Radiation Safety Guidelines for Radioimmunotherapy with Yttrium 90 Ibritumomab Tiuxetan

FEATURE ARTICLE

This material is protected by U.S. copywright law. Unauthorized reproduction is prohibited. To purchase reprints or request permission to reproduce, e-mail [email protected]. Radiation Safety Guidelines for Radioimmunotherapy With Yttrium 90 Ibritumomab Tiuxetan

Carolyn Hendrix, RN, OCN®

n 2003, approximately ies for tumor cell surface anti- 53,400 people in the United Radioimmunotherapy is a new cancer therapy that com- gens (Potamianos, Varvarigou, I States were diagnosed bines the cytotoxicity of radiation with the tumor-specific & Archimandritis, 2000). Non- with non-Hodgkin’s lymphoma targeting of monoclonal antibodies. Yttrium 90 (Y-90) radiolabeled, or “cold,” mono- (NHL), making it the sixth most clonal antibody therapy for re- ™ common cancer in the United ibritumomab tiuxetan (Zevalin , IDEC Pharmaceuticals lapsed indolent NHL has been States (American Cancer Soci- Corporation, San Diego, CA) is indicated for the treatment shown to produce a 48% overall ety, 2003). Unlike most other of patients with relapsed or refractory low-grade, follicular, response rate in NHL that has re- malignancies, the incidence and lapsed after treatment with che- mortality of NHL are increasing or transformed B-cell non-Hodgkin’s lymphoma (NHL), motherapy, with the median du- (McKean-Cowdin, Feigelson, including patients with rituximab-refractory follicular ration of response of 11.8 Ross, Pike, & Henderson, 2000). NHL. Y-90 ibritumomab tiuxetan requires only universal months (McLaughlin et al., Conventional cancer therapies safety precautions and does not impose undue risks or ra- 1998). Still, the median survival such as chemotherapy and ex- after a diagnosis of follicular ternal beam radiation have not diation safety restrictions on patients or healthcare work- NHL remains approximately 8– proved successful in curing ers. The ibritumomab tiuxetan regimen can be adminis- 12 years (Reiser & Diehl, 2002). most forms of indolent, low- tered safely in an outpatient setting. Nurses should become However, RIT can deliver grade, or follicular forms of familiar with the necessary precautions in caring for pa- higher doses of radiation to tar- NHL. Furthermore, these con- geted tumors than to nearby ventional therapies often are as- tients treated with Y-90 ibritumomab tiuxetan, both to edu- healthy organs (Press et al., sociated with significant toxic cate patients about safety issues and to minimize the risk 1993; Wiseman et al., 2001). effects in patients. of radiation exposure to staff and others. After the delivery of the radio- Disseminated disease typi- nuclide to malignant tissue by cally has been treated with che- Key Words: radioimmunotherapy, safety the antibody’s targeting of the motherapy, external beam radio- antigen, cancer cells are killed therapy, immunotherapy, or a combination of nuclear medicine facilities will need to un- by a combination of the targeted radiation, these three modalities. Chemotherapy has derstand radiation safety issues and prac- the biologic effect of the monoclonal anti- limited efficacy and, often, burdensome tox- tices. Additionally, nursing staff already fa- body, and the crossfire effect of the radia- icity. External beam radiation is not tumor miliar with conventional radiotherapy tion on nearby tumor cells to which the anti- specific, and it delivers the same amount of treatment modalities will need to become fa- body did not bind (e.g., because of physical radiation to healthy organs as it does to tu- miliar with the new, often less demanding, inaccessibility, because the tumor cell did mor sites, thereby limiting the dose of radia- safety requirements of RIT. This article re- tion that can be given. Recent advances in ra- views the basics of radiation safety and dis- Submitted June 2003. Accepted for publica- diation therapy, such as those used with cusses the necessary precautions in caring tion August 29, 2003. (Mention of specific conformal radiation and intensity-modulated for patients treated with the yttrium 90 (Y- products and opinions related to those prod- radiation therapy technology, target tumors 90) ibritumomab tiuxetan RIT regimen ucts do not indicate or imply endorsement by with a higher dose of radiation while deliver- (Zevalin™, IDEC Pharmaceuticals Corpo- the Clinical Journal of Oncology Nursing or ing less radiation exposure to adjacent tissue. ration, San Diego, CA). the Oncology Nursing Society.) Carolyn Hen- However, this technology is not yet widely drix, RN, OCN ®, is a member of the IDEC available or necessarily appropriate for treat- Radioimmunotherapy Speakers’ Bureau. IDEC Pharmaceuticals ing disorders such as lymphoma. Corporation is the manufacturer of Zevalin™ As the use of radioimmunotherapy (RIT) RIT is an approved treatment modality (yttrium 90 ibritumomab tiuxetan). becomes more widespread, nursing staff that combines the cytotoxicity of radiation outside traditional radiation oncology or with the specificity of monoclonal antibod- Digital Object Identifier: 10.1188/04.CJON.31-34

