Akci\u011fer Kanseri 20. Y\u00fczy\u0131l\u0131n en \u00f6nemli hastal\u0131klar\u0131ndan biri olarak d\u00fcnya tarihine ge\u00e7ti. Bu hastal\u0131\u011f\u0131n en \u00f6nemli nedeninin sigara oldu\u011fu gerek istatistiki olarak gerek biyolojik olarak ispatland\u0131. Bat\u0131 \u00fclkelerinde sigaray\u0131 b\u0131rakma e\u011filimlerini takiben akci\u011fer kanseri vakalar\u0131n\u0131n g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131nda, en az\u0131ndan erkeklerde bir azalma e\u011filimi belirdi. Kad\u0131nlarda akci\u011fer kanserinden \u00f6l\u00fcmler meme kanseri \u00f6l\u00fcmlerini say\u0131ca a\u015ft\u0131. Ge\u00e7ti\u011fimiz y\u0131l d\u00fcnyada yar\u0131m milyonu a\u015fk\u0131n insan akci\u011fer kanseri ile te\u015fhis edildi ve ne yaz\u0131k ki bu insanlar\u0131n \u00e7ok \u00f6nemli bir b\u00f6l\u00fcm\u00fc (tahminen %85i) bu hastal\u0131ktan vefat etti.<\/p>\n
Until the 1960s, lung cancer was considered a homogenous disease, but it has since become clear that there are two main types: small cell and non-small cell.<\/p>\n
Small cell lung cancer was found to be biologically different from other lung cancers, and its treatment has been systemic chemotherapy since the 1970s. Small cell lung cancers are divided into two groups. In the limited stage, the disease is present in the chest cavity, lungs, and lymph nodes. In the extensive stage, the disease has spread to other organs in the body via the bloodstream. One of the most important characteristics of this disease is its tendency to metastasize to the brain.<\/p>\n
S\u0131n\u0131rl\u0131 evrede en iyi tedavi kemoterapi ve radyoterapidir. \u0130deali hastay\u0131 hem kemoterapi hem radyoterapi ile e\u015f zamanl\u0131 tedavi etmektir (radyoterapi kemoterapinin ba\u015flang\u0131c\u0131ndan itibaren ilk 6-9 haftada tedaviye kat\u0131l\u0131rsa en y\u00fcksek iyile\u015fme oran\u0131 saptan\u0131r ki bu %25 civar\u0131ndad\u0131r). Ancak e\u015f zamanl\u0131 kemoterapi ve radyoterapinin yan etkileri olduk\u00e7a fazla ve hatta hayati tehlike yarat\u0131r \u015fekilde olabilir. Bu nedenle e\u015f zamanl\u0131 tedavi alacak hastalar\u0131 iyi se\u00e7mek ve bu durumu hasta ile ayr\u0131nt\u0131l\u0131 konu\u015fmak gerekir. E\u015f zamanl\u0131 tedavi uygulanmasa da kemoterapiyi takiben yap\u0131lacak radyoterapi ile hastalar\u0131n bir b\u00f6l\u00fcm\u00fc iyile\u015febilir. S\u0131n\u0131rl\u0131 evrede tercih edilen kemoterapi cisplatin ve etoposidedir. Yirmibir g\u00fcnde bir \u00fc\u00e7 g\u00fcn s\u00fcreyle uygulan\u0131r. Cisplatin uygulamas\u0131nda hastaya intraven\u00f6z olarak bol s\u0131v\u0131 vermek ve idrar \u00e7\u0131k\u0131\u015f\u0131n\u0131 takip etmek \u00f6nemlidir. Bu tedavinin en \u00f6nemli yan etkilerinden olan bulant\u0131y\u0131 tedavi i\u00e7in antiemetik ila\u00e7lar (ilk 24 saatte ondansetron, granisetron, d\u00f6rt g\u00fcn s\u00fcreyle metoclopromide ve lorazepam kombinasyonu pop\u00fcler bir tercihtir) kullan\u0131lmal\u0131d\u0131r. Toplam 4 k\u00fcr yeterlidir. Tedavi bitimini takiben hastay\u0131 d\u00fczenli bir \u015fekilde bilgisayarl\u0131 tomografi (BT) ile takip etmekte yarar vard\u0131r. Hastal\u0131k geri gelirse yayg\u0131n evrede kullan\u0131lan ila\u00e7larla ya\u015fam kalitesini d\u00fczeltmek ve s\u00fcreyi uzatmak m\u00fcmk\u00fcn olur.<\/p>\n
