wih plainum-resisan endome-rial cancer, eigh parial responses, and six paiens

wih sable disease, and only our paiens wih progres-sive disease. Tis sudy repors one o he more prom-ising clinical rial oucomes or endomerial cancer.Overall, gemciabine plus cisplain was well oleraed,

bu he use o filgras im was recommended by he inves-igaors o mainain dose inensiy and preven rea-

men delays ha were observed during he sudy sec-ondary o neuropenia. Tis regimen is also commonlyused in he reamen o recurren ovarian cancer.

6. Marniz S, ohler C, Muller M, Behrens , Hasenbein, Schneider A. Indicaions or primary and secondaryexeneraions in paiens wih cervical cancer. GynecolOncol 2006;103:1023–30.

Te exensive diagnosic and clinical evaluaionrequired o confirm paien eligibiliy or a compli-caed surgical exeneraion is described in his excel-len review. Exeneraions have considerable impacon a paien’s qualiy lie, bu wih appropriae paien

selecion i can be a curaive surgery or recurren cervi-cal and/or endomerial cancers. Tis review also differ-eniaes he indicaions or oal, anerior, and poseriorexeneraions. Because pharmaciss have l imied appre-ciaion o his complicaed surgical procedure, hispaper is a helpul resource o provide oundaion knowl-edge when working wih women who have a gyneco-logic cancer.

7. Villa LL, Cosa RL , Peta CA, Andrade RP, Paavo-nen J, Iverson OE, e al. High susained efficacy o pro-phylacic quadrivalen human papillomavirus ypes6/11/16/18 L1 virus-like paricle vaccine hrough 5

years o ollow-up. Br J Cancer 20 06;95:1459–66.

Tis is he 5-year ollow-up repor o he clinical effi-cacy o he quadrivalen HPV vaccine phase II random-ized, double blind, placebo conrolled licensing rial opreven HPV inecions and pre-invasive cervical can-cer lesions. A oal o 277 women aged 16–23 years wererandomized o he HPV 6/11/16/18 vaccine given a1, 2, and 6 monhs; hey were hen compared wih 275

women aged 16–23 years who received placebo a hesame ime inervals. Te primary end poin was inci-dence o inecion and/or cervical or exernal genialdisease. Sexual aciviy and HPV exposure were nodocumened during he sudy. Daa were analyzed on

he basis o he inen o rea regardless i he womancompleed sudy or no. Tis sudy should be reviewed

because i was one o he firs repors o a decline inHPV geomeric iers due o he use o a vaccine. Tissudy has since led o research o deermine i/whena booser o quadrivalen HPV vaccine is needed or irepeaing he vaccine series migh be indicaed. Despiehe decline in geomeric iers or HPV 18, he HPV

vaccine in he inen o rea group s il l had saisicallysignifican reducions in incidence o HPV inecionand pre-invasive cancer lesions.

8. Efiel PJ, Winer , Morris M, Levenback C, GrigsbyPW, Cooper J, e al. Pelvic irradiaion wih concurrenchemoherapy versus pelvic and para-aoric irradia-ion or high-risk cervical cancer: an updae o radiaionherapy oncology group rial (ROG) 90-01. J ClinOncol 200 4;22:872–80.

Tis landmark sudy by he Radiaion Terapy Oncol-ogy Group demonsraed ha adding chemoherapy oradiaion herapy improved he progression-ree and

overall survival o paiens wih cervical cancer. Tisrial was he firs randomized clinical sudy o demon-srae ha addiion o cisplain plus fluouracil chemo-herapy o he sandard radiaion regimen had a sais-ically sign ifican improvemen in he progression-reeand overall survival or women wih advanced sageIIB and II I cervical cancer. Te chemoherapy regimenincluded he combinaion o cisplain 75 mg/m2 wihfluorouracil 1000 mg/m2/day imes 4 days given dur-ing daily concurren radiaion reamens once every 3

weeks or oal o hree cycles. Tis sudy creaed a par-adigm shif in he reamen o cervical cancer: chemo-radiaion raher han radiaion a lone is given o paiens

wih advanced cerv ical cancer. However, because o

unaccepable oxiciy, fluorouracil has been dropped.

9. Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramon-deta LM, Boardman CH, e al. Phase III rial o ourcisplain-conaining double combinaions in sageIVB, recurren or persisen cervical carcinoma: aGynecologic Oncology Group Sudy. J Clin Oncol2009; 27:4649–55.

