Colorectal cancer is one of the most common malignant tumors. In China, the incidence of colorectal cancer is ranked 4th and 3rd among men and women, respectively. Entering a state of advanced disease, the treatment strategy for these patients is chemotherapy-based comprehensive treatment. Compared with the best supportive treatment, it can significantly prolong the survival period and improve the quality of life. In the past two years, with the deepening of cancer molecular targeting research, the efficacy of targeted drugs is getting better and better, and the side effects are small, so that clinicians and patients have more treatment options. Let us take a look at the colorectal What are the current medication options for cancer?
Kolorektal saraton kasalligini davolash rejasi
(1) It is recommended to detect the gene status of shish K-ras, N-ras and BRAF before treatment, and EGFR is not recommended as a routine test item.
(2) Combined chemotherapy should be used as the first- and second-line treatment for patients with metastatic kolorektal saraton that can tolerate chemotherapy. The following chemotherapy regimens are recommended: FOLFOX or FOLFIRI, or combined with cetuximab (recommended for patients with wild-type K-ras, N-ras, BRAF genes), CapeOx, FOLFOX or FOLFIRI, or combined with bevasizumab.
(3) Patients with more than third-line chemotherapy are recommended to try targeted drugs or participate in clinical trials. For patients who do not use targeted drugs in first- and second-line therapy, irinotecan combined with targeted drug therapy can also be considered.
(4) Regofinil yoki klinik tadqiqotlar uchinchi darajali va undan yuqori standart tizim davolashda muvaffaqiyatsiz bo'lgan bemorlarga tavsiya etiladi. Birinchi va ikkinchi darajali davolanishda maqsadli dorilarni ishlatmaydigan bemorlar uchun irinotekan setuximab bilan birgalikda (yovvoyi turdagi K-ras, N-ras, BRAF genlari uchun tavsiya etiladi) ko'rib chiqilishi mumkin.
(5) Kombinatsiyalangan kimyoviy davolanishga toqat qilmaydigan bemorlar uchun ftorurasil + kaltsiy folinat sxemasi yoki kapesitabinli bitta dori yoki kombinatsiyalangan maqsadli dorilar tavsiya etiladi. Ftorurasil + kaltsiy leykovorin rejimiga mos kelmaydigan rivojlangan kolorektal saraton kasalligi bo'lgan bemorlar raltrekson bilan bitta agentli davolanishni ko'rib chiqishlari mumkin.
(6) Kasalligi 4 oydan 6 oygacha bo'lgan palliativ davolanishdan so'ng barqaror bo'lgan, ammo hali ham R0 rezektsiya qilish imkoniyati bo'lmagan bemorlar parvarishlash muolajasiga kirishni o'ylashlari mumkin (kam zaharli ftorurasil + kaltsiy leykovorin yoki kapesitabinli bitta dori kombinatsiyalangan maqsadli davolash, yoki tizimli tizimni davolashni to'xtatib turish) estrodiol kimyoviy terapiyaning toksikligini kamaytirish uchun.
(7) BRAF geni V600E mutatsiyasiga ega bemorlar uchun, agar umumiy holat yaxshiroq bo'lsa, FOLFOXIRI yoki bevacizumab bilan birgalikda birinchi darajali terapiya ko'rib chiqilishi mumkin.
(8) Agar rivojlangan bemorlarda umumiy holat yoki organ faoliyati juda yomon bo'lsa, eng yaxshi qo'llab-quvvatlovchi davolash tavsiya etiladi.
(9) Agar metastaz jigar va / yoki o'pka bilan chegaralangan bo'lsa, jigar metastazini va o'pka metastazini davolash tamoyillariga murojaat qiling.
(10) For patients with local recurrence of colorectal cancer, a multidisciplinary assessment is recommended to determine whether they have the opportunity to be resected or radiotherapy again. If it is only suitable for chemotherapy, the above principles of drug treatment for advanced patients are adopted.
Kolorektal saraton kasalligi bo'lgan bemorlar uchun kimyoviy terapiyani tanlash
Hozirgi vaqtda rivojlangan kolorektal saraton kasalligini davolash uchun ishlatiladigan kimyoviy terapiya preparatlariga quyidagilar kiradi: fluorourasil (shu jumladan og'iz orqali)
Kapesitabin), oksaliplatin va irinotekan.
bir
Induksion terapiya
1. Uchta dori rejasi
FOLFOXIRI [23]: irinotekan 165 mg / m2, vena ichiga infuziya, d1; oksaliplatin 85 mg / m2, tomir ichiga yuborish, d1; LV 400 mg / m2, tomir ichiga infuzion, d1; Birinchi kundan boshlab 5-FU 1 600 mg / (m2 · d) × 2 d doimiy vena ichiga infuziya (jami 3 200 mg / m2, 48 soat davomida infuziya). Har 2 haftada takrorlang.
