Sistemsko zdravljenje melanoma Systemic treatment of melanoma

Abstract

Melanom, če je odkrit dovolj zgodaj, je ozdravljiva bolezen, medtem ko v bolj napredovalih stadijih ostaja neozdravljiv. Kirurgija je še vedno osnovni način zdravljenja za lokalno, regionalno in izolirano metastatsko bolezen. Tveganje bolnikov z melanomom, debelejšim od 4 mm, za ponovitev bolezni je 50 %, bolnikov z zajetimi bezgavkami pa 50 do 85 % in je odvisno od števila zajetih bezgavk. Za to, da bi zmanjšali število ponovitev bolezni pri bolnikih z melanomom z velikim tveganjem, jih adjuvantno zdravimo z interferonom α (IFN α). IFN α je učinkovit, če ga uporabimo v visokih odmerkih. Tako zdravljeni bolniki imajo manj ponovitev bolezni in izboljšano 5-letno celokupno preživetje za 24 %. Zdravljenje ima tudi neželene učinke, ki pa so obvladljivi. Ostala zdravila v adjuvantnem zdravljenju niso toliko učinkovita, da bi značilno vplivala na preživetje. Metastatski melanom je neozdravljiva bolezen, kljub zdravljenju je preživetje bolnikov kratko. Različne sheme s kombinacijo tako citostatikov samih kot kombinacije citostatikov z imunoterapijo so dale več odgovorov na zdravljenje kot citostatiki v monoterapiji, vendar pa niso podaljšale preživetja teh bolnikov, več je bilo tudi neželenih učinkov. Tako citostatik dakarbazin v monoterapiji ostaja standardna kemoterapija zdravljenja bolnikov z metastatskim melanomom. V zadnjih letih je bilo v kliničnih raziskavah preizkušenih več novih tarčnih zdravil in imunoterapije. Klinično učinkovitost v podaljšanju časa do napredovanja bolezni in celokupnem preživetju sta izkazala ipilimumab in vemurafenib. V teku pa je še več raziskav o učinkovitosti različnih tarčnih zdravil, protiteles in najrazličnejših njihovih kombinacijah.

Abstract (Eng)

Melanoma is a curable disease if detected early, but in its advanced stages, it remains incurable. Surgery is still the primary treatment for local, regional and isolated metastatic disease. The risk for disease recurrence is 50% in patients with melanoma thicker than 4 mm and 50-85% in patients with lymph node involvement, depending on the number of the involved lymph nodes. To reduce the number of disease recurrences in high-risk melanoma patients, they are treated adjuvantly with interferon-α (IFN-α). The IFN-α is effective if used in high doses. Patients undergoing such treatment are less likely to experience disease recurrence and their 5-year overall survival rate has improved by 24%. Treatment also has adverse effects that are controllable. Other medicines used in adjuvant treatment are not effective enough to significantly impact patients' survival. Metastatic melanoma is an incurable disease and patient survival is short despite treatment. Different schemes, in combination with either cytostatics alone or cytostatics with immunotherapy, induced more responses to treatment than monotherapy with cytostatics. However, they failed to prolong the survival of these patients, and resulted in a higher incidence of adverse effects. Monotherapy with the cytostatic dacarbazine thus remains the standard chemotherapy for treatment of patients with metastatic melanoma. In the last few years, clinical trials tested several new target drugs and immunotherapy. Ipilimumab and vemurafenib showed clinical effectiveness in terms of prolonging the time to disease progression and overall survival. Moreover, there are also several ongoing studies examining the effectiveness of different target drugs, antibodies and various combinations thereof.