Hisorically, single-agen cisplain was he mainsayo reamen or recurren cervical cancer. Recenly,he use o cisplain-conaining doubles has evolvedin phase II and phase III rials in an effor o enhanceefficacy and overcome inheren drug resisance. Cis-

plain plus eiher pacliaxel, gemciabine, opoecan,or vinorelbine were compared in 513 women wih pri-mary sage IV or persisen/recurren cervical cancerin his phase III sudy (GOG 204). Te progression-ree and overall survival were equivalen. Te ulimaeconclusion rom his sudy was ha no superioriy wasobserved or vinorelbine, opoecan, or gemciabine incombinaion wih cisplain compared wih he sandardregimen o pacliaxel plus cisplain. In addiion, wihhe excepion o myelosuppression and alopecia, here

was no significan difference in oxici y beween heour regimens. Te cisplain plus gemciabine arm washe leas myelooxic, and he cisplain plus pacliaxel


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arm was predicably associaed wih he highes inci-dence o alopecia.

10. Abaid LN, Goldsein BH, Micha JP, Retenmaier MA,Brown JV 3rd, Markman M. Improved overall survival

wih 12 cycles o single-agen paclia xel mainenanceherapy ollowing a complee response o inducionchemoherapy in advanced ovarian carcinoma. Oncol-

ogy 2010;78:389–93.

Tis phase III sudy evaluaed he efficacy o con-solidaion chemoherapy wih 12 cycles o pacliaxel inpaiens wih advanced ovarian cancer who achieved acomplee response afer compleion o primary rea-men. Te sudy was sopped early afer he inerimanalysis ound a saisically significan improvemenin progression-ree survival compared wih he con-rol arm o consolidaion wih only hree cycles o pacli-axel. Afer his inerim repor, many women enrolledin he conrol arm chose o cross over o he 12 cycleso pacliaxel arm, making i difficul o deermine whaimpac, i any, exending reamen had on overall sur-

vival. Tis final repor on he 26 paiens, 13 in each armo he sudy, suggesed an improvemen in boh pro-gression-ree survival (12 monhs vs. 24 monhs) andoverall sur vival (38 vs. 80 monhs). Alhough he sudydid achieve saisical significance, larger confirmaorysudies are needed and are ongoing.

11. Garcia AA, Hire H, Fleming G, Yang D, sao-Wei DD,Roman L, e al. Phase II clinical rial o bevacizumaband low-dose meronomic oral cyclophosphamide inrecurren ovarian cancer: a rial o he Caliornia, Chi-cago, and Princess Margare Hospial phase II consor-ia. J Clin Oncol 2008;26:76–82.

Te use o argeed agens has become a predominanocus o drug developmen in oncology, and ovariancancer is no excepion. Tis phase II sudy in paiens

wih recurren ovarian cancer was one o he firs odemonsrae he benefi o he combinaion o bevaci-zumab 10 mg/kg once every 2 weeks and oral cyclo-phosphamide 50 mg once daily on progression-ree sur-

vival in recurren ovarian cancer. Te combinaion omeronomic, low-dose oral cyclophosphamide, definedas requen adminisraion o low-dose cyooxic che-moherapy given a requen inervals (daily in hissudy), and bevacizumab inravenously once every 2

weeks on a coninuous (28-day) regimen is commonlyused in clinical pracice oday. Te 70 paiens enrolledin his he sudy had a 6-monh progression-ree sur-

vival o 56% and a 24% parial response rae. Esimaedoverall survival was 16.9 monhs. Te combinaion is

well oleraed wih only limied oxici y (e.g., hyper-ension, aigue, pain). Te poenial or inesinal per-oraion has been he bigges concern in paiens wihovarian cancer. Appropriae paien selecion is impor-an. Te cos and reimbursemen or bevacizumab can

be a problem or many paien s, even hose wih i nsur-ance, bu pharmacy assisance programs are available oallow access o his beneficial regimen.

12. asumaa N, Yasuda M, akahash i F, Isonishi S, Jobo, Aoki D, e al. Dose-dense pacliaxel once a weekin combinaion wih carboplain every 3 weeks oradvanced ovarian cancer: a phase 3, open-label, ran-domised conrolled rial. Lance 2009;374:1331–8.