CLINICAL JOURNAL OF ONCOLOGY NURSING • VOLUME 8, NUMBER 1 • RADIATION SAFETY GUIDELINES FOR RADIOIMMUNOTHERAPY 31 not express the antigen being targeted) zig, Flinn, et al., 2002; (Illidge & Johnson, 2000). Witzig, Gordon, et al., 2002). Safety Guidelines for Radioimmunotherapy Ibritumomab Tiuxetan Radiation safety focuses on three key ar- eas: using appropriate shielding during ad- Regimen ministration, minimizing exposure time, and maximizing distance from the radiation The ibritumomab tiuxe- source. Determining the appropriate mate- tan regimen is a single- treatment course that is rial and thickness for shielding depends largely on the type of radiation emitted by given on two days approxi- the radionuclide. Most oncology nurses are mately one week apart (IDEC Pharmaceuticals 111 familiar with the radionuclide iodine 131, In—indium 111; Y-90—yttrium 90 which typically has been used to treat thy- Corporation, 2002) (see roid disease. Iodine 131 emits gamma ra- Figure 2). On the first day FIGURE 2. IBRITUMOMAB TIUXETAN THERAPEUTIC REGIMEN of the ibritumomab tiuxe- diation, and in most instances, its use re- Note. Reprinted with permission from IDEC Pharmaceuticals, Inc., quires patient isolation, lead shielding tan regimen, the patient is San Diego, CA. during administration, and strict safety pre- given an infusion of rituximab 250 mg/m2, fol- cautions after patient discharge. The ibritumomab tiuxetan regimen, however, uses lowed within four hours by a tracer dose of staff will be involved in counseling patients, the radionuclide Y-90, which is a pure beta indium 111 ibritumomab tiuxetan 5 mCi (1.6 obtaining insurance authorization, and edu- mg) injected slowly over 10 minutes. Whole cating patients and their families and emitter. Therefore, fewer precautions are necessary when using this agent. body planar anterior and posterior view caregivers about radiation safety and fol- gamma images are obtained at 2–24 hours low-up care. Coding and reimbursement in- and 48–72 hours after this imaging dose of formation, which was revised in 2003, is Yttrium 90 indium 111 ibritumomab tiuxetan to assess available online at www.zevalin.com/pdfs/ Ibritumomab Tiuxetan the biodistribution of the tracer dose; an op- Billing_Guide.pdf. In addition, IDEC Phar- tional third image can be obtained at 90–120 maceuticals Corporation offers a reim- Y-90 ibritumomab tiuxetan consists of hours to resolve any ambiguities. If the bursement assistance program, RESULTS™ ibritumomab, a murine monoclonal anti- biodistribution is as expected, on regimen for Zevalin, which provides assistance with body to the CD20 antigen stably bound to days 7, 8, or 9, the therapeutic dose of Y-90 reimbursement and coding issues as well as tiuxetan, which chelates the radionuclide Y- ibritumomab tiuxetan (0.4 mCi/kg if the programs for the uninsured (800-386-9997, 90 (see Figure 1). Ibritumomab is the par- patient’s platelet count is > 150,000/mm3 or phone; 800-513-8055, fax; www.zevalin ent of the chimeric monoclonal antibody 0.3 mCi/kg if the patient’s platelet count is .com/html/HealthcareProfessionals/Reim rituximab. In clinical trials, Y-90 ibritumo- 100,000–149,000/mm3) is injected slowly bursement/results.html, Web site). mab tiuxetan has produced overall response over 10 minutes and again within four hours rates of 73%–83% in indolent, low-grade, after the administration of rituximab 250 or follicular NHL (Wiseman et al., 2002; mg/m2. The maximum dose of Y-90 ibritu- Safety of Yttrium 90 Witzig, Emmanouilides, et al., 2003; Wit- momab tiuxetan is 32 mCi (IDEC Pharma- Ibritumomab Tiuxetan ceuticals Corporation). Nurses play a key role in co- Y-90 emits only beta radiation, which has ordinating rituximab infusions a mean effective path length of approxi- Monoclonal antibody given before the imaging and mately 5 mm in soft tissue (i.e., 90% of the therapeutic doses of radioim- energy is absorbed within a sphere with a

