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Renal Cell Carcinoma: Nursing Considerations With the Use of Targeted Therapy

Nancy Moldawer, RN, MSN Clinical Research Operations Manager Division of Medical Oncology and Therapeutic Research City of Hope Duarte, California

Renal Cell Carcinoma (RCC)


Originates in the renal cortex Most common solid lesion occurring in the kidney (80-85% of all primary renal neoplasms)
Diseased Kidney

RCC Statistics
US estimates for 20071
51,190 individuals diagnosed with cancer of the kidney and renal pelvis 12,890 individuals died from cancer of the kidney and renal pelvis

3rd most common genitourinary cancer after prostate cancer and bladder cancer2 Median age at diagnosis: 65 years (2000-2004)1 Median age at death: 71 years (2000-2004)1

1. National Cancer Institute. SEER cancer statistics fact sheet: cancer of the kidney and renal pelvis. Accessed 2008. 2. Jemal A et al. CA Cancer J Clin. 2007;57:43.

RCC Statistics
An estimated 240,266 US individuals with a history of kidney and renal pelvis cancer were alive in 20041 5-year survival has improved2
50.9% 19751977 65.7% 19962003

1. National Cancer Institute. SEER cancer statistics fact sheet: cancer of the kidney and renal pelvis. Accessed 2008. 2. Ries LAG, et al. SEER Cancer Statistics Review. 2007;1975-2004.

US Yearly Kidney and Renal Pelvis Cancer Incidence and Mortality


15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 1975

Rate Per 100,000 Individuals

Incidence Mortality

1980

1985

1990

1995

2000

Year
Ries LAG et al. SEER Cancer Statistics Review, 1975-2004;2007.

Etiology of RCC
Environmental and clinical risk factors
Smoking1,2 Obesity1,3,4 Acquired cystic disease of the kidney (usually in association with dialysis)5,6 Analgesic abuse nephropathy7,8 Occupational exposure to toxic compounds9-11 Genetic predisposition12
1. Setiawan VW et al. Am J Epidemiol. 2007;166:932. 2. Hunt JD et al. Int J Cancer. 2005;114:101. 3. Pischon T et al. J Natl Cancer Inst. 2006;98:920. 4.Chow WH et al. N Engl J Med. 2000;343:1305. 5. Brennan JF et al. Br J Urol. 1991;67:342. 6. Truong LD et al. Am J Kidney Dis. 1995;26:1. 7. Chow WH et al. Int J Cancer. 1994;59:467. 8. Lornoy W et al. Lancet. 1986;1:1271. 9. Mandel JS et al. Cancer. 1995;61:601. 10. McLaughlin JK, Blot WJ. Int Arch Occup Environ Health. 1997;70:222. 11. Brauch H et al. Toxicol Lett. 2004;151:301. 12. Zbar B et al. J Urol. 2007;177:461.

Symptoms
Many patients with RCC are asymptomatic and have nonpalpable renal masses until late in natural disease course1,2

Common local symptoms


Hematuria Ipsilateral flank or abdominal pain Palpable mass

1. Lee CT et al. Urol Oncol. 2002;7:135. 2. Patard JJ et al. Eur Urol. 2003;44:226.

Symptoms
Common systemic symptoms Paraneoplastic disorders

Hypertension
Cachexia Weight loss Pyrexia

Neuromyopathy
Amyloidosis Elevated erythrocyte sedimentation rate Anemia

Abnormal liver function


Hypercalcemia Polycythemia Pain or mass related to metastatic disease

Physical Examination
Plays a limited role in diagnosing RCC May be valuable in situations where there is
A palpable abdominal mass A palpable cervical lymphadenopathy Non-reducing varicocele Bilateral lower extremity edema suggestive of venous involvement

Any of the above findings warrants radiologic examination


Ljungberg B et al. Eur Urol. 2007;51:1502.

Extent of Disease at Diagnosis


Most renal cancers diagnosed when disease still localized to primary site
Unknown 5%

Metastatic Spread 20%

Locoregional Spread 19%

Localized Disease 56%

National Cancer Institute. SEER cancer statistics fact sheet: cancer of the kidney and renal pelvis. Accessed 2008.

