Article

Ipilimumab for Advanced Melanoma: A Nursing Perspective

Blanca Ledezma

melanoma
ONF 2009, 36(1), 97-104. DOI: 10.1188/09.ONF.97-104

Purpose/Objectives: To discuss the response patterns and side effects related to ipilimumab, a new immunotherapeutic agent under investigation in the treatment of advanced melanoma and other malignancies.

Data Sources: Published articles, abstracts, research data, and clinical experience.

Data Synthesis: Ipilimumab is a fully human monoclonal antibody that inhibits the activity of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a naturally immunosuppressive molecule. The most common side effects are immune mediated (e.g., inflammatory diarrhea, pruritis) and appear to occur as a direct result of CTLA-4 inhibition and enhanced immune system activation. Side effects generally are grade I or II and resolve with standard treatments. Most grade III or IV events are managed successfully after swift diagnosis and treatment with corticosteroids; steroid-refractory events resolve after treatment with infliximab or mycophenolate.

Conclusions: The response patterns and side effects associated with ipilimumab therapy greatly differ from those common to other advanced melanoma therapies (e.g., chemotherapy, cytokines, vaccines).

Implications for Nursing: Nurses have an important role in educating patients about the differences between anti-CTLA-4 therapy and chemotherapy. In addition, teaching patients to recognize ipilimumab's side effects and report them early can result in fast treatment to prevent symptom progression from grade I or II to III or IV. Communication between nurses and patients throughout the treatment process will help patients benefit maximally from the new therapeutic strategy.

