Hana ʻo AASraw i nā pauka NMN a me NRC i ka nui!

ʻO Dacomitinib

 

  1. Ua ʻae ʻo FDA i ka dacomitinib no ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi metastatic
  2. He aha ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi?
  3. Ke noi noi Dacomitinib i ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi
  4. Nānā ʻo Dacomitinib
  5. ʻO Dacomitinib Mekanism o ka hana
  6. Hoʻohana ʻo Dacomitinib
  7. Nā hopena ʻaoʻao ʻo Dacomitinib
  8. ʻO ka mālama ʻana i ka maʻi ʻaʻa liʻiliʻi liʻiliʻi liʻiliʻi: Dacomitinib VS Gefitinib
  9. Pehea e kūʻai ai i ka Powle Dacomitinib ma ka pūnaewele?

 

FUa ʻae ʻo DA i ka dacomitinib no ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi metastatic

Ma ka lā 27 Kepakemapa 2018, ua ʻae ka Food and Drug Administration i nā papa dacomitinib (VIZIMPRO, ʻo Pfizer Pharmaceutical Company) no ka lālani mua o nā mea maʻi me ka metastatic maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi ʻole (NSCLC) me ka mea ulu epidermal factor receptor (EGFR) exon 19 holoi a i ʻole exon 21 L858R hoʻololi hoʻololi i ʻike ʻia e kahi hōʻike i ʻāpono ʻia e FDA.

Hoʻokumu ʻia ka ʻae ma ka randomized, multicenter, open-label, active control trial (ARCHER 1050; NCT01774721) e hoʻohālikelike ana i ka palekana a me ka pono o dacomitinib i gefitinib i nā maʻi 452 me ka NSCLC metastatic kūpono ʻole. Koi ʻia nā mea maʻi e loaʻa ʻole ka hoʻomaʻamaʻa mua no ka maʻi metastatic a i ʻole ka maʻi hoʻi hou me ka liʻiliʻi o 12 mau mahina ma hope o ka pau ʻana o ka ʻōnaehana non-EGFR TKI-i loaʻa ka lāʻau; kahi kūlana hana o ka ʻĀina Hui ʻĀina Hui Pū ʻIa o 0 a 1 paha; a me EGFR exon 19 holoi a exon 21 L858R hoʻololi hoʻololi. Hoʻohui ʻia nā mea maʻi (1: 1) e loaʻa iā dacomitinib 45 mg waha waha hoʻokahi i kēlā me kēia lā a i ʻole gefitinib 250 mg waha waha i kēlā me kēia lā a hiki i ka holomua ʻana o ka maʻi a i ʻole ka ʻawahia ʻae ʻole ʻia.

Ua hōʻike ka hoʻokolokolo i kahi hoʻomaikaʻi koʻikoʻi i ke ola kū ʻole holomua; ʻaʻole hōʻike ʻia kahi hoʻomaikaʻi o ka pane pane a i ʻole ke ola holoʻokoʻa. ʻO ke ola waena manuahi-ʻole ke ola ʻana, e like me ka mea i hoʻoholo ʻia e kahi kōmike loiloi kūʻokoʻa. ʻo 14.7 a me 9.2 mau mahina ma ka dacomitinib a me nā mea gefitinib, (ka lākiō o ka pōʻino 0.59; 95% CI: 0.47, 0.74; p <0.0001).

Aia i loko o ka ʻikepili kaukaʻi ka ʻōlelo aʻoaʻo a me nā akahele no ka maʻi lele interstitial (ILD), ka maʻi diarrhea, a me nā hopena maikaʻi ʻole dermatologic. No nā maʻi he 394 i loaʻa ka dacomitinib, ua kū nā hopena maikaʻi ʻole ma 27%. ʻO nā hopena maikaʻi ʻole i hopena i ka hoʻopau ʻana i ka dacomitinib ʻo ia ka maʻi diarrhea a me ILD. ʻO ka maʻamau maʻamau (> 20%) nā hopena maikaʻi ʻole o dacomitinib he diarrhea, ruash, paronychia, stomatitis, hoʻemi i ka makemake, ʻili maloʻo, hoʻemi i ke kaupaona, alopecia, tale, a me pruritus).