In the advanced stage, the primary treatment is chemotherapy. Platinum (cisplatin or carboplatin) and etoposide are used as standard treatments. In selected cases, adding immunotherapy to chemotherapy may positively influence the course of the disease. There is no evidence of benefit in administering more than 4 cycles of treatment, or in providing maintenance therapy after chemotherapy, or even in performing bone marrow transplantation. Irinotecan is the second-best choice when the disease progresses. If the patient's general condition is good, additional treatments may be tried. In this case, some patients may benefit from taxane group drugs (paclitaxel, docetaxel, and finally nab-paclitaxel). While the standard treatment for cases with cerebral metastasis is brain radiotherapy, in cases of small metastases and widespread systemic metastases, it may be possible to start treatment with chemotherapy and achieve a response to chemotherapy in brain metastases as well.<\/p>\n
K\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanserlerinin temel tedavisi cerrahidir. Tedaviyi belirlemede hastal\u0131\u011f\u0131n evresinin ameliyat \u00f6ncesinde saptanmas\u0131 \u00e7ok \u00f6nemlidir. Bu ama\u00e7la g\u00fcn\u00fcm\u00fczde her hastaya PET tomografi (PET-CT) ve beyin MR’\u0131 yap\u0131lmas\u0131 gerekir. Ancak (sigara i\u00e7en insanlar\u0131n senede bir spiral BT ile taranarak erken te\u015fhisi olamad\u0131\u011f\u0131 durumlarda) hastalar\u0131n ancak %30’u ameliyat olabilecek evrelerde (Evre I veya II) yakalan\u0131rlar. Hastal\u0131k g\u00f6\u011f\u00fcs orta bo\u015flu\u011fu (mediasten) i\u00e7indeki lenf bezlerine s\u0131\u00e7rad\u0131\u011f\u0131nda (Evre III), ameliyat\u0131n bir yarar\u0131 olmad\u0131\u011f\u0131 \u00e7e\u015fitli \u00e7al\u0131\u015fmalarda g\u00f6sterilmi\u015ftir. Bunun tek istisnas\u0131, tek bir mediastinal lenf bezinde mikroskobik bir metastaz\u0131n olmas\u0131 ve hastan\u0131n bir lobunun (lobektomi) al\u0131nmas\u0131 ile hastal\u0131\u011f\u0131n \u00e7\u0131karabildi\u011fi durumlard\u0131r. Bu nedenle, hastalar\u0131n esas operasyondan \u00f6nce mediastinoskopi (PET-CT sonu\u00e7lar\u0131 mediastende hastal\u0131k g\u00f6stermese de) denen ufak bir operasyon ge\u00e7irmeleri yoluyla mediastendeki lenf bezlerine hastal\u0131\u011f\u0131n atlay\u0131p atalamd\u0131\u011f\u0131 belirlenmelidir. Cerrah\u0131n se\u00e7imine ba\u011fl\u0131 olarak mediastinoskopi esas ameliyatla e\u015fzmanl\u0131 yap\u0131labilir. Bu durumda bir patoloji uzman\u0131 ameliyat esans\u0131nda frozen denen bir y\u00f6ntemle mediastendeki lenf bezlerinde kanser h\u00fccreleri olup olmad\u0131\u011f\u0131n\u0131 belirler. Mediastendeki birden fazla lenf bezinde kanser mevcutsa operasyona son verilir. Uzun y\u0131llar boyunca ameliyat edilemiyen k\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanserlerinin tedavisinde kemoterapi ila\u00e7lar\u0131 kullan\u0131lmad\u0131 ve bu hastalar son \u00e7are olarak palyatif radyoterapi ile tedavi edildiler.<\/p>\n