Stages of RCC
Stage I: Cancer is in the kidney only and size of the tumor is 7.0 cm in diameter Stage II: Cancer is in the kidney only, but size of the tumor is >7.0 cm in diameter

Stage III: Tumor in the kidney may be any size, but extends beyond layer of tissue (Gerotas fascia) that encapsulates kidney and adrenal gland. Cancer may have spread to blood vessels that carry blood away from kidney.

Stage IV: Tumor in the kidney extends beyond Gerotas fascia and/or cancer has spread to one or more lymph nodes near kidney. Cancer may have spread to other organs such as lungs, liver, brain, or bones.

Oregon Health & Science University. Kidney Cancer Program. Available at: http://www.ohsu.edu/health/page.cfm?id=13584

RCC Subtypes1,2
Subtype
Clear cell carcinoma

Prevalence
7585%

Tumor Features
Multinodular; yellow cut surface with gray & white foci Ball-shaped outline, dotted pattern; beige, white, or greasy brown 1 solid tumor nodule with slightly lobulated surface; orange cut surface Typically solitary, slightly lobulated; tan-brown cut surface Large; cut surface firm, white, interspersed with necroses

Microscopic Features

Chromophilic (papillary) carcinomas Chromophobic carcinomas Oncocytomas

1015%

510%

Uncommon (2%) Very rare

Collecting duct tumors (a.k.a. Bellinis duct)

1. Thoenes W et al. Path Res Pract. 1986;181:125. 2. Strkel S, van den Berg E. World J Urol. 1995;13:153.

Prognostic Clinical Factors


Several clinical factors associated with poor survival in patients with RCC
Poor performance status1,2 Presence of RCC symptoms and/or paraneoplastic syndrome1-6
Anemia, hypercalcemia, hepatopathy, thrombocytosis, fever, weight loss

Obesity7
1. Zisman A et al. J Clin Oncol. 2001;19:1649. 2. Motzer RJ et al. J Clin Oncol. 1999;17:2530. 3. Suppiah R et al. Cancer. 2006;107:1793. 4. Bensalah K et al. J Urol 2006;175:859. 5. Fahn HJ et al. J Urol. 1991;145:248. 6. Patard JJ et al. J Urol. 2004;172:2167. 7. Calle EE et al. N Engl J Med. 2003;348:1625.

Recurrent/Metastatic RCC Prognosis


Patients with recurrent or metastatic RCC have very poor prognosis
Factors Associated With Survival Outcomes1-4
Longer Survival Long interval between nephrectomy & development of distant metastases Single site of metastatic disease Absence of retroperitoneal adenopathy Right involved kidney Shorter Survival Karnofsky performance status <80% Lactose dehydrogenase >1.5 x ULN Corrected serum calcium >10 g/dL Hemoglobin <LLN Absence of nephrectomy (ie, no disease-free interval) Prior radiotherapy

1. Motzer RJ et al. J Clin Oncol. 1999;17:2530. 2. Mekhail TM et al. J Clin Oncol. 2005;23:832. 3. Choueiri TK et al. Ann Oncol. 2007;18:249. 4. Han KR et al. Urology. 2003;61:314.

Advanced RCC
Treatment options other than surgery
Radiotherapy

Not an effective option


Chemotherapy
Not an effective option

Immunotherapy
Limited/some benefit

Targeted therapy
Clinical benefit; active area of research and further refinement
1. National Cancer Institute. SEER cancer statistics fact sheet: cancer of the kidney and renal pelvis. Accessed 2008. 2. Janzen N et al. Urol Clin North Am. 2003;30:843.

Angiogenesis
Angiogenesis is a key determinant in pathophysiology of RCC1 RCCs are most vascularized of all solid tumors2
Map of Blood Flow to a Metastatic RCC Lesion

1. Izawa JI, Dinney CP. CMAJ. 2001;164:662. 2. Cristofanilli M et al. Nat Rev Drug Discov. 2002;1:415.

Role of VEGF in Angiogenesis

Cristofanilli M et al. Nat Rev Drug Discov. 2002;1:415.