munoconjugate. These rituxi- radius of 5 mm), and because of this, it does ▲ mab infusions are given to im- not penetrate outside the patient’s body. This prove the biodistribution of the form of radiation is absorbed by approxi- Y-90 ibritumomab tiuxetan to mately 1 cm of acrylic; therefore, fewer the tumor sites. The predose of safety precautions are required in using Y- ▲ rituximab binds to readily acces- 90 ibritumomab tiuxetan than in using ra- ▲ ▲ sible CD20 sites on cells in the dionuclides such as iodine 131 that emit peripheral blood and prevents in- gamma rays (Wagner et al., 2002). Beta ▲ discriminate uptake of the radio- emissions pose minimal radiation hazards to labeled antibody in the reticu- healthcare workers or patients’ contacts; as Beta loendothelial system (Wagner et a result, the ibritumomab tiuxetan regimen radiation Chelator Y-90 radionuclide al., 2002). can be administered on an outpatient basis Y-90—yttrium 90 Nurses also are integral in using only universal precautions for radia- providing patient care through- tion safety. Acrylic shielding is required FIGURE 1. YTTRIUM 90 IBRITUMOMAB TIUXETAN out the regimen of ibritumomab (acrylic vial and syringe shields are avail- Note. Reprinted with permission from IDEC Pharmaceuticals, tiuxetan administration. Before able [see Figure 3]), and patient isolation is Inc., San Diego, CA. treatment is initiated, nursing unnecessary (see Figure 4). Lead shielding

32 FEBRUARY 2004 • VOLUME 8, NUMBER 1 • CLINICAL JOURNAL OF ONCOLOGY NURSING TABLE 1. RADIATION EXPOSURE

LEVEL OF EXPOSURE AMOUNT OF EXPOSURE

Chest x-ray ~ 20 mrem Average person in the United States 360 mrem/year Average hospital radiation worker in the United States + 150 mrem/year (510 mrem/year total) Radiation sickness from single dose > 100 rem Immune system, vascular damage > 300 rem

Note. Based on information from Cohen & Lee, 1979; Gotchy, 1978; Kelsey, 1978.

