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?
Colorectal cancer kurapwa chirongwa
(1) It is recommended to detect the gene status of tumarara 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 kenza yakajeka 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 bevacizumab.
(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 kana kiriniki miedzo inokurudzirwa kune varwere vakakundikana wechitatu-mutsara uye pamusoro peyakajairika system kurapwa. Kune varwere vasingashandisi yakanangana nemishonga mune yekutanga- uye yechipiri-mutsara kurapwa, irinotecan inosanganiswa necetuximab (yakakurudzirwa yemusango-mhando K-ras, N-ras, BRAF magene) anogona zvakare kutariswa.
(5) Kune varwere vasingakwanise kutsungirira chemotherapy yakasanganiswa, iyo fluorouracil + calcium folinate scheme kana capecitabine mushonga mumwe kana musanganiswa wakanangwa mishonga inokurudzirwa. Varwere vane yakakwira colorectal kenza avo vasina kukodzera iyo fluorouracil + calcium leucovorin regimen vanogona kufunga nezve imwechete-mumiririri kurapwa ne raltrexone.
(6) Varwere vane chirwere chakadzikama mushure memwedzi mina kusvika kumitanhatu yekurapa asi vasina mukana weR4 resection vanogona kufunga nezvekurapa kurapwa (sekushandiswa kwechishoma chepfu fluorouracil + calcium leucovorin, kana capecitabine mushonga mumwe chete wakasanganiswa kunongedzera Kurapa, kana kumisa systemic system kurapwa) kudzikisa huturu hweakasanganiswa chemotherapy.
(7) Kune varwere vane BRAF gene V600E mutation, kana iyo general mamiriro ari nani, FOLFOXIRI kana yekutanga-mutsara kurapwa pamwe nebevacizumab inogona kutariswa.
(8) Kana mamiriro akajairika kana basa renhengo rakashata kwazvo muvarwere vemberi, kurapa kwakanyanya kutsigira kunokurudzirwa.
(9) Kana iyo metastasis yakaganhurirwa kuchiropa uye / kana mapapu, tarisa kune ekurapa maitiro echiropa metastasis uye mapapu metastasis.
(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.
Sarudzo ye chemotherapy yevarwere vane colorectal cancer
Chemotherapy mishonga yazvino inoshandiswa kurapa yakakwira colorectal kenza inosanganisira: fluorouracil (kusanganisira muromo
Capecitabine), oxaliplatin uye irinotecan.
One
Induction kurapwa
1. Zvirongwa zvemishonga mitatu
FOLFOXIRI [23]: irinotecan 165 mg / m2, kupinza kumisidzana, d1; oxaliplatin 85 mg / m2, kumisirwa mukati meiyo intravenous, d1; LV 400 mg / m2, kumisikidzwa kwemukati, d1; 5-FU 1 600 mg / (m2 · d) × 2 d inoenderera inopinza kumisikidza (yakazara 3 200 mg / m2, kumisikidzwa kwemaawa makumi mana nemasere), kutanga pazuva rekutanga. Dzokorora vhiki mbiri dzese.
2. Dual regimen drug
(1) Oxaliplatin-based programs, such as FOLFOX and CapeOx, see the adjuvant treatment of kenza yemaroni.
(2) Irinotecan-based regimen: FOLFIRI: irinotecan 180 mg / m2, kupinza kumisidzana kwemaawa maviri, d2; LV 1 mg / m400, kumisikidzwa kwemukati kwemaawa maviri, d2; 2-FU 1 mg / m5, Intravenous bolus jekiseni, d400, uyezve 2 1 mg / m2, inoenderera inopinza intravenous kwema 400 kusvika kumaawa 2. Dzokorora vhiki mbiri dzese.
3. Imwe chete regimen regimen
Kana murwere asingakwanise kutsungirira kwakasimba kurapwa kwekutanga, 5-FU / LV kana capecitabine infusion (ona chinobatsira kurapwa kwemamwe marondedzero) kana iyo-mumiririri irinotecan (125 mg / m2 irinotecan, kupinza kupinza 30 ~ 90 maminetsi, d1, d8, yakadzokororwa vhiki nhatu dzese; kana irinotecan 3-300 mg / m350, inisation infusion 2-30 maminetsi, d90, inodzokororwa vhiki dzese dze1). Kana irinotecan 3 mg / m180, kumisikidzwa mukati meiyo maawa maviri, d2, ichidzokororwa vhiki mbiri dzese.
Mushure mekurapa pamusoro, kana mamiriro evarwere asina kuvandudzwa, kurapwa kwakanyanya kunofanira kupihwa.