Growth Factors
Vascular endothelial growth factor (VEGF) key growth factor involved in angiogenesis1,2
VEGF mRNA expression correlates with vascularization

VEGF is overexpressed in most clear-cell RCCs

Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) play role in angiogenesis and oncogenesis

1. Cristofanilli M et al. Nat Rev Drug Discov. 2002;1:415. 2. De Mulder PH. Ann Oncol. 2007;18:ix98.

Targeting the Molecular Pathways of RCC Oncogenesis


Endothelial/ Tumor cells PDGF

Upregulation in response to HIF-1 transcription

bevacizumab

sorafenib, sunitinib

VEGF

EGF
gefitinib, cetuximab, erlotinib, panitumumab

Ras sorafenib RAF PI3K Gene expression

MEK

AKT rapamycin, temsirolimus, everolimus

ERK Angiogenesis/Cell proliferation/Cell survival

mTOR

Stadler WM. Cancer. 2005;104:2323.

Clinically Available Targeted Agents for Advanced RCC


4 targeted agents available for advanced RCC
Agent Target Efficacy in Randomized Phase III Trials

Comparison
Bevacizumab VEGF Bevacizumab + IFN- vs Placebo + IFN-1 Bevacizumab + IFN- vs IFN-2 Sunitinib Sorafenib VEGF receptor VEGF receptor mTOR Sunitinib vs IFN-3 Sorafenib vs Placebo4 Temsirolimus vs IFN- vs both agents5

No. Treated
649 732 750 903

ORR
31% vs 13% 26% vs 13% 37% vs 9% 10% vs 2%

TTP (mos)
10.2 vs 5.4; P=.0001 8.5 vs 5.2; P<.0001 11.1 vs 5; P=.00001 5.5 vs 2.8; P=.000001 3.7 vs 1.9 (IFN-); P=.001

Temsirolimus

626

11% vs 7% vs 8%

ORR=overall response rate; TTP=time to progression

1. Escudier B et al. Lancet. 2007;370:2103. 2. Rini BI et al. 2008 ASCO Genitourinary Cancers Symposium. Abstract 350. 3. Motzer RJ et al. N Engl J Med. 2007;356:115. 4. Escudier B et al. N Engl J Med. 2007;356:125. 5. Hudes G et al. N EngJ Med. 2007;356:2271.

Integrating the Oncology Nurse Into the New Paradigm of Targeted Therapy
The new therapeutic paradigm of moleculartargeted therapy presents new challenges for oncology nurses
Induces tumor stabilization vs complete responses Controls disease vs curing disease Unique side-effect profiles As the landscape of RCC treatment continues to evolve, the nurse remains on the forefront of drug discovery, administration, and adverse event monitoring
Moldawer N, Wood LS. Kidney Cancer J. 2006;4:25-32.

Sunitinib
An orally administered tyrosine kinase inhibitor

Approved for treatment of advanced RCC in January 2006


Potent inhibitor of VEGFR, PDGFR, and FLT-31 Has demonstrated efficacy in clear-cell RCC as second-line therapy after IL-23 and as first-line therapy compared with interferon2

1. Abrams TJ, et al. Mol Cancer Ther. 2003;2:471-478. 2. Motzer RJ. JAMA. 2006;295:2516-2524.

Sunitinib: Dosing and Administration


50 mg QD 4 weeks on 2 weeks off1

May be taken with or without food Sunitinib and its active metabolite metabolized primarily by CYP3A4

Requires dose adjustment when administered with CYP3A4 inhibitors or inducers2


Important to assess any concomitant medications patient is taking

1.Faivre S, et al. J Clin Oncol. 2006;24:25-35. 2. Hiles JJ, Kolesar JM. Am J Health-Syst Pharm. 2008;65:123-131.

Sunitinib: Most Common Adverse Events (20%)


Adverse Event
Fatigue Diarrhea Nausea Altered taste Mucositis/stomatitis Anorexia Hypertension Bleeding Vomiting Dyspepsia Rash Abdominal pain Hand-foot syndrome

All Grades (%)


58 58 49 44 43 38 30 30 28 28 27 22 21

Sutent (sunitinib) Full Prescribing Information. Pfizer Inc. October 2007.

Sorafenib
An orally administered multikinase inhibitor

Approved for treatment of advanced RCC in December 2005


Inhibits VEGFR 1, 2, and 3, PDGFR, FLT-3, c-Kit, and RET kinases1,2 Has demonstrated efficacy as second-line monotherapy in metastatic RCC3,4
1.Bhojani N, et al. Eur Urol. 2008;53:917-930. 2. Wilhelm SM, et al. Cancer Res. 2004;64:7099-7109. 3. Ratain MJ, et al. J Clin Oncol. 2006;24:2505-2512. 4. Escudier B et al. N Engl J Med. 2007;356:125.