Tis phase I II sudy conduced in Japan generaed sig-nifican inernaional conroversy because he findingssuggesed a role or dose-dense chemoherapy. Hisori-cally, dose inensiy has no demonsraed any improve-men in progression-ree or overall survival in women

wih ovarian cancer; raher, his approach has signifi-canly increased oxiciy. Hence, here is hesiancy oadap dose densiy. Te resuls o his sudy are pro-

vocaive because he repored improvemen in mediansurv ival is 16 monhs in he sudy arm when compared

wih sandard herapy. An improvemen o his sig nifi-cance has no been noed since he 2006 inraperionealchemoherapy rial (see annoaed bibliography 13) or

he inroducion o pacliaxel use in he early 1990s. Addiional ollow-up is needed o deermine wheherhese robus resuls will be mainained. Some variaionsin he conrol chemoherapy arm occurred in his cli n-ical rial rom he sandard axane/plainum regimenused in Wesern counries. An ongoing sudy is evalu-aing his dose-dense axane/plainum regimen (pacli-axel 175 mg /m2 weekly plus carboplain AUC 5 every3 weeks) compared wih he sandard axane/plainumregimen (every 3 weeks) in women wih advanced ovar-ian cancer. Dose-dense regimens are sill consideredinvesigaional in he Unied Saes.

13. Armsrong D, Bundy B, Wenzel L, Huang HQ , Baer-gen R, Lele S, e al; Gynecologic Oncology Group.Inraperioneal cisplain and pacliaxel in ovarian can-cer. N Engl J Med 2006;354:34–43.

Alhough inraperioneal chemoherapy has been eval-uaed in gynecologic oncology or more han 30 years,his publicaion changed naional guidelines and manyclinical pracices. Tis was he firs sudy o inraperio-neal chemoherapy o demonsrae a saisically signifi-can improvemen in boh progression-ree and over-all survival. Tis regimen includes pacliaxel 135 mg/m2 inravenously over 24 hours on day 1 ollowed by cispla-in 100 mg/m2 inraperioneally on day 2, and pacliaxel60 mg/m2 inraperioneally on day 8. Te raionale andimporance o he day 8 pacliaxel has generaed signi-ican discussion because many paiens canno oleraeinraperioneal chemoherapy on day 8. Tis repor, as

well as many ollow-up repors rom his rial emphasizesha paien selecion is criical o achieve benefi andlimi oxiciy o inraperioneal herapy.


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Questions 1 and 2 pertain to the following case..P. is a 31-year-old woman who presens o your well-ness cener o discuss cancer prevenion. She is con-cerned abou her risk o developing cervical cancer.

1. Which one o the ollowing is the best interven-tion or screening and prevention o cervical can-cer or K.P.?

A. Papanicolaou (Pap) smear alone.B. Pap smear and human papillomavirus (HPV)

esing.C. Pap smear and HPV vaccine.D. Pap smear, HPV esing, and HPV vaccine.

2. .P. is also concerned abou her risk o developing

ovarian cancer. A grea-grandmoher on her aher’sside died o ovarian cancer a he age o 72. .P. hadher firs mensrual period a age 12. She currenlyakes no drug herapy or over-he-couner drugs.Her las pelvic examinaion, abou 1 year ago, wasnormal. She is in general good healh. Which one othe ollowing is the best intervention or K.P. toreduce her risk o developing ovarian cancer?

A. Inser an inrauerine progeserone device.B. Use oral conracepives or a leas 3 years.C. Seek geneic screening o evaluae or

herediary risk.

D. Monior cancer anigen (CA)-125concenraions annually.

3. A 72-year-old woman has begun o experience new-onse vaginal bleeding during he pas 3 monhs. Sheis nulliparous and had her firs mensrual period aage 10. She experienced menopause abou 15 yearsago, and she has been aking conjugaed esrogenand progeserone once daily coninuously since haime. She admis o ofen missing her progeseronedoses. Which one o the ollowing risk actorscontributed the most to her suspected endome-

trial cancer? A. Lack o a pregnancy.B. Use o hormone herapy.C. Nonadherence o progeserone.D. Her early menarche/lae menopause.

4. A 64-year-old woman presens o her primary careprovider wih a 7-week hisory o consipaion,aigue, bloaing, and early saiey. Te preliminarycompued omography (C) scan reveals a 5-cm x5-cm localized abdominal mass. Which one o the

ollowing is the best approach to confirm a diag-nosis in this patient?