Bu yaz\u0131n\u0131n ana konusunu k\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanserlerinde yeni kemoterapi ila\u00e7lar\u0131n\u0131n uygulanmas\u0131 olu\u015fturuyor. Bu hastalar\u0131n %30’u ameliyat olabilecek evrelerde (Evre I ve II) te\u015fhis edilir. T\u00fcm hastalar\u0131n %90’\u0131 ise hastal\u0131klar\u0131n\u0131n bir d\u00f6neminde yeni kemoterapi ila\u00e7lar\u0131ndan yararlanma ihtiyac\u0131nda olacaklar (sistemik metastazlar veya lokal n\u00fcksler dolay\u0131s\u0131yla). Son y\u0131llara kadar kemoterapi ila\u00e7lar\u0131n\u0131n bu hastalar\u0131n tedavisinde bir rol\u00fc olmad\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fcl\u00fcrd\u00fc. Cisplatin’in 1970’li y\u0131llarda ke\u015ffinden sonra bu ilac\u0131n k\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanserinde o zamana kadar bilinen ila\u00e7lardan daha etkili oldu\u011fu g\u00f6r\u00fcld\u00fc. Uzun s\u00fcren randomize \u00e7al\u0131\u015fmalar sonucunda cisplatin i\u00e7eren kemoterapi tedavilerinin hastalar\u0131n \u00f6mr\u00fcn\u00fc uzatt\u0131\u011f\u0131 ve hayat kalitesini artt\u0131rd\u0131\u011f\u0131 ispat edildi. Cisplatin i\u00e7eren kemoterapi sayesinde bir y\u0131lda hayatta kalan k\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanserli hasta say\u0131s\u0131 iki misli artt\u0131 ve tedaviye objektif cevap vermeyen hastalarda bile kemoterapi ile hastal\u0131\u011fa ait semptomlar\u0131n azald\u0131\u011f\u0131 ve hastan\u0131n ya\u015fam kalitesinin artt\u0131\u011f\u0131 g\u00f6sterildi.<\/p>\n
From today onwards, all patients with non-small cell lung cancer (Stage III and IV) who would not benefit from surgery should be considered candidates for chemotherapy.<\/p>\n
Chemotherapy can be used in three important ways in these patients:
\n1. As a neoadjuvant, meaning after diagnosis and before local treatments.
\n2. As an important part of combined treatment with radiotherapy in locally advanced cancers.
\n3. In metastatic cases, with the aim of both prolonging life and improving quality of life.<\/p>\n
In chemotherapy treatments containing cisplatin, the most significant problem used to be treatment-related nausea and vomiting. Today, thanks to various supportive medications in the serotonin antagonist group (Zofran, Kytril), such nausea is a thing of the past. In addition, the discovery of new drugs that are at least as effective as cisplatin and have fewer side effects has begun to dramatically change lung cancer treatment. Carboplatin, a second-generation sibling of cisplatin, is a drug that is both as effective as cisplatin and has virtually no nausea or kidney side effects.<\/p>\n