• Syringe shield conveniently holds a 12 cc syringe for infusion of yttrium 90 Zevalin™ anticipate and address any side effects that Because many patients with NHL who are • Vial shield opens on one end to allow insertion occur. treated with RIT already have been treated of 10 cc reaction vial; other end opens to allow In Y-90 ibritumomab tiuxetan, the chela- with several other therapies, nurses must edu- for drawing out of the vial tor stably binds the radionuclide to the anti- cate patients about the differences between body. Urinary excretion, the primary route of RIT and traditional cancer therapies. FIGURE 3. ACRYLIC SYRINGE AND VIAL SHIELDS elimination, accounts for the elimination of Most patients who are treated with Y-90 Note. Reprinted with permission from IDEC Phar- only 7.3% ± 3.2% of the administered dose ibritumomab tiuxetan are outpatients. maceuticals, Inc., San Diego, CA. over seven days (Wagner et al., 2002). Therefore, the nursing staff at outpatient fa- For the first three days after treatment, cilities must be trained in radiation safety. should not be used in the ibritumomab patients should be instructed to clean any Many nuclear medicine or radiation therapy tiuxetan regimen because of the risk of exac- spilled urine, properly dispose of any mate- departments are licensed to administer RIT. erbating the radiation through the brems- rials contaminated with body fluids, and Most nursing staff members will not be in- strahlung effect (i.e., radiation produced by wash their hands thoroughly after using a volved directly in administering the radiola- an electronic particle when it is subjected to a toilet. In addition, they should be advised to beled components of the ibritumomab tiuxe- sudden stop). use condoms for sexual relations for the first tan regimen, but they should be familiar with Therapy with Y-90 ibritumomab tiuxetan week after treatment, to avoid pregnancy for safety guidelines. Nurses typically are re- is generally well tolerated. Most of the non- one year, and, if breastfeeding, to discon- sponsible for administering infusions of hematologic side effects that do occur can tinue and replace with formula (IDEC Phar- rituximab, and they also may assist with pa- be attributed to the infusions of rituximab maceuticals Corporation, 2002; Wagner et tient care activities such as implanted port given before radiolabeled ibritumomab al., 2002). A study in which patients ob- access or management of the side effects of tiuxetan; hematologic side effects such as served these precautions showed that the monoclonal antibodies. neutropenia and thrombocytopenia most of- family member who had closest contact with Nurses continually find themselves on the ten are predictable, transient, and manage- the patient had minimal radiation exposure cutting edge of clinical practice. As modali- able (Witzig, White, et al., 2003). Oncol- of 3.5 mrem over seven days, which is in ties move from research to clinical practice, ogy nurses should be familiar with the side the range of everyday background radiation nurses must be familiar with new patient effects of rituximab and should be prepared (Wiseman, Leigh, Witzig, Gansen, & White, care requirements. to counsel patients about potential side ef- 2000) (see Table 1). fects; in addition, nurses should be able to Implications for Practice Conclusion As RIT use increases and other tumors are The ibritumomab tiuxetan regimen pre- targeted for treatment, nurses in all treat- For three days after treatment sents oncology nurses with new opportuni- ment settings must have a working knowl- • Clean spilled urine and dispose of material con- ties for collaboration and education. Because taminated with body fluid (i.e., flush down a toi- edge of RIT. Because oncology nurses edu- of regulatory, safety, and administrative re- let or place in a plastic bag in household trash) cate patients and caregivers about treatments quirements, RIT necessitates a multidisci- so that others will not inadvertently handle it. and their safety, patients will look to them plinary approach among oncology nurses, • Wash hands thoroughly after using a toilet. for reassurance that Y-90 ibritumomab oncology physicians, nuclear medicine and tiuxetan therapy requires few and relatively For one week after treatment radiation therapy personnel, radiopharma- • Use condoms for sexual relations. minor safety precautions. cists, and radiation safety officers. In this For one year after treatment team approach, oncology nurses play a key • Avoid pregnancy. role in ensuring continuity throughout the Author Contact: Carolyn Hendrix, RN, ® If breastfeeding, discontinue and replace with treatment and, because they are the members OCN , can be reached at chendrix@hoag formula. (Duration has yet to be determined; the of the team with the most direct and ongoing hospital.org. potential for Zevalin exposure in infants is un- contact with patients, they are in a unique known.) position to counsel patients, families, and caregivers, as well as educate them about the References FIGURE 4. YTTRIUM 90 IBRITUMOMAB various aspects of cancer care (Volker, 1992), American Cancer Society. (2003). Cancer facts TIUXETAN PATIENT RELEASE INSTRUCTIONS including the precautions necessary to pre- and figures, 2003. Atlanta, GA: Author. Note. Based on information from IDEC Pharma- vent radiation exposure to others during and Cohen, B.L., & Lee, I.S. (1979). A catalog of ceutical Corporation, 2002; Wagner et al., 2002. after Y-90 ibritumomab tiuxetan treatment. risks. Health Physics, 36, 707–722.