2. Ikkala dori rejimi
(1) Oxaliplatin-based programs, such as FOLFOX and CapeOx, see the adjuvant treatment of yo'g'on ichak saratoni.
(2) Irinotekan asosidagi rejim: FOLFIRI: irinotekan 180 mg / m2, tomir ichiga 2 soat davomida quyish, d1; LV 400 mg / m2, tomir ichiga 2 soat davomida quyish, d1; 5-FU 400 mg / m2, vena ichiga bolus yuborish, d1, so'ngra 2 400 mg / m2, 46 dan 48 soatgacha tomir ichiga doimiy infuziya. Har 2 haftada takrorlang.
3. Yagona dori rejimi
Agar bemor kuchli dastlabki davolanishga toqat qilmasa, 5-FU / LV yoki kapesitabin infuzioni (aniq tafsilotlar uchun yordamchi terapiyani ko'ring) yoki bitta agentli irinotekan (125 mg / m2 irinotekan, tomir ichiga yuborish 30 ~ 90 minut, d1, d8, takroriy yoki har 3 haftada; yoki irinotekan 300-350 mg / m2, tomir ichiga infuzion 30-90 minut, d1, har 3 haftada takrorlanadi). Yoki irinotekan 180 mg / m2, tomir ichiga 2 soat davomida quyiladi, d1, har 2 haftada takrorlanadi.
Yuqoridagi davolanishdan so'ng, agar bemorning umumiy ahvoli yaxshilanmagan bo'lsa, eng yaxshi qo'llab-quvvatlovchi davolanish kerak.
ikki
Xizmatni davolash
OPTIMOX1 sinovi shuni ko'rsatdiki, metastatik kolorektal saraton kasalligi bilan FOLFOXni birinchi darajali davolash sifatida olgan bemorlarda oksaliplatinning "to'xtab turing" strategiyasidan vaqti-vaqti bilan foydalanish neyrotoksikani kamaytirishi mumkin, ammo omon qolish ta'sir qilmaydi [26]. Shuning uchun, 3 oydan 6 oygacha bo'lgan CR / PR / SD kasalligi kabi ikki agentli kombinatsiyalangan kimyoviy terapiyadan so'ng, oksaliplatin yoki irinotekan ko'proq nojo'ya reaktsiyalar bilan to'xtatilishi mumkin va rejimdagi boshqa dori-darmonlarni davolash muolajalari davom ettiriladi. O'simta o'sguncha, progressiyasiz omon qolish muddati uzaytirilishi mumkin, ammo umumiy omon qolish foydasi aniq emas.
uch
Ikkinchi, uchinchi va keyingi kimyoviy terapiya imkoniyatlari
Ikkinchi qatorli kimyoviy terapiyani tanlash birinchi navbatda davolash rejasiga bog'liq. Oksaliplatin va irinotekan asosidagi dasturlar bir-birining birinchi va ikkinchi qatori bo'lishi mumkin. Bemorning jismoniy holatiga ko'ra, bitta dori yoki kombinatsiyalangan davolash rejasini tanlang.
Uchinchi qatordan ko'proq kimyoviy terapiya bilan og'rigan bemorlarga maqsadli dori-darmonlarni sinab ko'rish yoki klinik sinovlarda qatnashish tavsiya etiladi. Birinchi va ikkinchi darajali terapiyada maqsadli dorilarni ishlatmaydigan bemorlar uchun irinotekanni maqsadli dori terapiyasi bilan birgalikda ko'rib chiqish mumkin.
Kolorektal saraton kasalligini maqsadli davolash
Maqsadli va immunoterapiya kolorektal saraton kasalligi uchun hozirgacha uyda va chet elda tasdiqlangan dorilar.
1. Bevatsizumab
Umumiy ism: Vey Ting
Inglizcha nomi: Avastin
Molekulyar tuzilish nomi: Bevacizumab
Asosiy ko'rsatkichlar: kolorektal saraton
Kelib chiqishi: Roche
Bevatsizumab (Avastin®) - bu rekombinant insoniylashtirilgan monoklonal antikor. U 26 yil 2004 fevralda FDA tomonidan ma'qullangan va bu o'sma angiogenezini bostiruvchi Qo'shma Shtatlarda tasdiqlangan birinchi dori edi.
Bevacizumabning bitta agent sifatida samaradorligi past va uni odatda kimyoviy terapiya bilan birgalikda qo'llash tavsiya etiladi.