Piri
Kuchengetedza kurapwa
Iko OPTIMOX1 kutongwa kwakaratidza kuti kune varwere vane metastatic colorectal cancer vanogamuchira FOLFOX sekutanga-kurapwa kurapwa, iko kupindirana kweiyo oxaliplatin's "mira uende" zano kunogona kudzora neurotoxicity asi haina kukanganisa Kupona [26]. Naizvozvo, mushure memwedzi mitatu kusvika kumitanhatu yeaviri-mumiririri wemubatanidzwa chemotherapy, senge chirwere CR / PR / SD, oxaliplatin kana irinotecan ine hutachiona hwakanyanya inogona kumiswa, uye mamwe marapirwo ekuchengetedza zvinodhaka muhurongwa anoenderera. Kusvikira bundu richifambira mberi, kufambira mberi-kwemahara kuponeswa kunogona kuwedzerwa, asi iyo yese yekupona kubatsirwa haina kuoneka.
Tatu
Chechipiri, chechitatu uye chinotevera chemotherapy sarudzo
Sarudzo yechipiri-mutsara chemotherapy inoenderana neyekutanga-tambo yekurapa chirongwa. Iyo oxaliplatin-based uye irinotecan-based zvirongwa zvinogona kuve yekutanga uye yechipiri mutsara weumwe neumwe. Zvinoenderana nemamiriro emurwere, sarudza mushonga mumwe kana chirongwa chekubatanidza.
Varwere vane inopfuura yetatu-mutsara chemotherapy vanokurudzirwa kuyedza yakanangwa zvinodhaka kana kutora chikamu mumakiriniki ekuedzwa. Kune varwere vasingashandisi yakanangana nemishonga mune yekutanga- uye yechipiri-mutsara kurapa, irinotecan inosanganisirwa nechinangwa chemishonga yekurapa inogona zvakare kutariswa.
Inotarisirwa kurapwa kwekenza yakajeka
Rondedzero yeakananga uye immunotherapy mishonga yekenza yakajeka yakagamuchirwa kusvika zvino kumba nekunze.
1. Bevacizumab
Zita rakajairika: An Wei Ting
Chirungu zita: Avastin
Molecular chimiro zita: Bevacizumab
Zviratidzo zvikuru: kenza yakajeka
Kubva: Roche
Bevacizumab (Avastin®) inogadzirisazve humanized monoclonal antibody. Yakagamuchirwa neDFA musi waFebruary 26, 2004, uye waive mushonga wekutanga wakabvumidzwa muUnited States kudzora bundu angiogenesis.
Kubudirira kwe bevacizumab seimwechete mumiriri yakaderera, uye inowanzo kukurudzirwa kuti ishandiswe mukubatana nekemotherapy.
Yakasanganiswa chemotherapy regimen: IFL, FOLFIRI, FOLFOX uye CapeOX; mishonga inoshandiswa: 5 mg / kg (2-vhiki regimen) uye 7.5 mg / kg (3-vhiki regimen).
Iko kusanganiswa kwe IFL uye bevacizumab mukurapa kenza yemhando yepamusoro yakawedzera OS kubva pamwedzi 15.6 kusvika pamwedzi 20.3 (AVF2107 kudzidza).
Bevacizumab combined with FOLFIRI regimen as first-line treatment, the effective rate was 58.7%, PFS was 10.3 months (FIRE3 study).
Bevacizumab inosanganiswa neFOLFOX kana FOLFIRI semutsara wekutanga kurapwa, PFS yakasvika gumi nemwedzi gumi nemana, OS yakasvika pamwedzi 11.3 (CALGB31.2 kudzidza).
2. Cetuximab
Zita rakajairika: Erbitux
Chirungu zita: CETUXIMAB SOLUTION YEMAHARA
Molecular chimiro zita: Cetuximab
Zviratidzo zvikuru: kenza yakajeka
Nzvimbo Yekutangira: Merkelion, Germany
Usati warapwa necetuximab, iro reRAS geni rinofanira kuongororwa pamberi pevose varwere vemusango vanogona kushandisa cetuximab. Chiyero chinoshanda checetuximab chinongova che20%, uye inowanzo kukurudzirwa kuti ishandiswe mukubatana nekemotherapy.
FOLFIRI uye FOLFOX; dosage: 400mg / m2 250mg / m2 pavhiki mushure mekutanga kwedosi.
MuRAS yemhando-yevarwere varwere, cetuximab inosanganisirwa neFOLFIRI regimen kana FOLFOX regimen inounza zvakanyanya kureba PFS uye OS pane chemotherapy chete.
3. Regafini
Zita rakajairika: Baivango
Chirungu zita: regorafenib
Molecular chimiro zita: Regefenib
Zviratidzo zvikuru: metastatic colorectal cancer
Nzvimbo Yekutangira: Bayer Corporation
Vanhu vanoshanda: MunaGunyana 2012, Regefini akabvumidzwa neDFA kurapa gomarara repamberi rekoloni. Muna Chivabvu 2017, CFDA yeChina yakabvumidza regorafenib yekurapa fluorouracil, oxaliplatin, uye irinotecan-based chemotherapy uye anti-VEGF therapy 1. Anti-EGFR therapy (RAS yemhando-yerudzi) varwere vane metastatic colorectal cancer (mCRC).
