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Nancy Moldawer, RN, MSN Clinical Research Operations Manager Division of Medical Oncology and Therapeutic Research City of Hope Duarte, California
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.
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
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
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
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
1015%
510%
1. Thoenes W et al. Path Res Pract. 1986;181:125. 2. Strkel S, van den Berg E. World J Urol. 1995;13:153.
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.
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
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.
Growth Factors
Vascular endothelial growth factor (VEGF) key growth factor involved in angiogenesis1,2
VEGF mRNA expression correlates with vascularization
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.
bevacizumab
sorafenib, sunitinib
VEGF
EGF
gefitinib, cetuximab, erlotinib, panitumumab
MEK
mTOR
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%
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
1. Abrams TJ, et al. Mol Cancer Ther. 2003;2:471-478. 2. Motzer RJ. JAMA. 2006;295:2516-2524.
May be taken with or without food Sunitinib and its active metabolite metabolized primarily by CYP3A4
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.
Sorafenib
An orally administered multikinase inhibitor
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.
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.
1. Hainsworth JD, et al. J Clin Oncol. 2005;23:7889-7996. 2. Bukowski RM, et al. J Clin Oncol. 2007;25:4536-4541.
%
Epistaxis 21
%
14
Hypertension
Fever without infection
36 (21)a
10
3
3
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.
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.
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
Anemia
Monitor hemoglobin and hematocrit regularly during therapy
Anorexia
Maximize caloric intake
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
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
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
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
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.
Progression
aBest
supportive care can include palliative RT, metastasectomy or biphosphonates for bony metastasis
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?