Sorafenib: Dosing and Administration


Formulated as a 200-mg tablet

Daily dosing of 400 mg BID


If dose reduction is required, dose may be reduced to:
400 mg QD, and subsequently to 400 mg QOD

Primarily metabolized by CYP3A4 and undergoes glucuronidation

Moldawer N, Wood LS. Kidney Cancer J. 2006;4:25-32.

Sorafenib: Most Common Adverse Events (20%)


Adverse Event
Diarrhea Fatigue Abdominal pain Weight loss Anorexia Nausea Hand-foot reaction

All Grades (%)


55 46 31 30 29 24 21

Nexavar (sorafenib) Full Prescribing Information. Bayer HealthCare. 2008.

Sunitinib and Sorafenib Adverse Events: Nursing Implications1,2


Diarrhea
Treat initially with diet modification (low residue) and loperamide
If loperamide insufficient, give diphenoxylate HCl with atropine Additional options include tincture of opium, Culturelle (oral probiotic), and Dannon yogurt containing bifidobacterium

Fatigue
Adjust activities to allow for rest periods and maximize fluid and caloric intake

1. Wood LS. Oncology Nurs News. 2007;3:19-20. 2. Wood LS. Oncology Nurs News. 2007;4:37-38.

Sunitinib and Sorafenib Adverse Events: Nursing Implications1,2 (cont.)


Functional or clinical mucositis
Dietary modifications
Avoidance of carbonated beverages and spicy foods Eating foods at room temperature Medications Topical lidocaine or Xylocaine BMX Solution (Benadryl/Mylanta, Xylocaine)

Rincinol (OTC topical solution containing aloe vera)


Nystatin suspension or clotrimazole troches for clinical mucositis
1. Wood LS. Oncology Nurs News. 2007;3:19-20. 2. Wood LS. Oncology Nurs News. 2007;4:37-38.

Sunitinib and Sorafenib Adverse Events: Nursing Implications1,2 (cont.)


Taste changes and anorexia
Maximize caloric intake Encourage 6 small meals per day Use of flavorings and gravy to enhance food taste

Hand-foot reaction Liberal use of emollients Avoid activities that cause pressure, abrasion, or irritation to hands and feet Application of Udderly Smooth lotion BID Other options include: Bag Balm Aveeno Skin Relief Moisturizing Cream Aveeno Intense Relief Foot Cream Kerasal ointment Keralec cream Zims Crack Crme Biafine Topical Emulsion
1. Wood LS. Oncology Nurs News. 2007;3:19-20. 2. Wood LS. Oncology Nurs News. 2007;4:37-38.

Bevacizumab
Monoclonal antibody to VEGF active in multiple tumor types First biological antiangiogenic agent approved by US FDA

Approved for use in colorectal, non-small cell lung, and metastatic breast cancers1
Phase 3 studies are evaluating bevacizumab in a variety of solid tumor types2
1. Avastin (bevacizumab) Full Prescribing Information. Genentech, Inc. March 2008. 2. National Cancer Institute website. http://www.cancer.gov/clinicaltrials/search.

Bevacizumab: Dosing and Administration


Usual dosage of bevacizumab for treatment of colorectal cancer is 5 mg/kg IV every 2 weeks Dosage in investigational trials of RCC has generally been 10 mg/kg IV every 2 weeks1,2

Can be associated with hypersensitivity reactions

1. Hainsworth JD, et al. J Clin Oncol. 2005;23:7889-7996. 2. Bukowski RM, et al. J Clin Oncol. 2007;25:4536-4541.

Bevacizumab: Serious Adverse Events (10%)


Adverse Event Bevacizumab 10 mg/kg (N=39)
Bevacizumab 3 mg/kg (N=37)

%
Epistaxis 21

%
14

Hypertension
Fever without infection

36 (21)a
10

3
3

Malaise Hematuria Hyponatremia Proteinuriab Elevated ALT Chest pain


aPercent b1+

33 13 8 64 (8)a 10 5 (5)a

16 3 11 41 (5)a 5 0

of patients with grade 3 toxic effects or 150 mg/24 hrs Grade 3 hypertension was defined as hypertension not completely controlled by one standard medication Grade 3 proteinuria was defined as urinary excretion of >3.5 g of protein per 24 hrs Yang CH, et al. N Engl J Med. 2003;349:427-434.