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    References

    American Cancer Society. (2008). Cancer facts and figures, 2008. Atlanta, GA: Author.
    Antonia, S., Sosman, J., Kirkwood, J. M., Redman, B., Gajewski, T. F., Pavlov, D., et al. (2007). Natural history of diarrhea associated with the anti-CTLA-4 monoclonal antibody CP-675,206 [Abstract 3038]. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings, 25 (18, Suppl.), 127S.
    Atkins, M. B., Lotze, M. T., Dutcher, J. P., Fisher, R. I., Weiss, G., Margolin, K., et al. (1999). High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: Analysis of 270 patients treated between 1985 and 1993. Journal of Clinical Oncology, 17(7), 2105-2116.
    Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., et al. (2005). Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. Journal of Clinical Oncology, 23(25), 6043-6053.
    Balch, C. M., Buzaid, A. C., Soong, S. J., Atkins, M. B., Cascineffi, N., Coit, D. G., et al. (2001). Final version of the American Joint Committee on cancer staging system for cutaneous melanoma. Journal of Clinical Oncology, 19(16), 3635-3648.
    Beck, K. E., Blansfield, J. A., Tran, K. Q., Feldman, A. L., Hughes, M. S., Royal, R. E., et al. (2006). Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. Journal of Clinical Oncology, 24(15), 2283-2289.
    Bedikian, A. Y., Millward, M., Pehamberger, H., Conry, R., Gore, M., Trefzer, U., et al. (2006). Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma. Journal of Clinical Oncology, 24(29), 4738-4745.
    Blansfield, J. A., Beck, K. E., Tran, K., Yang, J. C., Hughes, M. S., Kammula, U. S., et al. (2005). Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. Journal of Immunotherapy, 28(6), 593-598.
    Chin, K., Ibrahim, R., Berman, D., Yellin, M., Lowy I., Lin, R., et al. (2008). Treatment guidelines for the management of immune-related adverse events in patients treated with ipilimumab, an anti-CTLA4 therapy [Abstract 787]. Annals of Oncology, 19(Suppl. 8), vii244-vii245.
    Fischkoff, S. A., Hersh, E., Weber, J., Powderly, J., Khan, K., Pavlick, A., et al. (2005). Durable responses and long-term progression-free survival observed in a phase II study of MDX-010 alone or in combination with dacarbazine (DTIC) in metastatic melanoma [Abstract 7525]. Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings, 23(16, Suppl.), 716S.
    Hamid, O., Chin, K., Li, J., Neyns, G., Linette, S., Negrier, J., et al. (2008). Dose effect of ipilimumab in patients with advanced melanoma: Results from a phase II, randomized, dose-ranging study [Abstract 9025]. Retrieved December 16, 2008, from http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=35387
    Hamid, O., Urba, W. J., Yellin, M., Nichol, G. M., Weber, J., Hersh, E. M., et al. (2007). Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma [Abstract 8525]. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings, 25(18, Suppl.), 478S.
    Levy, C. (2007). Early detection and management of adverse events associated with ipilimumab: How the research nurse plays a vital role [Abstract 2375]. Oncology Nursing Forum, 34(2), 563-564.
    Maker, A. V., Phan, G. Q., Attia, P., Yang, J. C., Sherry, R. M., Topalian, S. L., et al. (2005). Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: A phase I/II study. Annals of Surgical Oncology, 12(12), 1005-1016.
    Maker, A. V., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., et al. (2006). Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma. Journal of Immunotherapy, 29(4), 455-463.
    O'Day, S., & Boasberg, P. (2006). Management of metastatic melanoma, 2005. Surgical Oncology Clinics of North America, 15(2), 419-437.
    O'Day, S., Ibrahim, V., DePril, M., Maio, V., Chiaron-Sileni, T., Gajewski, H., et al. (2008). Efficacy and safety of ipilimumab induction and maintenance dosing in patients with advanced melanoma who progressed on one or more prior therapies [Abstract 9021]. Retrieved December 16, 2008, from http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=35146
    Peggs, K. S., Quezada, S. A., Korman, A. J., & Allison, J. P. (2006). Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Current Opinion in Immunology, 18(2), 206-213.
    Quirt, I., Verma, S., Petrella, T., Bak, K., & Charette, M. (2007). Temozolomide for the treatment of metastatic melanoma: A systematic review. Oncologist, 12(9), 1114-1123.
    Reuben, J. M., Lee, B. N., Li, C., Gomez-Navarro, J., Bozon, V. A., Parker, C. A., et al. (2006). Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in patients with advanced malignant melanoma. Cancer, 106(11), 2437-2444.
    Ribas, A., Camacho, L. H., Lopez-Berestein, G., Pavlov, D., Bulanhagui, C. A., Millham, R., et al. (2005). Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. Journal of Clinical Oncology, 23(35), 8968-8977.
    Ries, L. A. G., Melbert, D., Krapcho, M., Mariotto, A., Miller, B. A., Feuer, E. J., et al. (2007). SEER cancer statistics review, 1975-2004. Bethesda, MD: National Cancer Institute. Retrieved November 19, 2008, from http://seer.cancer.gov/csr/1975_2004/ http://seer.cancer.gov/csr/1975_2004/
    Rosenberg, S. A., Yang, J. C., & Restifo, N. P. (2004). Cancer immuno-therapy: Moving beyond current vaccines. Nature Medicine, 10(9), 909-915.
    Schering Corporation. (2008). INTRON® A (interferon alfa-2b) [Prescribing information]. Kenilworth, NJ: Author.
    Tarhini, A. A., Kirkwood, J. M., Gooding, W. E., Cai, C., & Agarwala, S. S. (2007). Durable complete responses with high-dose bolus interleukin-2 in patients with metastatic melanoma who have experienced progression after biochemotherapy. Journal of Clinical Oncology, 25(25), 3802-3807.
    Weber, J. S. (2007). Anti-CTLA-4 antibody ipilimumab: Case studies of clinical response and immune-related adverse events. Oncologist, 12(7), 864-872.
    Weber, J. S., Berman, D., Siegel, J., Minor, D., Amin, A., Thompson, J., et al. (2008). Safety and efficacy of ipilimumab with or without prophylactic budesonide in treatment-naive and previously treated patients with advanced melanoma [Abstract 9010]. Retrieved December 16, 2008, from http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=34769
    Weber, J. S., Hersh, E. M., Yellin, M. J., Nichol, G. M., Urba, W., Powderly, J. D., et al. (2007). The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma [Abstract 8523]. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings, 25 (18, Suppl.), 477S.