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

1
Renal Cell CarcinomaNursing 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

2
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
3
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. 20075743.
4
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 1975?1977
• 65.7 1996?2003

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. 20071975-2004.
5
US Yearly Kidney and Renal Pelvis Cancer
Incidence and Mortality

• Ries LAG et al. SEER Cancer Statistics Review,
  1975-20042007.

6
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.
2007166932. 2. Hunt JD et al. Int J Cancer.
2005114101. 3. Pischon T et al. J Natl Cancer
Inst. 200698920. 4.Chow WH et al. N Engl J Med.
20003431305. 5. Brennan JF et al. Br J Urol.
199167342. 6. Truong LD et al. Am J Kidney Dis.
1995261. 7. Chow WH et al. Int J Cancer.
199459467. 8. Lornoy W et al. Lancet.
198611271. 9. Mandel JS et al. Cancer.
199561601. 10. McLaughlin JK, Blot WJ. Int
Arch Occup Environ Health. 199770222. 11.
Brauch H et al. Toxicol Lett. 2004151301. 12.
Zbar B et al. J Urol. 2007177461.
7
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. 20027135. 2.
Patard JJ et al. Eur Urol. 200344226.
8
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

9
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. 2007511502.
10
Extent of Disease at Diagnosis

• Most renal cancers diagnosed when disease still
  localized to primary site

National Cancer Institute. SEER cancer statistics
fact sheet cancer of the kidney and renal
pelvis. Accessed 2008.
11
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 gt7.0 cm in diameter
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.
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.
Oregon Health Science University. Kidney Cancer
Program. Available at http//www.ohsu.edu/health/
page.cfm?id13584
12
RCC Subtypes1,2
Subtype Prevalence Prevalence Tumor Features Microscopic Features
Clear cell carcinoma 7585 Multinodular yellow cut surface with gray white foci Multinodular yellow cut surface with gray white foci
Chromophilic (papillary) carcinomas 1015 Ball-shaped outline, dotted pattern beige, white, or greasy brown Ball-shaped outline, dotted pattern beige, white, or greasy brown
Chromophobic carcinomas 510 1 solid tumor nodule with slightly lobulated surface orange cut surface 1 solid tumor nodule with slightly lobulated surface orange cut surface
Oncocytomas Uncommon (2) Typically solitary, slightly lobulated tan-brown cut surface Typically solitary, slightly lobulated tan-brown cut surface
Collecting duct tumors (a.k.a. Bellinis duct) Very rare Large cut surface firm, white, interspersed with necroses Large cut surface firm, white, interspersed with necroses
1. Thoenes W et al. Path Res Pract. 1986181125.
2. Störkel S, van den Berg E. World J Urol.
199513153.
13
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. 2001191649.
2. Motzer RJ et al. J Clin Oncol. 1999172530.
3. Suppiah R et al. Cancer. 20061071793. 4.
Bensalah K et al. J Urol 2006175859. 5. Fahn
HJ et al. J Urol. 1991145248. 6. Patard JJ et
al. J Urol. 20041722167. 7. Calle EE et al. N
Engl J Med. 20033481625.
14
Recurrent/Metastatic RCC Prognosis

• Patients with recurrent or metastatic RCC have
  very poor prognosis

Factors Associated With Survival Outcomes1-4
Longer Survival Shorter Survival
Long interval between nephrectomy development of distant metastases Single site of metastatic disease Absence of retroperitoneal adenopathy Right involved kidney Karnofsky performance status lt80 Lactose dehydrogenase gt1.5 x ULN Corrected serum calcium gt10 g/dL Hemoglobin ltLLN Absence of nephrectomy (ie, no disease-free interval) Prior radiotherapy
1. Motzer RJ et al. J Clin Oncol. 1999172530.
2. Mekhail TM et al. J Clin Oncol. 200523832.
3. Choueiri TK et al. Ann Oncol. 200718249. 4.
Han KR et al. Urology. 200361314.
15
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. 200330843.
16
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. 2001164662. 2.
Cristofanilli M et al. Nat Rev Drug Discov.
20021415.
17
Role of VEGF in Angiogenesis
Cristofanilli M et al. Nat Rev Drug Discov.
20021415.
18
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.
20021415. 2. De Mulder PH. Ann Oncol.
200718ix98.
19
Targeting the Molecular Pathways of RCC
Oncogenesis
Upregulation in response to HIF-1 transcription
bevacizumab
sorafenib, sunitinib
Endothelial/Tumor cells
gefitinib, cetuximab, erlotinib, panitumumab
sorafenib
Gene expression
rapamycin, temsirolimus, everolimus
Angiogenesis/Cell proliferation/Cell survival
Stadler WM. Cancer. 20051042323.
20
Clinically Available Targeted Agents for
Advanced RCC