 

He aha ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi?

ʻO ka maʻi ʻaʻai pūpū ka maʻi maʻi maʻi maʻamau loa ma ka honua holoʻokoʻa, me ka ʻoi aku ma mua o ʻelua miliona mau hihia hou i ʻike ʻia ma ka honua holoʻokoʻa ma kahi o 2018 mau pākēneka o nā maʻi āpau āpau e ʻike ʻia ma ke ʻano he liʻiliʻi liʻiliʻi, a ma kahi o 85 pākēneka o kēia mau metastatic, a i ʻole holomua, i ka hōʻailona .

EGFR he protein e kōkua i nā hunaola e ulu a māhelehele. Ke hoʻololi ʻia ka ʻaoʻao EGFR hiki iā ia ke kumu i ka protein i ka overactive e hopena ana i nā hunaola maʻi ʻaʻai. Hiki i nā hoʻololi EGFR ma 10 a 35 pākēneka o nā NSCLC tumors a puni ka honua, a ʻo nā hoʻololi pinepine ʻana e hoʻopau ʻia i exon 19 a me exon 21 L858R mea pani, kahi i hui pū ʻia ma mua o 80 pākēneka o ka ʻike e hoʻoulu nei i nā hoʻololi EGFR. Pili ka maʻi i nā helu ola haʻahaʻa a ʻo ka holomua o ka maʻi ka mea paʻakikī.

ʻO AASraw ka mea hana ʻoihana o Dacomitinib.

E ʻoluʻolu e kaomi ma aneʻi no ka ʻike ʻōlelo. Hana iā mākou

 

Ke noi noi Dacomitinib i ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi

ʻO Dacomitinib kahi hanauna ʻelua EGFR tyrosine kinase mea kāohi (TKI) i hiki ʻole ke hoʻopaʻa a kāohi iā EGFR / Her1, Her2 a me Her4 subtypes me kahi mana e like me nā TKI ʻē aʻe. I ka hoʻāʻo ARCHER 1050, hoʻomaikaʻi ʻia ke ola me ka holomua ʻole e dacomitinib i hoʻohālikelike ʻia me gefitinib, e kākoʻo ana iā dacomitinib ma ke ʻano he koho mua loa no ka maʻi ʻaʻaʻa liʻiliʻi liʻiliʻi liʻiliʻi me ka hoʻololi EGFR maʻalahi. E pili ana i ka nui o nā hanana hopena maikaʻi ʻole, ʻaʻole i hoʻemi ʻia ka hopena o dacomitinib a hiki ke hoʻoliʻiliʻi pono i ka hanana a me ke koʻikoʻi o nā hanana kūpilikiʻi. Ke noʻonoʻo nei i ka ʻōnaehana e ulu nei o ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi o EGFR-mutant, hiki i ke poʻo i ka wā e hiki mai ana ke hoʻohālikelike ma waena o dacomitinib a me osimertinib i hiki ke hāʻawi i ka ʻike nui e hoʻoholo ai i ka papa hana mālama TKI maikaʻi loa.

 

ʻO Dacomitinib

 

ʻO ke kūlana kiʻekiʻe o ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi ua koi iā mākou e noʻonoʻo e pili ana i nā koho lapaʻau, pehea e ʻike ai i nā ʻano hana maikaʻi? ʻO Dacomitinib e paipai ʻia ka lapaʻau ʻana i kēlā me kēia. A laila, e nānā kāua ʻO Dacomitinib:

 

Nānā ʻo Dacomitinib

ʻO Dacomitinib, hoʻolālā ʻia e like me (2E) -N-16-4- (piperidin-1-yl) akā-2-enamide, kahi ʻāpana quinazalone i koho nui ʻia o ka waha o ka lua o ka hanauna tyrosine kinase inhibitors i ʻano e ka paʻa hiki ʻole ke hoʻololi ʻia ma. ka pae ATP o nā ʻāpana ulu ʻohana epidermal receptor kinase domains. ʻO Dacomitinib kahi lāʻau no ka mālama ʻana i ka maʻi liʻiliʻi liʻiliʻi liʻiliʻi liʻiliʻi (NSCLC). He mea koho a koho ʻole hiki ʻole ke hoʻihoʻi ʻia o EGFR.