CLINICAL JOURNAL OF ONCOLOGY NURSING • VOLUME 8, NUMBER 1 • RADIATION SAFETY GUIDELINES FOR RADIOIMMUNOTHERAPY 33 Gotchy, R.L. (1978). Estimation of life shortening Nabi, H.A., Nagle, C.E., Fink-Bennett, D.M., rituximab-refractory follicular non-Hodgkin’s resulting from radiogenic cancer per rem of et al. (2002). Administration guidelines for lymphoma. Journal of Clinical Oncology, 20, absorbed dose. Health Physics, 35, 563–565. radioimmunotherapy of non-Hodgkin’s lym- 3262–3269. IDEC Pharmaceuticals Corporation. (2002). phoma with 90Y-labeled anti-CD20 monoclonal Witzig, T.E., Gordon, L.I., Cabanillas, F., Zevalin™ (ibritumomab tiuxetan) [Prescribing antibody. Journal of Nuclear Medicine, 43, Czuczman, M.S., Emmanouilides, C., Joyce, information]. San Diego, CA: Author. 267–272. R., et al. (2002). Randomized controlled trial of Illidge, T.M., & Johnson, P.W. (2000). The Wiseman, G., Leigh, B., Witzig, T., Gansen, D., yttrium-90–labeled ibritumomab tiuxetan ra- emerging role of radioimmunotherapy in & White, C. (2000). Radiation exposure is very dioimmunotherapy versus rituximab immuno- haematological malignancies. British Journal low to the family members of patients treated therapy for patients with relapsed or refractory of Haematology, 108, 679–688. with yttrium-90 Zevalin™ anti-CD20 mono- low-grade, follicular, or transformed B-cell Kelsey, C.A. (1978). Comparison of relative risk clonal antibody therapy for lymphoma [Ab- non-Hodgkin’s lymphoma. Journal of Clinical from radiation exposure and other common stract]. European Journal of Nuclear Medicine, Oncology, 20, 2453–2463. hazards. Health Physics, 35, 428–430. 28, 1198. Witzig, T.E., White, C.A., Gordon, L.I., Wise- McKean-Cowdin, R., Feigelson, H.S., Ross, R.K., Wiseman, G.A., Gordon, L.I., Multani, P.S., Wit- man, G.A., Emmanouilides, C., Murray, J.L., et Pike, M.C., & Henderson, B.E. (2000). Declin- zig, T.E., Spies, S., Bartlett, N.L., et al. (2002). al. (2003). Safety of yttrium-90 ibritumomab ing cancer rates in the 1990s. Journal of Clini- Ibritumomab tiuxetan radioimmunotherapy for tiuxetan radioimmunotherapy for relapsed low- cal Oncology, 18, 2258–2268. patients with relapsed or refractory non- grade, follicular, or transformed non-Hodg- McLaughlin, P., Grillo-Lopez, A.J., Link, B.K., Hodgkin’s lymphoma and mild thrombo- kin’s lymphoma. Journal of Clinical Oncology, Levy, R., Czuczman, M.S., Williams, M.E., et cytopenia: A phase II multicenter trial. Blood, 21, 1263–1270. al. (1998). Indolent lymphoma: Half of patients 99, 4336–4342. respond to a four-dose treatment program. Wiseman, G.A., White, C.A., Sparks, R.B., Er- Journal of Clinical Oncology, 16, 2825–2833. win, W.D., Podoloff, D.A., Lamonica, D., et Continuing education credit for this and Potamianos, S., Varvarigou, A.D., & Archiman- al. (2001). Biodistribution and dosimetry re- other CJON articles is available in the dritis, S.C. (2000). Radioimmunoscintigraphy sults from a phase III prospectively random- Publications area of