Bevacizumab Adverse Events: Nursing Implications


Bleeding
Obtain patient history of unusual bleeding or clotting, GI perforation, and use of anticoagulants Avoid anticoagulant therapy if possible, especially concomitant use of bevacizumab with warfarin and 5-FU

Educate patient about signs of bleeding (ie, epistaxis, bleeding gums during tooth brushing, red or black, tarry stools, vomiting blood)

Thrombosis
Educate patient about signs of thrombosis that include
Sudden chest pain Difficulty breathing
Ignoffo RJ. Am J Health-Syst Pharm. 2004;61(Suppl 5):21-26.

Bevacizumab Adverse Events: Nursing Implications (cont.)


Hypertension
Establish baseline blood pressure (BP) and monitor weekly during therapy Ensure that patient has a BP monitor at home Continue antiphypertensive therapy in patients already taking it when bevacizumab is initiated Consult MD to initiate mild antihypertensive if patient develops hypertension during bevacizumab therapy Consider using ACE inhibitor and avoid antihypertensive agents that inhibit CYP3A4 (eg, verapamil, diltiazem)

Proteinuria
Monthly monitoring of renal function and serum protein concentration
Ignoffo RJ. Am J Health-Syst Pharm. 2004;61(Suppl 5):21-26.

Temsirolimus
An inhibitor of mammalian target of rapamycin (mTOR) kinase, a component of intracellular signaling pathways1 Binds to an abundant intracellular protein FKBP12, forming a complex that inhibits mTOR2,3 First mTOR inhibitor approved for treatment of advanced RCC

Approved by FDA on May 30, 2007


1. Schmelzle T, Hall MN. Cell. 2000;103:253-262. 2. Skotnicki JS, et al. Clin Cancer Res. 2001;7(Suppl):3749-3750. 3. Harding MW. Clin Cancer Res. 2003;9:2882-2886.

Temsirolimus: Dosing and Administration


Approved dose for advanced RCC is 25 mg IV weekly over a 30- to 60-minute period Patients should receive prophylactic diphenhydramine 2550 mg IV prior to the start of each dose If patient develops a hypersensitivity reaction during infusion:
Stop infusion Observe patient at least 3060 minutes Notify MD Treatment may be resumed at discretion of MD with administration of an H1-receptor antagonist (eg, diphenhydramine), if not previously administered, and/or an H2-receptor antagonist (eg, famotidine 20 mg IV or ranitidine 50 mg IV) 30 minutes before restarting temsirolimus Extend infusion time to 60 minutes
Torisel (temsirolimus) Full Prescribing Information. Wyeth Pharmaceuticals. May 2007.

Temsirolimus: Most Common Adverse Events (30%)


Adverse Event
Asthenia Rash Mucositis Nausea Edema Anorexia

All Grades (%)


51 47 41 37 35 32

Torisel (temsirolimus) Full Prescribing Information. Wyeth Pharmaceuticals. May 2007.

Temsirolimus Adverse Events: Nursing Implications


Rash
Observe for acne-like rash Consider antihistamines for itching Counsel patient to use skin emollients, avoid agents that cause skin drying effects, and avoid sun exposure

Anemia
Monitor hemoglobin and hematocrit regularly during therapy

Anorexia
Maximize caloric intake

Temsirolimus Adverse Events: Nursing Implications (cont.)


Hyperlipidemia
Monitor serum cholesterol and triglycerides prior to and during therapy

Hyperglycemia
Monitor serum glucose prior to and periodically during therapy

Infection
Monitor for sore throat, appearance of sputum, urine, and stool Monitor vital signs regularly Educate patient about recognizing signs of infection

Temsirolimus Adverse Events: Nursing Implications (cont.)


Interaction with CYP3A4 inhibitors
Avoid concomitant use of temsirolimus with:
Grapefruit juice Ketoconazole Itraconazole Clarithromycin Atazanavir Indinavir Nefazodone Nelfinavir Ritonavir Saquinavir Telithromycin Vorizonazole
Torisel (temsirolimus) Full Prescribing Information. Wyeth Pharmaceuticals. May 2007.

Temsirolimus Adverse Events: Nursing Implications (cont.)