These drugs have increased the range of medication options available to patients with lung cancer, and in many cases, have made treatment more successful and less damaging in terms of side effects. Below, I will briefly discuss these drugs and their use in non-small cell lung cancer.<\/p>\n
Paclitaxel (Taxol) Paclitaxel akci\u011fer tedavisinde son y\u0131llarda bulunan en etkili ila\u00e7lardan biri. Pasifik okyanusu k\u0131y\u0131s\u0131nda bulunan bir a\u011fa\u00e7tan elde edilmekte. Bir k\u00fcr tedavi i\u00e7in ortalama \u00fc\u00e7 a\u011fac\u0131n kesilmesi gerekiyordu. \u015eimdi ileri teknoloji ile bu ila\u00e7 sentetik olarak do\u011fal formunun birebir ayn\u0131s\u0131 olarak imal edilebilmekte. Bu bak\u0131mdan ila\u00e7 olduk\u00e7a pahal\u0131. Ancak akci\u011fer kanserinde tek ba\u015f\u0131na bile kullan\u0131ld\u0131\u011f\u0131nda \u015fimdiye kadar bir ila\u00e7 i\u00e7in kaydedilmi\u015f en y\u00fcksek etkinli\u011fi g\u00f6steriyor. \u0130kinci az klinik \u00e7al\u0131\u015fmalarda paclitaxel alan metastatik k\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanserli hastalar\u0131n %40’\u0131n\u0131n bir sene sonunda hayatta oldu\u011fu g\u00f6sterildi. Kombine tedavide de paclitaxel \u00e7ok etkili. \u00d6zellikle carboplatin ile birlikte kullan\u0131ld\u0131\u011f\u0131nda hem yan etkileri ilgin\u00e7 bir bi\u00e7imde azal\u0131yor hem de metastatik hastalarda %50’nin \u00fcst\u00fcnde klinik cevap g\u00f6steriyor. Di\u011fer ila\u00e7larla kombine edildi\u011fi \u00e7al\u0131\u015fmalar s\u00fcrmekte. Paclitaxelin bir di\u011fer \u00f6zelli\u011fi ise radyoterapinin etkinli\u011fini artt\u0131rabilmesi. Docetaxel (Taxotere) Docetaxel paclitaxelin semi-sentetik t\u00fcrevi. Ayn\u0131 tipte bir a\u011fac\u0131n yapraklar\u0131ndan ek bir reaksiyon ile \u00fcretilmekte. Bu da olduk\u00e7a pahal\u0131 bir ila\u00e7. Ancak akrabas\u0131 paclitaxel gibi akci\u011fer kanseri tedavisinde \u015fimdiye kadar bulunmu\u015f en etkili ila\u00e7lardan biri. Evre III ve IV k\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanserli hastalarda cevap oran\u0131 %35’lerde ve bir y\u0131ll\u0131k survi %40 civar\u0131nda. \u00d6zellikle cisplatine cevap vermemi\u015f hastalarda hi\u00e7 tedavi olmam\u0131\u015f hastalarda oldu\u011fu kadar etkili olmas\u0131 b\u00fcy\u00fck bir avantaj. Profilaktik steroid kullan\u0131m\u0131 sayesinde en korkulan \u00f6dem yan etkisi de yok denecek kadar az oluyor. Son zamanlarda haftada bir az dozda kullan\u0131lmas\u0131n\u0131n da hem etkinlik a\u00e7\u0131s\u0131ndan ayn\u0131 oldu\u011fu hem de yan etkiler a\u00e7\u0131s\u0131ndan (sa\u00e7 d\u00f6k\u00fclmesi ve n\u00f6tropeni) daha hafif oldu\u011fu g\u00f6zlendi. \u015eimdilik genellikle tek ba\u015f\u0131na kullan\u0131lmakta ancak kombine kullan\u0131m\u0131na ait klinik \u00e7al\u0131\u015fmalar da s\u00fcrmekte.<\/p>\n
