CONCLUSIONS
Continue Reading
The standard of care for patients with locoregional advanced or metastasized melanoma is to render a patient free of disease as long as the disease is sufficiently limited. When this is no longer feasible, intralesional therapy is a possible option due to its good local response and tolerable adverse-event profile, as well as the option to provide outpatient treatment. A bystander effect observed in various agents adds to its appeal. During the last few decades, other agents have been tested for intralesional therapy with varying success. Many intralesional compounds now available produce a broad range of local response rates. The ideal agent should have a low toxicity profile, be easy to administer, lead to fast responses, and trigger a systemic immune response, thereby creating a bystander effect. These criteria were predominantly met in the results of trials using 10% rose bengal and talimogene laherparepvec in up to 40% of study patients.
Most agents (Bacille-Calmette-Guerin, interferon, granulocyte macrophage colony-stimulating factor) demonstrated inconsistent rates of efficacy, but the treatment field changed when velimogene aliplasmid, 10% rose bengal, and talimogene laherparepvec were introduced. Velimogene aliplasmid did not meet its primary end point in a phase 3 trial, but talimogene laherparepvec did meet its phase 3 trial objectives, demonstrating a survival benefit in select study patients. The results of phase 2 results of 10% rose bengal trials are also promising and a phase 3 is still recruiting (NCT02288897). Other options include combinations of intralesional therapies and systemic therapies, including ipilimumab/talimogene laherparepvec and pembrolizumab/rose bengal (NCT02557321).
Our treatment approach should be individualized per patient, based on the extent of disease, tumor characteristics, and disease-free interval, as well as patient characteristics such as age, performance status, and comorbidities, and work to maintain quality of life for as long as possible. An appropriate approach is often not a single therapy but rather a combination of injectable treatments, regional perfusion therapies, and systemic therapies.
References
1. American Cancer Society. Cancer Facts & Figures 2016. Atlanta, GA: American Cancer Society; 2016. http://www.cancer.org/acs/groups/content/@ research/documents/document/acspc-047079.pdf. Accessed January 22, 2016.
2. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19(16):3635-3648.
3. Abbott AM, Zager JS. Locoregional therapies in melanoma. Surg Clin North Am. 2014;94(5):1003-15, viii.
4. Sanki A, Kam PC, Thompson JF. Long-term results of hyperthermic, isolated limb perfusion for melanoma: a reflection of tumor biology. Ann Surg. 2007;245(4):591-596.
5. Chai CY, Deneve JL, Beasley GM, et al. A multi-institutional experience of repeat regional chemotherapy for recurrent melanoma of extremities. Ann Surg Oncol. 2012;19(5):1637-1643.
6. Erickson C, Miller SJ. Treatment options in melanoma in situ: topical and radiation therapy, excision and Mohs surgery. Int J Dermatol. 2010;49(5):482-491.
7. TestoriA,FariesMB,ThompsonJF,etal.Localandintralesionaltherapy of in-transit melanoma metastases. J Surg Oncol. 2011;104(4):391-396.
8. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma. v2.2016. http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed January 22, 2016.
9. HerseyP,GallagherS.Intralesionalimmunotherapyformelanoma. J Surg Oncol. 2014;109(4):320-326.
10. Coley WB. The treatment of malignant tumors by repeated innoculations of erysipelas: with a report of ten original cases. 1893. Clin Orthop Relat Res. 1991;(262):3-11.
11. Handley WS. The pathology of melanotic growths in relation to their operative treatment. Lancet. 1907;i:927-33, 96-1003.
12. Sarnaik A, Crago G, Liu H, et al. Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions (abstract). J Clin Oncol. 2014;32(5 suppl):9028.
13. RossMI.IntralesionaltherapywithPV-10(rosebengal)forin-transit melanoma. J Surg Oncol. 2014;109(4):314-319.
14. Andtbacka,DelmanK.Responsesofinjectedanduninjectedlesions to intralesional tal-imogene laherparepvec (T-VEC) in the OPTiM study and the contribution of surgery to response. Presented at: Society of Surgical Oncology Cancer Symposium; Phoenix, Arizona; March 12–15, 2014. Abstract 52.
15. Sloot S, Rashid OM, Zager JS. Intralesional therapy for metastatic melanoma. Expert Opin Pharmacother. 2014;15(18):2629-639.
16. Bedikian AY, Richards J, Kharkevitch D, et al. A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma. Melanoma Res. 2010;20(3):218-226.
17. GreenDS,Bodman-SmithMD,DalgleishAG,etal.PhaseI/IIstudyof topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br J Dermatol. 2007;156(2):337-345.
18. Weide B, Derhovanessian E, Pflugfelder A, et al. High response rate after intratumoral treatment with interleukin-2: results from a phase 2 study in 51 patients with metastasized melanoma. Cancer. 2010;116(17):4139-4146.
19. Stopeck AT, Jones A, Hersh EM, et al. Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with metastatic melanoma. Clin Cancer Res. 2001;7(8):2285-2291.