Interaction with CYP3A4 inducers
Avoid concomitant use of temsirolimus with:
Dexamethasone Phenytoin Carbamazepine Phenobarbital Rifampin Rifabutin

Torisel (temsirolimus) Full Prescribing Information. Wyeth Pharmaceuticals. May 2007.

NCCN Guidelines: Explanation of Categories of Evidence


Category 1
Recommendation based on high-level evidence (ie, high-powered randomized clinical trials or meta-analyses) NCCN Guidelines Panel has reached uniform consensus that the recommendation is indicated

Category 2A
Recommendation based on lower-level evidence Lower-level evidence is interpreted broadly and may range from phase 2 to large cohort studies to case studies In many instances, retrospective studies derived from clinical experience of treating large numbers of patients and Guidelines Panel members have first-hand knowledge of data

National Comprehensive Cancer Network. Available at: http://www.nccn.org.

NCCN Guidelines: Explanation of Categories of Evidence


Category 2B
Recommendation based on lower-level evidence There is nonuniform consensus that the recommendation should be made In these instances, institutions take different approaches to the management of a particular clinical scenario

Category 3
Including the recommendation has engendered a major disagreement among NCCN Guidelines Panel members Level of evidence not pertinent in this category because experts can disagree about the significance of high-level trials

National Comprehensive Cancer Network. Available at: http://www.nccn.org.

NCCN Practice Guidelines in Oncology: Kidney Cancer


FIRST-LINE THERAPY
Predominant clear cell histology Relapse or Stage IV and medically or surgically unresectable Clinical trial or Sunitinib (category 1) or Temsirolimus for poor-prognosis patientsa (category 1) or Bevacizumab + IFN or High-dose IL-2 for selected patients or Sorafenib for selected patients and Best supportive careb
NCCN Clinical Practice Guidelines in Oncology. 2007;v. 1. 2008.

aTemsirolimus

indicated for poor-prognosis patients, defined as those with 3 predictors of short survival bBest supportive care can include palliative RT, metastasectomy or biphosphonates for bony metastasis

NCCN Practice Guidelines in Oncology: Kidney Cancer


FIRST-LINE THERAPY (cont.)
Clinical trial (preferred) or Temsirolimusa (category 1 for poor-prognosis, category 2A for other risk groups) or Sorafenib or Sunitinib or Chemotherapy (category 3): Gemcitabine or capecitabine or floxuridine or 5-FU or doxorubicin (in sarcomatoid only) and Best supportive careb

Relapse or Stage IV and medically or surgically unresectable

Non clear cell histology

aTemsirolimus indicated for poor-prognosis patients, defined as those with 3 predictors of short survival bBest supportive care can include palliative RT, metastasectomy or biphosphonates for bony metastasis NCCN Clinical Practice Guidelines in Oncology. 2007;v. 1. 2008.

NCCN Practice Guidelines in Oncology: Kidney Cancer


SUBSEQUENT THERAPY
Clinical trial (preferred) or Sorafenib (category 1 following cytokine therapy and category 2A following TKI) or Sunitinib (category 1 following cytokine therapy and category 2A following TKI) or Temsirolimus (category 2A following cytokine therapy and category 2B following TKI) or IFN (category 2B) or High dose IL-2 (category 2B) or Low dose IL-2 + IFN (category 2B) or Bevacizumab and Best supportive carea
NCCN Clinical Practice Guidelines in Oncology. 2007;v. 1. 2008.

Progression

aBest

supportive care can include palliative RT, metastasectomy or biphosphonates for bony metastasis

Targeted Therapies: Patient Education and Management


Assess patient at initiation of therapy

Establish treatment schedule and regularly scheduled visits with healthcare provider
Ensure that patient sees an MD or RN at the beginning of each treatment cycle

Provide both written and verbal instructions about RCC treatment and side effect management
Patient should be instructed to contact healthcare provider immediately when experiencing any side effects Document therapy and response to treatment on appropriate medication flow sheets and nursing notes
Moore SH. Online educational activity 2006.

Summary
3 targeted therapies are currently FDA-approved for treatment of advanced RCC Targeted therapies have manageable side effects with appropriate nursing interventions Patients have prolonged survival with control of their cancer

Identified prognostic factors correlate with prognosis and treatment decisions (NCCN guidelines)

Future Considerations
Do these targeted therapies have a role in the adjuvant setting? Do combinations of these targeted therapies offer better clinical results or cause increased toxicity?

Patient preference: oral or IV therapy?

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