4. Panitumumab (panitumumab)
Zita rakajairika: Viktibi
Chirungu zita: Erbitux cetuximab
Molecular chimiro zita: panitumumab
Zviratidzo zvikuru: metastatic colorectal cancer
Nzvimbo Yekutangira: American 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-aflibercept (Abercept)
Chirungu zita: Zaltrap (ziv-aflibercept yekugadzirisa infusion)
Molecular chimiro zita: Abecip
Zviratidzo zvikuru: metastatic colorectal cancer
Kwakatangira: Sanofi
Abecip yakatenderwa neUSA FDA yekurapa kenza yemhando yepamusoro muna2012. Icho chimeric protein mushonga unodzivirira kupihwa kwehutachiona zvinovaka muviri nekudzivirira kwevanhu vascular endothelial kukura chinhu VEGF, nekudaro ichitadzisa kuwanda kwemarara.
Aflibercept inosunga kutenderera VEGF mumuviri uye inoita se "VEGF musungo". Naizvozvo, ivo vanodzivisa chiitiko chevascular endothelial kukura chinhu subtypes VEGF-A uye VEGF-B uye placental kukura chinhu (PGF), zvichiteerana, uye inodzivisa kukura kwemidzi mitsva yeropa mumakoriyori echironda kana mamota. Zvinogona kutaurwa kuti chinangwa cheAflibercept ndechekuti "ufe nenzara" bundu rechipfuva.
6. Ramolimumab (Cyramza)
Chirungu zita: ramucirumab
Molecular chimiro zita: Remolumumab
Zviratidzo zvikuru: kenza yakajeka
Kwayakatangira: Eli Lilly uye Kambani
Cyramza was approved by the US FDA in 2014 to treat gastric cancer, colorectal cancer and non-small cell lung kenza.
Sezvo bundu rechipfuva parinokura, inozoitika nzira yeangiogenesis, ndiko kuti, kuumbwa kwemidzi mitsva yeropa yakatenderedza bundu returu kutakura zvinovaka muviri kumaseru emota. Naizvozvo, kudzivisa iyi maitiro kunogona kudzivisa kuwanda kwemamota mazhinji.
Cyramza imonoclonal antibody drug, iyo inonyanya kudzvinyirira kuumbwa kwemidzi mitsva yeropa yakatenderedza bundu uye inodzivirira kugoverwa kwezvinovaka muviri kubundu nekusunga kune yevascular endothelial grow factor receptor (VEGFR2), zvichidaro ichitadzisa kukura kwechirwere.
7. Fruquintinib
Chigadzirwa Chigadzirwa: Aiyoute
Zviratidzo zvinoshanda: Yakagamuchirwa kuChina munaGunyana 5 pakurapwa kwekare fluorouracil, oxaliplatin uye irinotecan-based chemotherapy, pamwe neyekare kana isina kukodzera kurapwa neanti-vascular endothelial kukura chinhu (VEGF) 1. Varwere vane metastatic CRC inorapwa neanti- Epidermal kukura factor receptor (EGFR) (RAS yemusango-mhando).
7.opdivo
Chirungu zita: nivolumab
Molecular chimiro zita: nivolumab
Zviratidzo zvikuru: kenza yakajeka
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®.
Iyo yazvino kurapwa kufambira mberi kwekenza yakajeka kenza
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.
Iyo mPFS yeboka reTT-B rakarapwa neTAS102 + bevacizumab yaive mwedzi 9.2, iyo yaive yakakwira zvakanyanya kupfuura mwedzi 7.8 yechinyakare inorapwa capecitabine + bevacizumab CB boka. Kufambira mberi-kusununguka kupona. Inotarisirwa kuve nyowani yekutanga-tambo yekurapa sarudzo yevarwere vakadaro.
2) Ndeapi mabhenefiti ekurapa kwekurapa mune matatu-madhiragi musanganiswa?
Iko kusanganisa kwe encorafenib, 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.
Dzazvino dhata dzakatumirwa ku2018 World Congress yeGastrointestinal Cancer inoratidza kuti iwo matatu-madhiragi musanganiswa kwete chete ane yakakwira yekupindura mwero, asi zvakare ane refu PFS uye OS. Ichi ndicho chikonzero miedzo iri kuvandudzwa mune yekutanga-tambo kurapwa. Sezvineiwo, katatu iyi haina cytotoxic yakanangwa zvinodhaka. Izvi zvinoratidza kuti inogona nehungwaru kuona mamota mamorekuru uye nekugadzira akakosha emakiriniki mhedzisiro isina kuunza huturu hwakawanda.
3) Ndeapi mafambiro e immunotherapy?
Kune maMSI-H mamota, kusangana kwe nivolumab uye ipilimumab kune mukana wekuwana wekutanga kurapwa, nekuti data rekuita rinoratidzika kunge rinogutsa.
Kune microsatellite yakagadzikana mamota, tinofanirwa here kubatanidza immunotherapy neyakajairwa chemotherapy-FOLFOX / bevacizumab mukubatana nivolumab.