www.ons.org. and radioimmunotherapy in cancer: Principles ized controlled trial of Zevalin radioimmu- and application. Anticancer Research, 20, 925– notherapy for low-grade, follicular, or trans- 948. formed B-cell non-Hodgkin’s lymphoma. Press, O.W., Eary, J.F., Appelbaum, F.R., Martin, Critical Reviews in Oncology and Hematol- P.J., Badger, C.C., Nelp, W.B., et al. (1993). ogy, 39, 181–194. For more information on this topic, Radiolabeled-antibody therapy of B-cell lym- Witzig, T.E., Emmanouilides, C., Molina, A., visit the following Web sites. phoma with autologous bone marrow support. Gordon, L.I., Gaston, I., Flinn, I.W., et al. New England Journal of Medicine, 329, 1219– (2003). Yttrium-90 ibritumomab tiuxetan American Cancer Society: Yttrium 90 1224. radioimmunotherapy (RIT) induces durable Ibritumomab Therapy Reiser, M., & Diehl, V. (2002). Current treatment complete responses (CR/CRu) in patients with www.cancer.org/docroot/CDG/content/ of follicular non-Hodgkin’s lymphoma. Euro- relapsed or refractory B-cell non-Hodgkin’s CDG_90_yttrium_(90Y)_ibritumomab pean Journal of Cancer, 38, 1167–1172. lymphoma (NHL) [Abstract]. Procedures of _tiuxetan.html Volker, D. (1992). Standards of oncology educa- the American Society of Clinical Oncology, 22, tion: Patient, family, and public. In J.C. Clark 597. Radiation Safety Academy & R.F. McGee (Eds.), Core curriculum for Witzig, T.E., Flinn, I.W., Gordon, L.I., Em- www.radtrain.com oncology nursing (2nd ed., pp. 18–24). Phila- manouilides, C., Czuczman, M.S., Saleh, M.N., delphia: Saunders. et al. (2002). Treatment with ibritumomab Links can be found at www.ons.org. Wagner, H.N., Jr., Wiseman, G.A., Marcus, C.S., tiuxetan radioimmunotherapy in patients with

Rapid Recap Radiation Safety Guidelines for Radioimmunotherapy With Yttrium 90 Ibritumomab Tiuxetan • Radioimmunotherapy, an approved treatment option for certain types of non-Hodgkin’s lymphoma, combines the cyto- toxic effects of radiation with the tumor-specific targeting of monoclonal antibodies. • Yttrium 90 (Y-90), the therapeutic radionuclide used with ibritumomab tiuxetan, is a pure beta emitter that poses fewer risks to patients, caregivers, and healthcare staff than conventional radionuclides (e.g., iodine 131), which emit both beta and gamma radiation. • The ibritumomab tiuxetan regimen is a single-treatment course that is given on two days approximately one week apart. • Universal safety precautions apply with Y-90 ibritumomab tiuxetan therapy. • For the first three days after treatment, patients should be instructed to clean any spilled urine, properly dispose of any materials contaminated with body fluids, and wash their hands thoroughly after using a toilet. • Family members and friends need to be reassured that close contact with the patient is not harmful. Minimal radiation exposure, which is in the range of everyday background radiation, is associated with this treatment.

34 FEBRUARY 2004 • VOLUME 8, NUMBER 1 • CLINICAL JOURNAL OF ONCOLOGY NURSING