Administration-approved indications and routes of administration for the following targeted agents: sunitinib, sorafenib, bevacizumab, temsirolimus, everolimus ...
SITE-SPECIFIC CANCERS
Nursing Management of Renal Cell Carcinoma in the New Era of Targeted Therapy At a Glance Clinical trials have shown that targeted agents can prolong survival for patients with metastatic renal cell carcinoma by inhibiting key pathways involved in angiogenesis and tumor growth. Nurses need to identify common adverse effects associated with these agents, help patients manage the effects so that treatment can be continued, and provide support and guidance for patients receiving oral targeted therapies.
S
peaker Robert A. Figlin, MD, began by showing clear cell carcinoma as the most common (75% frequency) of the renal cell carcinoma (RCC) histologic subtypes. He recapped the history of RCC treatment, beginning with the cytokines interleukin-2 and interferon alfa in 1982 up through the targeted therapies used for the past 10 years (see Figure 1). He reviewed the U.S. Food and Drug Administration-approved indications and routes of administration for the following targeted agents: sunitinib, sorafenib, bevacizumab, temsirolimus, everolimus, and pazopanib. Phase III trials have demonstrated significant activity for sunitinib (Figlin et al., 2008), sorafenib (Escudier, Eisen, et al., 2007), bevacizumab (Escudier, Pluzanska, et al., 2007; Rini et al., 2008), temsirolimus (Hudes et al., 2007), everolimus (Kay et al., 2009) and pazopanib (Sternberg et al., 2009). Ongoing studies are assessing targeted agent combinations and compara-
tive effectiveness, such as the BeST trial studying different combinations of bevacizumab, temsirolimus, and sorafenib versus bevacizumab alone in treating patients with metastatic kidney cancer (http://clinicaltrials.gov/ ct2/show/NCT00378703) and the INTORACT trial comparing bevacizumab plus temsirolimus versus bevacizumab plus interferon alfa in advanced RCC (http://clinicaltrials.gov/ct2/show/ NCT00631371). Questions remain regarding the optimal dosing, sequencing, and combinations of targeted agents, as well as their toxicity, and further evaluation of tumor resistance to select targeted therapies and treatment options for non-clear-cell RCC is needed. Laura S. Wood, RN, MSN, OCN ®, reviewed the nurse’s role in managing the adverse effects of angiogenesis inhibitors. She began with the toxicity profile and laboratory abnormalities of sorafenib and sunitinib. Hypothyroidism is a side effect of sunitinib and is managed with levothyroxine. Dermatologic toxicities include dry skin, rash, hand-foot skin reaction (HFSR), desquamation, and skin discoloration. For managing HFSR, an interdisciplinary panel of experts developed an algorithm to guide practitioners (Lacouture et al., 2008). A variety of moisturizers, anti-itch and exfoliating agents, topical analgesics, and other skin care products are available to help manage dermatologic toxicities. Patients may experience hemorrhagic side effects such as epistaxis, which are managed
From ONS 35th Annual Congress in San Diego, CA, 2010
CBCE gratefully acknowledges the educational grant provided by Novartis Pharmaceuticals Corporation. Nursing Management of Renal Cell Carcinoma in the New Era of Targeted Therapy was held Thursday, May 13, 2010, at the San Diego Marriott Hotel and Marina in California. Presenters: Laura S. Wood, RN, MSN, OCN®, renal cancer research coordinator, Cleveland Clinic Taussig Cancer Center, Cleveland, OH (chairperson); Robert A. Figlin, MD, Arthur and Rosalie Kaplan Professor of Medical Oncology, Chair, Department of Medical Oncology, Beckman Research Institute, City of Hope National Medical Center, City of Hope Comprehensive Cancer Center, Duarte, CA; Nancy Moldawer, RN, MSN, clinical research operations manager, Department of Medical Oncology and Therapeutic Research, Nursing Coordinator- Kidney Cancer Program, City of Hope Medical Center. with a bedside humidifier or saline nasal spray, and rectal hemorrhoids, which is treated with over-the-counter antihemorrhoidal ointments. Wood presented a case study of a 60-year-old man who underwent a right nephrectomy for clear cell RCC and front-line therapy with sunitinib. During the second week of treatment, he experienced mild erythema and tenderness in the soles bilaterally, as well as mild mucositis and intermittent mild
35