A. C-guided biopsy.

B. Posiron emission omography.C. CA-125 plasma concenraion.D. Surgery wih saging.

5. A 24-year-old woman (weigh 76 kg, heigh 156cm) is newly diagnosed wih sage III cervical can-cer. Her laboraory values are hemoglobin 12 g/dL,plaele coun 156,000/mm3 , absolue neurophilcoun 2340/mm3 , bilir ubin 0.6 mg/dL, and serumcreainine 1.1 mg/dL by isoope diluion massspecromery (IDMS). Wh ich one o the ollow-ing is the best approach or primary treatment o

this patient’s newly diagnosed cervical cancer? A. Cisplain 40 mg/m2 weekly plus inernal/

exernal radiaion.B. Hyserecomy ollowed by adjuvan pacliaxel

and carboplain.C. opoecan plus cisplain ollowed by umor

reducive surgery.D. umor reducive surger y ollowed by

radioherapy.

6. An 82-year-old woman (creainine clearance, 41mL/minue), who has had no evidence o disease

or 13 monhs, is seen oday wih her firs recur-rence o ovarian cancer. Te oncologis saes hashe wans o rea he paien wih plainum-basedherapy. Which one o the ollowing is the bestregimen or the patient at this time?

A. Doxorubicin liposomal and carboplain.B. Doceaxel and carboplain.C. Gemciabine and carboplain.D. Gemciabine and cisplain.

Questions 7 and 8 pertain to the ollowing case.L.J. is a 37-year-old woman wih sage IIB recurrenovarian cancer. A her clinic appoinmen o be clearedor his monh’s cycle o chemoherapy, she learns shehas progressed on carboplain reamen. Her CA-125is 75 U/mL. Her complee blood coun is wihin normallimis, oal bilirubin is 0.8 mg/dL, alan ine aminorans-erase (AL) is 28 U/L, and creainine clearance is 35mL/minue.

7. Wh ich one o the ollowing is the best chemo-therapy regimen or L.J. to receive or her nextcourse o treatment?

S-A Q


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A. Liposomal doxorubicin.B. Gemciabine.C. opoecan.D. Doceaxel.

8. Tree monhs laer, L.J. undergoes repea C scans, which sugges progression o disease wih evidence

o new liver implans, carcinomaosis, and increas-ing size o abdominal umor. She also has new fluidaccumulaion in her perioneal caviy. Her labora-ory ess are CA-125 concenraion 356 U/mL,hemoglobin 9 g/dL, plaele coun 103,000/mm3 ,and absolue neurophil coun 1600/mm3. Whichone o the ollowing is the best next chemother-apy option or L.J.?

A. Cyclophosphamide and bevacizumab.B. opoecan and bevacizumab.C. Pacliaxel and bevacizumab.D. Bevacizumab alone.

9. A 47-year-old woman has jus compleed six cycleso pacliaxel and carboplain adjuvan reamen osage III opimally debulked ovarian cancer. She nowhas no evidence o disease, and her CA-125 concen-raion is 10 U/mL. Which one o the ollowing isthe best option to improve this patient’s overallsurvival?

A. Consolidaion chemoherapy wih pacliaxelonce a monh or 12 cycles.

B. Coninue pacliaxel and carboplain once every3 weeks or addiional hree cycles.

C. Monior wih C scan and CA-125concenraion every 3 monhs.

D. Second-look surgery ollowed by chemoherapyi posiive or residual disease.

Questions 10 and 11 pertain to the following case.E.D. is a 72-year-old woman wih recurren papillaryserous endomerial cancer. She had a hyserecomy ol-lowed by radiaion and hen six cycles o pacliaxel andcarboplain. She achieved a complee response o her pri-mary reamen and, or 2 years, has had no evidence odisease on surveillance. oday, she is old she has recur-

ren endomerial cancer.

10. Which one o the ollowing intravenous therapiesis the best second-line treatment or E.D.?

A. Pacliaxel and carboplain.B. Gemciabine and carboplain.C. Doxorubicin and carboplain.D. opoecan plus cisplain.

11. E.D.’s endomerial cancer progresses hrough hereamen ha was seleced above. Which one o the

ollowing intravenous therapies is the best treat-ment or E.D.’s recurrent endometrial cancer?