Gemcitabine (Gemzar) Bir sentetik pyrimidine nucleoside analogu olan Gemcitabine bir\u00e7ok solid t\u00fcm\u00f6r (akci\u011fer. pankreas, mesane, meme) tedavisinde \u00f6nemli bir rol oynamaya ba\u015flad\u0131. En \u00f6nemli kullan\u0131m sahas\u0131 ise k\u00fc\u00e7\u00fck h\u00fccreli d\u0131\u015f\u0131 akci\u011fer kanseri olacak gibi g\u00f6z\u00fck\u00fcyor. D\u00f6rty\u00fcz\u00fc a\u015fk\u0131n akci\u011fer kanserli hasta \u00fczerinde yap\u0131lan \u00e7al\u0131\u015fmalarda Gemcitabine ile %21 klinik cevap ve 26-46 hafta median survi g\u00f6zlendi. Bunun yan\u0131nda hastalar\u0131n %60-70’inin ilac\u0131 ald\u0131ktan sonra klinik olarak daha iyi olduklar\u0131 ve semptomlar\u0131n\u0131n azald\u0131\u011f\u0131 g\u00f6r\u00fcld\u00fc. Gemcitabine’in en \u00f6nemli \u00f6zelli\u011fi yan etkilerinin olduk\u00e7a az olmas\u0131 (bulant\u0131 \u00e7ok nadir, sa\u00e7 d\u00f6k\u00fclmesi genellikle az ve kan say\u0131mlar\u0131 \u00fcst\u00fcne etkisi hafif) ve ilac\u0131n uygulanmas\u0131n\u0131n kolay olmas\u0131 (haftada bir 30 dakikal\u0131k IV infuzyon). Gemcitabine \u00f6zellikle cisplatin ile birlikte kullan\u0131ld\u0131\u011f\u0131nda etkisi artmakta (cisplatin ve gemcitabine %48 klinik cevap g\u00f6stermekte iken uzun y\u0131llar akci\u011fer kanserinde standart kombinasyon tedavi olarak kullan\u0131lan cisplatin ve etoposide ayn\u0131 hasta grubunda randomize \u00e7al\u0131\u015fmada %22 cevap g\u00f6sterdi). Di\u011fer ila\u00e7larla kombine tedavisi klinik \u00e7al\u0131\u015fma safhas\u0131nda s\u00fcrmektedir.<\/p>\n
Pemetrexed (Alimta) is successfully used, particularly in lung cancers of the adenocarcinoma type. It does not have the classic chemotherapy side effects such as hair loss, decreased blood counts, and nausea. It can be successfully used as a maintenance treatment alone for up to one year following the initial treatment period.<\/p>\n
Akci\u011fer kanserinde kullan\u0131lan ila\u00e7 say\u0131s\u0131 her ge\u00e7en g\u00fcn artmakta. Yukar\u0131da bahsetti\u011fim ila\u00e7lara ek olarak son y\u0131llarda \u00f6ne \u00e7\u0131kan bir tedavi y\u00f6ntemi mevcut. Immunoterapi denen bu y\u00f6ntemde T\u00fcm\u00f6rle sava\u015fan v\u00fccut h\u00fccrelerinin \u00fcst\u00fcndeki PD-1 veya t\u00fcm\u00f6r h\u00fccrelerinin PD-1\u2019e ba\u011flanmak i\u00e7in kulland\u0131klar\u0131 PDL-1 molek\u00fclleri hedef al\u0131n\u0131yor. \u015e\u00f6yle ki, t\u00fcm\u00f6r h\u00fccreleri zarlar\u0131ndaki PDL-1 ile ba\u011f\u0131\u015f\u0131kl\u0131k h\u00fccrelerinin PD-1 a\u011f\u0131zc\u0131\u011f\u0131na ba\u011flan\u0131yor ve ba\u011f\u0131\u015f\u0131kl\u0131k h\u00fccrelerini bir nevi uyutarak etkisiz hale getiriyor. E\u011fer ba\u011f\u0131\u015f\u0131kl\u0131k h\u00fccreleri \u00fcst\u00fcndeki PD-1 bir antikorla bloke edilirse bu h\u00fccreler kuvvetleniyor ve aktive olarak t\u00fcm\u00f6r h\u00fccrelerine sald\u0131rarak onlar\u0131 yok ediyorlar. \u0130lk olarak geli\u015ftirilen anti PD-1 antikorlar\u0131 Nivolumab (tic. \u0130smi Opdivo) ve Pembrolizumab (Tic. \u0130smi Keytruda), akci\u011fer kanserli hastalar\u0131n %15-50\u2019sinde yarar g\u00f6sterebiliyorlar. Hangi hastalarda daha yararl\u0131 olabildiklerine ili\u015fkin en \u00f6nemli g\u00f6sterge t\u00fcm\u00f6rdeki mutasyon y\u00fck\u00fc. Her