SITE-SPECIFIC CANCERS Figure 1. Rapid Developments in Past 10 Years in Treatment of Renal Cell Carcinoma Cytokines: Immunotherapy: IL-2 Prognostic factors Bevacizumab + IFN-a: Euand IFN-afirst to report activity described ropean Medicines Agency approval in RCC VHL tumor suppressor gene Temsirolimus FDA isolated: First gene identified to approval: Based on cause a proportionof hereditary phase III data RCC and other tumors
1980s 80 81 82 83 84 85 86 87 88
1990s 89
90 91 92 93 94 95 96 97 98
High-dose IL-2 U.S. Food and Drug Administration (FDA) approval: Phase II data
diarrhea. By the third week, he had difficulty walking and found handling objects painful. Nursing management includes assessing (and modifying, as needed) the current skin care regimen; determining if the HFSR is grade 2 or 3 and if it is interfering with activities of daily living; and adhering to the “3 C” approach: control calluses, comfort with cushions, and cover with creams. Nursing Considerations Nancy Moldawer, RN, MSN, reviewed management strategies of mTOR inhibitors. Toxicities are highly variable, with most being grade 1–2 and 10%–20% developing into grade 3–4. Common adverse reactions to both temsirolimus and everolimus include asthenia, mucositis/stomatitis, rash, and nausea. Early recognition and aggressive management are key. Although no proven preventative treatment for mucositis exists, Moldawer said that its duration and severity may be reduced by an oral care regimen that includes rinsing four times per day with a bland rinse or baking soda mouthwash; using a 36
Bevacizumab: Data established activity of antiangiogenic agents in RCC
2000s 99
00 01 02 03 04 05 06 07 08
VEGFr TKI FDA approval: Sorafenib based on phase III and sunitinib based on phase II data
soft-bristled toothbrush; and avoiding chlorhexidine (alcohol-based) mouthwashes. Because mTOR inhibitors have immunosuppressive properties, patients may be predisposed to opportunistic pathogens. Nurses should monitor for and educate patients about signs and symptoms of infection. Noninfectious pneumonitis, an inflammation of the lungs not caused by infection, has been reported in some patients treated with everolimus. Symptoms may include cough, dyspnea, malaise, fever, hypoxia, or pleural effusion. Depending on severity, consultation with a pulmonologist or corticosteroids may be required. —Reporting by Mark Vrabel, MLS, AHIP, ELS References Escudier, B., Eisen, T., Stadler, W.M., Szczylik, C., Oudard, S., Siebels, M., . . . TARGET Study Group. (2007). Sorafenib in advanced clear-cell renal-cell carcinoma. New England Journal of Medicine, 356, 125–134. Escudier, B., Pluzanska, A., Koralewski, P., Ravaud, A., Bracarda, S., Szczylik, C., . . . AVOREN Trial investigators. (2007). Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet, 370, 2103–2111.
09
Everolimus, pazopanib FDA approval: Based on phase III data
Figlin, R.A., Hutson, T.E., Tomczak, P., Michaelson, M.D., Bukowski, R.M., Négrie, S., . . . Motzer, R.J. (2008). Overall survival with sunitinib vesus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC) [Abstract 5024]. Journal of Clinical Oncology, 26, 256s. Hudes, G., Carducci, M., Tomczak, P., Dutcher, J., Figlin, R., Kapoor, A., . . . Global ARCC Trial. (2007). Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. New England Journal of Medicine, 356, 2271–2281. Kay, A., Motzer, R, Figlin, R., Escudier, B., Oudard, S., Porta, C., . . . Ravaud, A. (2009). Updated data from a phase III randomized trial of everolimus (RAD001) versus PBO in metastatic renal cell carcinoma (mRCC). [Abstract 278]. American Society of Clinical Oncology Genitourinary Cancers Symposium. Retrieved from http://www.asco.org/ ASCOv2/Meetings/Abstracts?&vmview=abst_ detail_view&confID=64&abstractID=20488 Lacouture, M. E., Wu, S., Robert, C., Atkins, M. B., Kong, H. H., Guitart, J., . . . Dutcher, J. P. (2008). Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist, 13, 1001–1011. Rini, B.I., Halabi, S., Rosenberg, J.E., Stadler, W.M., Vaena, D.A., Ou, S.S., . . . Small, E. J. (2008). Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. Journal of Clinical Oncology, 26, 5422–5428. Sternberg, C.N., Szczylik, C., Lee, E., Salman, P.V., Mardiak, J., Davis, I.D., . . . Hawkins, R. (2009). A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokinepretreated patients with advanced renal cell carcinoma (RCC) [Abstract 5021]. Journal of Clinical Oncology, 27, 240s.
Spotlight on Symposia