A. Cyclophosphamide and bevacizumab.B. Gemciabine and cisplain.C. Doxorubicin and opoecan.D. Iosamide plus vincrisine.

12. A 57-year-old woman has sage III recurren ovar-ian cancer. A her clinic appoinmen o be clearedo receive her chemoherapy, she learns she has pro-gressed on carboplain reamen. Her laboraoryess show: hemoglobin 11 g/dL, plaele coun123,000/mm3 , absolue neurophil coun 1600/mm3 , creainine clearance 75 mL/minue, oal bili-rubin 2.2 mg/dL, and AS 94 IU/L. Which one othe ollowing is the best chemotherapy regimenor this patient’s next course o treatment?

A. Liposomal doxorubicin.B. Gemciabine.C. opoecan.D. Doceaxel.

13. A proessional women’s neworking group has invied you o speak a heir Sepember monhly meeing orGynecologic Cancer Awareness monh. Te meeing

will ocus on endomerial cancer. Which one o theollowing prevention interventions is the mostimportant or reducing the risk o endometrialcancer?

A. Avoidance o hormone herapy.B. Paricipaion in weigh loss and exercise

programs.C. Paricipaion in universal geneic screening

programs.D. Undergoing prophylacic hyserecomy afer

childbearing years.

14. A 40-year-old woman has newly diagnosed advancedendomerial cancer. She is no a surgical candidae

because o her hisory o hear ailure and ype 2 diabees. Her creainine clearance is 95 mL/minue,oal bilirubin is 1.1 mg/dL, and AL is 18 U/L). Inaddition to cisplatin, which one o the ollowing

is the best regimen or this patient? A. Doxorubicin.B. Gemciabine.C. Pacliaxel.D. Doceaxel.

15. An obese 32-year-old woman had her firs mensrualperiod a age 9 bu has had irregular mensrual cyclessince age 15. She was recenly given a diagnosis opolycysic ovarian syndrome. An aun on her paer-nal side was given a diagnosis o ovarian cancer a he


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age o 67. Te paien asks you or her lieime risko developing ovarian cancer. Which one o the ol-lowing is the best screening option or ovariancancer in this patient?

A. Annual pelvic examinaion, ransvaginalulrasonography, and CA-125 concenraion.

B. Geneic screening.

C. Annual pelvic examinaion.D. CA-125 concenraion every 6 monhs.

16. A 34-year-old woman wih a hisory o sage IIb cervical cancer has jus compleed 5 weeks o exernalradiaion wih cisplain once weekly ollowed by

brachyherapy. She now has no evidence o disease.Te paien is he moher o hree children youngerhan 7 years. She would like aggressive reamen opreven cancer recurrence. Which one o the ol-lowing is the best plan afer completion o che-motherapy and radiation treatment?

A. Six cycles o opoecan plus cisplain.B. Six cycles o pacliaxel plus carboplain.C. Follow-up examinaions wih a Pap smear every

3 monhs.D. oal abdominal hyserecomy plus bilaeral

salpingo-oophorecomy.

17. A 63-year-old woman presens wih new-onse vag-inal bleeding or 1 monh. An endomerial biopsyconfirms a new cancerous lesion. She undergoesoal abdominal hyserecomy and bilaeral salpingo-oophorecomy wih opimal umor debulking sur-

gery and receives a diagnosis o sage IIIA, high-grade endomerial cancer. Which one o the ollow-ing is the best adjuvant approach or this patientto receive afer surgery?

A. Exernal beam radiaion alone.B. Follow-up examinaions every 3 monhs.C. Six cycles o pacliaxel plus carboplain.D. Exernal beam radiaion plus cisplain.

18. A 64-year-old woman received a diagnosis o sageIIIb cancer o he ovary. She compleed primaryreamen wih oal abdominal hyserecomy wih

bilaeral salpingo-oophorecomy and opimal deb-ulking surgery ollowed by six cycles o inravenouspacliaxel plus inraperioneal cisplain. She nowhas no evidence o disease on her C scan and herCA-125 concenraion is 8 U/mL (357 U/mL aime o diagnosis). Her gynecologic oncologis ellsher ha she has achieved a complee response o herprimary reamen. Which one o the ollowing isthe best next step to improve this patient’s pro-gression-ree and overall survival?

A. Pacliaxel 135 mg/m2 inravenously every 4 weeks or 12 cycles.

B. Second-look surgery wih perioneal washings.C. Bevacizumab 15 mg/kg every 21 days or 12

monhs.D. Follow-up examinaions every 3 monhs.


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