megabase genetik materyelde 18\u2019den fazla mutasyon mevcutsa buna y\u00fcksek mutasyonal y\u00fck deniyor (yani t\u00fcm\u00f6rde \u00e7ok mutasyon var) ve bu \u015fimdiye kadarki en iyi g\u00f6sterge. Bunu tayin etmek i\u00e7in t\u00fcm\u00f6r blo\u011funun genomik analizinin yap\u0131lmas\u0131 gerekiyor. \u0130kinci \u00f6nemli g\u00f6sterge t\u00fcm\u00f6r dokusunda PDL-1 ekspresyonunun immunohistokimya y\u00f6ntemiyle saptanmas\u0131. Bu ekspresyon ne kadar y\u00fcksekse immunoterapi ila\u00e7lar\u0131n\u0131n \u00e7al\u0131\u015fma olas\u0131l\u0131\u011f\u0131 o denli y\u00fcksek oluyor.<\/p>\n
Immunoterapi ila\u00e7lar\u0131 halen akci\u011fer kanserlerinde Evre IV hastalar\u0131nda birinci ve ikinci kademede kemoterapi ila\u00e7lar\u0131 ile birlikte birinci kademede standart tedavi olarak kullan\u0131l\u0131yorlar. Bu ila\u00e7lar\u0131n avantajlar\u0131, e\u011fer hastal\u0131k bu ila\u00e7lara cevap verirse, cevap s\u00fcresi olduk\u00e7a uzun oluyor (ortalama bir bu\u00e7uk seneden uzun). \u0130la\u00e7lar\u0131n sa\u00e7 d\u00f6kme ve bulant\u0131 ve kan say\u0131mlar\u0131n\u0131 d\u00fc\u015f\u00fcrme gibi yan etkileri yok. Tam tersine ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 kuvvetlendirebiliyorlar. En ciddi yan etkisi de ba\u011f\u0131\u015f\u0131kl\u0131 h\u00fccrelerinin \u00e7ok kuvvetlenip aktive olup normal dokulara sald\u0131rmas\u0131. Olduk\u00e7a nadir g\u00f6r\u00fclen bu yan etki hastlar\u0131n %2-5\u2019inde ortaya \u00e7\u0131k\u0131yor ve imm\u00fcn pn\u00f6moni, kolit, tiroidit, veya hepatit \u015feklinde en s\u0131k ortaya \u00e7\u0131k\u0131yor. Kortizon tedavisi ile iyile\u015fme oran\u0131 %100\u2019e yak\u0131n oluyor.<\/p>\n
In the coming years, this group of immunotherapy drugs will find wider applications in the treatment of lung cancer.<\/p>\n
Now, as doctors, our duty is to know that treatment alternatives are available for this common and important disease in our country, and to follow important developments in this field so that our patients are not deprived of these opportunities.<\/p>","protected":false},"excerpt":{"rendered":"
Akci\u011fer Kanseri 20. Y\u00fczy\u0131l\u0131n en \u00f6nemli hastal\u0131klar\u0131ndan biri olarak d\u00fcnya tarihine ge\u00e7ti. Bu hastal\u0131\u011f\u0131n en \u00f6nemli nedeninin sigara oldu\u011fu gerek istatistiki olarak gerek biyolojik olarak ispatland\u0131. Bat\u0131 \u00fclkelerinde sigaray\u0131 b\u0131rakma e\u011filimlerini takiben akci\u011fer kanseri vakalar\u0131n\u0131n g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131nda, en az\u0131ndan erkeklerde bir azalma e\u011filimi belirdi. Kad\u0131nlarda akci\u011fer kanserinden \u00f6l\u00fcmler meme kanseri \u00f6l\u00fcmlerini say\u0131ca a\u015ft\u0131. Ge\u00e7ti\u011fimiz y\u0131l<\/p>","protected":false},"author":3,"featured_media":2667,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[518],"tags":[],"class_list":["post-2683","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-kanser-teshis-ve-tedavisi"],"yoast_head":"\n