Kombinatsiyalangan kimyoviy terapiya rejimi: IFL, FOLFIRI, FOLFOX va CapeOX; ishlatiladigan dozalar: 5 mg / kg (2 haftalik rejim) va 7.5 mg / kg (3 haftalik rejim).
Rivojlangan kolorektal saraton kasalligini davolashda IFL va bevacizumab kombinatsiyasi operatsion tizimni 15.6 oydan 20.3 oygacha oshirdi (AVF2107 tadqiqot).
Bevacizumab combined with FOLFIRI regimen as first-line treatment, the effective rate was 58.7%, PFS was 10.3 months (FIRE3 study).
Bevacizumab FOLFOX yoki FOLFIRI bilan birinchi qatorda davolanadi, PFS 11.3 oyga, operatsion tizim 31.2 oyga yetdi (CALGB80405 o'rganish).
2. Setuksimab
Umumiy ism: Erbitux
Inglizcha nomi: INFUSION UChUN CETUXIMAB SOLUTION
Molekulyar tuzilish nomi: Cetuximab
Asosiy ko'rsatkichlar: kolorektal saraton
Kelib chiqish joyi: Merkelion, Germaniya
Tsetuximab bilan davolashdan oldin, RAS geni barcha yovvoyi tipdagi bemorlarga ketuximabni ishlatishdan oldin tekshirilishi kerak. Cetuximabning samarali darajasi atigi 20% ni tashkil qiladi va odatda uni kimyoviy terapiya bilan birgalikda qo'llash tavsiya etiladi.
FOLFIRI va FOLFOX; dozasi: birinchi dozadan keyin haftasiga 400 mg / m2 250 mg / m2.
RAS yovvoyi tipidagi bemorlarda ketuximab FOLFIRI rejimi yoki FOLFOX sxemasi bilan qo'shilib, faqat kimyoterapiyaga qaraganda ancha uzoq PFS va operatsion tizimni keltirib chiqaradi.
3. Regafini
Umumiy ism: Baivango
Inglizcha nomi: regorafenib
Molekulyar tuzilish nomi: Regefenib
Asosiy ko'rsatkichlar: metastatik kolorektal saraton
Ishlab chiqarilgan joy: Bayer korporatsiyasi
Tegishli odamlar: 2012 yil sentyabr oyida Regefini FDA tomonidan yo'g'on ichak saratonini davolash uchun tasdiqlangan. 2017 yil may oyida Xitoyning CFDA tomonidan fluorourasil, oksaliplatin va irinotekan asosidagi kimyoviy terapiya va anti-VEGF terapiyasini davolash uchun regorafenib tasdiqlandi.
4. Panitumumab (panitumumab)
Umumiy ism: Viktibi
Inglizcha nomi: Erbitux cetuximab
Molekulyar tuzilish nomi: panitumumab
Asosiy ko'rsatkichlar: metastatik kolorektal saraton
Kelib chiqish joyi: amerikalik Amgen
Colorectal cancer treatment drugs Vectibix (panitumumab) and panitumumab are the first fully humanized monoclonal antibodies that target the epidermal growth factor receptor (EGFR). In July 2005, Panitumumab received FDA fast track approval. At the end of 2005, Amgen and its partner Abgenix jointly submitted a license application for this product to the FDA for the treatment of metastatic colorectal cancer after chemotherapy failure.
5. Ziv-aflibertsept (Abercept)
Inglizcha nomi: Zaltrap (infuziya uchun eritma uchun ziv-aflibercept)
Molekulyar tuzilish nomi: Abecip
Asosiy ko'rsatkichlar: metastatik kolorektal saraton
Kelib chiqishi: Sanofi
Abecip 2012 yilda rivojlangan kolorektal saraton kasalligini davolash uchun AQSh FDA tomonidan ma'qullangan. Bu inson qon tomirlari endotelial o'sish omilini inhibe qilish orqali o'smaning ozuqaviy moddalarini etkazib berishni cheklaydigan va shu bilan o'smaning ko'payishini inhibe qiluvchi ximerik protein preparati.
Aflibercept tanadagi aylanadigan VEGF bilan bog'lanib, "VEGF tuzog'i" kabi harakat qiladi. Shuning uchun ular qon tomir endotelial o'sish omillari navbati bilan VEGF-A va VEGF-B va platsenta o'sish faktori (PGF) faoliyatini inhibe qiladi va chorionik kistalarda yoki o'smalarda yangi qon tomirlarining o'sishini inhibe qiladi. Aytish mumkinki, Aflibertseptning maqsadi o'simta to'qimasini "och qoldirish".