• 4 targeted agents available for advanced RCC

Agent Target Target Efficacy in Randomized Phase III Trials Efficacy in Randomized Phase III Trials Efficacy in Randomized Phase III Trials Efficacy in Randomized Phase III Trials
Agent Target Target Comparison No. Treated ORR TTP (mos)
Bevacizumab VEGF Bevacizumab IFN-? vs Placebo IFN-?1 Bevacizumab IFN-? vs Placebo IFN-?1 649 31 vs 13 10.2 vs 5.4 P.0001
Bevacizumab IFN-? vs IFN-?2 Bevacizumab IFN-? vs IFN-?2 732 26 vs 13 8.5 vs 5.2 Plt.0001
Sunitinib VEGF receptor Sunitinib vs IFN-?3 Sunitinib vs IFN-?3 750 37 vs 9 11.1 vs 5 P.00001
Sorafenib VEGF receptor Sorafenib vs Placebo4 Sorafenib vs Placebo4 903 10 vs 2 5.5 vs 2.8 P.000001
Temsirolimus mTOR Temsirolimus vs IFN-? vs both agents5 Temsirolimus vs IFN-? vs both agents5 626 11 vs 7 vs 8 3.7 vs 1.9 (IFN-?) P.001
1. Escudier B et al. Lancet. 20073702103. 2.
Rini BI et al. 2008 ASCO Genitourinary Cancers
Symposium. Abstract 350. 3. Motzer RJ et al. N
Engl J Med. 2007356115. 4. Escudier B et al. N
Engl J Med. 2007356125. 5. Hudes G et al. N
EngJ Med. 20073562271.
ORRoverall response rate TTPtime to progression
21
Integrating the Oncology Nurse Into the New
Paradigm of Targeted Therapy

• The new therapeutic paradigm of
  molecular-targeted 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.
2006425-32.
22
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.
20032471-478. 2. Motzer RJ. JAMA.
20062952516-2524.
23
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. 20062425-35.
2. Hiles JJ, Kolesar JM. Am J Health-Syst Pharm.
200865123-131.
24
SunitinibMost Common Adverse Events (20)
Adverse Event All Grades ()
Fatigue 58
Diarrhea 58
Nausea 49
Altered taste 44
Mucositis/stomatitis 43
Anorexia 38
Hypertension 30
Bleeding 30
Vomiting 28
Dyspepsia 28
Rash 27
Abdominal pain 22
Hand-foot syndrome 21
Sutent (sunitinib) Full Prescribing Information.
Pfizer Inc. October 2007.
25
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. 200853917-930.
2. Wilhelm SM, et al. Cancer Res.
2004647099-7109. 3. Ratain MJ, et al. J Clin
Oncol. 2006242505-2512. 4. Escudier B et al. N
Engl J Med. 2007356125.
26
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.
2006425-32.
27
SorafenibMost Common Adverse Events (20)
Adverse Event All Grades ()
Diarrhea 55
Fatigue 46
Abdominal pain 31
Weight loss 30
Anorexia 29
Nausea 24
Hand-foot reaction 21
Nexavar (sorafenib) Full Prescribing
Information. Bayer HealthCare. 2008.
28
Sunitinib and Sorafenib Adverse EventsNursing
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. 2007319-20. 2.
Wood LS. Oncology Nurs News. 2007437-38.
29
Sunitinib and Sorafenib Adverse EventsNursing
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. 2007319-20. 2.
Wood LS. Oncology Nurs News. 2007437-38.
30
Sunitinib and Sorafenib Adverse EventsNursing
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 Crème
• Biafine Topical Emulsion

1. Wood LS. Oncology Nurs News. 2007319-20. 2.
Wood LS. Oncology Nurs News. 2007437-38.
31
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.
32
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.
2005237889-7996. 2. Bukowski RM, et al. J Clin
Oncol. 2007254536-4541.
33
Bevacizumab Serious Adverse Events (10)
Adverse Event Bevacizumab 10 mg/kg (N39) Bevacizumab 3 mg/kg (N37)
Epistaxis 21 14
Hypertension 36 (21)a 3
Fever without infection 10 3
Malaise 33 16
Hematuria 13 3
Hyponatremia 8 11
Proteinuriab 64 (8)a 41 (5)a
Elevated ALT 10 5
Chest pain 5 (5)a 0
aPercent of patients with grade 3 toxic
effects b1 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 gt3.5 g of protein per 24 hrs
Yang CH, et al. N Engl J Med. 2003349427-434.
34
Bevacizumab Adverse EventsNursing 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. 200461(Suppl
5)21-26.
35
Bevacizumab Adverse EventsNursing 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. 200461(Suppl
5)21-26.
36
Temsirolimus

• An inhibitor of mammalian target of rapamycin
  (mTOR) kinase, a component of intracellular
  signaling pathways1
• Binds to an abundant intracellular protein
  FKBP-12, 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. 2000103253-262.
• 2. Skotnicki JS, et al. Clin Cancer Res.
  20017(Suppl)3749-3750.
• 3. Harding MW. Clin Cancer Res. 200392882-2886.

37
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 25?50 mg IV prior to the start of
  each dose
• If patient develops a hypersensitivity reaction
  during infusion
• Stop infusion
• Observe patient at least 30?60 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.
38
TemsirolimusMost Common Adverse Events (30)
Adverse Event All Grades ()
Asthenia 51
Rash 47
Mucositis 41
Nausea 37
Edema 35
Anorexia 32
Torisel (temsirolimus) Full Prescribing
Information. Wyeth Pharmaceuticals. May 2007.
39
Temsirolimus Adverse EventsNursing 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

40
Temsirolimus Adverse EventsNursing 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

41
Temsirolimus Adverse EventsNursing 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.
42
Temsirolimus Adverse EventsNursing 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.
43
NCCN GuidelinesExplanation 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.
44
NCCN GuidelinesExplanation 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.
45
NCCN Practice Guidelines in Oncology Kidney
Cancer
FIRST-LINE THERAPY
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
Predominant clear cell histology
Relapse or Stage IV and medically or surgically
unresectable
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.
2007v. 1. 2008.
46
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.
2007v. 1. 2008.
47
NCCN Practice Guidelines in OncologyKidney
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
Progression
aBest supportive care can include palliative RT,
metastasectomy or biphosphonates for bony
metastasis
NCCN Clinical Practice Guidelines in Oncology.
2007v. 1. 2008.
48
Targeted TherapiesPatient 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.
49
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)

50
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?