6. Ramolimumab (Cyramza)
Inglizcha nomi: ramucirumab
Molekulyar tuzilish nomi: Remolumumab
Asosiy ko'rsatkichlar: kolorektal saraton
Kelib chiqishi: Eli Lilly va Company
Cyramza was approved by the US FDA in 2014 to treat gastric cancer, colorectal cancer and non-small cell lung saraton.
O'simta to'qimasi kattalashganda u angiogenez jarayonini boshdan kechiradi, ya'ni o'simta hujayralariga ozuqa moddalarini tashish uchun o'sma to'qimasi atrofida yangi qon tomirlari hosil bo'ladi. Shuning uchun bu jarayonni inhibe qilish aksariyat o'smalarning ko'payishini inhibe qilishi mumkin.
Cyramza - bu monoklonal antikor dori, asosan o'smaning atrofida yangi qon tomirlarining paydo bo'lishini inhibe qiladi va qon tomirlari endoteliy o'sish faktori retseptorlari (VEGFR2) bilan bog'lanib o'smaning ozuqa moddalarini etkazib berishini inhibe qiladi va shu bilan o'smaning ko'payishini inhibe qiladi.
7. Frukintinib
Mahsulot nomi: Aiyoute
Qo'llanilishi mumkin bo'lgan alomatlar: Xitoyda 5-sentabrda avvalgi florurasil, oksaliplatin va irinotekan asosidagi kimyoviy terapiyani davolash, shuningdek qon tomirlarga qarshi endotelial o'sish omili (VEGF) bilan oldingi yoki yaroqsiz davolanish uchun ma'qullangan 1. Metastatik CRC bilan kasallangan bemorlarga anti- epidermal o'sish omil retseptorlari (EGFR) (RAS yovvoyi turi).
7. opdivo
Inglizcha nomi: nivolumab
Molekulyar tuzilish nomi: nivolumab
Asosiy ko'rsatkichlar: kolorektal saraton
Place of Origin: Bristol-Myers Squibb
Ono and Bristol Myers Squibb (BMS) joint research and development, in July 2014 by the Japanese Pharmaceutical and Medical Devices Agency (PMDA) approval, December 2014 by the US Food and Drug Administration (FDA) Approved, approved by the European Medicines Agency (EMA) in June 2015, approved by the China Food and Drug Administration (CFDA) for marketing in June 2018, and sold by Ono Pharmaceuticals in Japan, Bristol-Myers Squibb in the United States, It is sold in Europe and China under the brand name Odivo®.
Kolorektal saraton kasalligining so'nggi davolash jarayoni
1) TAS-102 (Lonsurf)
TAS102 is an oral chemotherapeutic drug composed of the anti-tumor nucleoside analog FTD (trifluorothymidine, trifluridine) and thymidine phosphorylase inhibitor TPI.
TAS102 + bevacizumab bilan davolangan TT-B guruhining mPFS 9.2 oyni tashkil etdi, bu an'anaviy davolash qilingan kapesitabin + bevacizumab CB guruhining 7.8 oyiga nisbatan ancha yuqori. Progressiyasiz omon qolish. Bunday bemorlarni davolashning yangi birinchi usuli bo'lishi kutilmoqda.
2) Uchta dori kombinatsiyasida kashfiyot terapiyasining afzalliklari nimada?
Birlashtirish enkorafenib, binimetinib and cetuximab for BRAF mutation patients is a big change, because multiple studies have shown that the combination of BRAF inhibitors and MEK inhibitors in refractory patients, It can be seen that the reaction rate exceeds 30%, which is unheard of.
Yaqinda 2018 yilda oshqozon-ichak saratonining Butunjahon Kongressida taqdim etilgan ma'lumotlar shuni ko'rsatadiki, uchta dori kombinatsiyasi nafaqat yuqori javob berish darajasiga ega, balki uzoq muddatli PFS va OSga ham ega. Shuning uchun birinchi darajali terapiyada sinovlar ishlab chiqilmoqda. Qizig'i shundaki, ushbu uchlik sitotoksik maqsadli dorilarni o'z ichiga olmaydi. Bu shuni ko'rsatadiki, u o'sma molekulalarini oqilona aniqlay oladi va juda ko'p toksiklik tug'dirmasdan muhim klinik ta'sirlarni keltirib chiqaradi.
3) Immunoterapiyaning rivojlanishi qanday?
MSI-H o'smalari uchun nivolumab va ipilimumab kombinatsiyasi birinchi darajali davolanishni olish imkoniyatiga ega, chunki samaradorlik ma'lumotlari juda ishonchli ko'rinadi.
Mikrosatellitning barqaror o'smalari uchun biz immunoterapiyani standart kimyoterapiya-FOLFOX / bevacizumab bilan nivolumab bilan birlashtirishimiz kerak.