Ua hoʻomohala ʻia ʻo Dacomitinib e Pfizer Inc a ʻae ʻia e ka FDA ma Kepakemapa 27, 2018. ʻO kekahi mau hōʻike i nā puke e hōʻike ana i ka hiki ke hoʻōla ʻia o dacomitinib i ka hoʻohālikelike maʻi ʻaʻai ovarian epithelial, ʻoiai e pono ai nā noiʻi hou aku.

I kēia manawa, Dacomitinib pauka (CAS:1110813-31-4) hiki ke hāʻawi ʻia e AASraw mai Kina.

 

ʻO Dacomitinib Mekanism o ka hana

ʻO Dacomitinib kahi mea hiki ʻole ke hoʻololi i ka mole mole liʻiliʻi o ka hana o ka ʻohana epidermal factor factor receptor (EGFR) ʻohana (EGFR / HER1, HER2, a me HER4) kinases tyrosine. Loaʻa iā ia i ka pāpā ʻana i hiki ʻole ke hoʻihoʻi ʻia ma o ka hoʻopili ʻana i ka covalent i nā koena cysteine ​​i nā kāʻei catalytic o nā mea loaʻa ʻo HER. Ua hōʻike ʻia ka pilina o dacomitinib i kahi IC50 o 6 nmol / L.

He kuleana ko ka ʻohana ErbB a i ʻole epidermal ulu aʻe (EGF) i ka ulu ulu ʻana, metastasis, a me ke kūpaʻa hoʻomaʻamaʻa ʻana ma o ka hoʻoulu ʻana i nā ala hoʻohuli i lalo e like me Ras-Raf-MAPK, PLCgamma-PKC-NFkB a me PI3K / AKT ma o ka tyrosine kinase-driven phosphorylation ma ka carboxy-terminus.1 Ma kahi o 40% o nā hihia e hōʻike ana i ka hoʻonui ʻana o ka EGFR a me 50% o nā hihia e hōʻike nei i ka hoʻololi EGFRvIII e hōʻike ana i ka holoi ʻana e hana i ka hoʻomau hoʻomau ʻana o ka tyrosine kinase domain o ka mea loaʻa.

 

Hoʻohana ʻo Dacomitinib

ʻAe ʻia ʻo Dacomitinib e mālama: Ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi (NSCLC) i metastasize (pālahalaha ʻia i nā ʻāpana ʻē aʻe o ke kino). Hoʻohana ʻia ia ma ke ʻano he lālani mua i nā maʻi i loaʻa i ko lākou poʻe tumors kekahi mau hoʻololi EGFR.

Ke aʻo ʻia nei hoʻi ʻo Dacomitinib i ka mālama ʻana i nā ʻano maʻi ʻē aʻe.

 

Nā hopena ʻaoʻao ʻo Dacomitinib

Nā mea nui e hoʻomanaʻo e pili ana i nā hopena ʻaoʻao o dacomitinib:

▪ ʻAʻole ʻike ka hapa nui o nā poʻe i nā hopena ʻaoʻao dacomitinib i helu ʻia ma aneʻi.

▪ Kuhi pinepine ʻia nā hopena ʻaoʻao Dacomitinib e pili ana i ka hoʻomaka ʻana, ka lōʻihi a me ke koʻikoʻi.

▪ E hoʻomaikaʻi hou nā hopena Dacomitinib ma hope o ka pau ʻana o ka therapy.

▪ Hiki ke mālama ʻia nā hopena ʻaoʻao Dacomitinib. Nui a hewahewa nā koho e hoʻoliʻiliʻi a pale i nā hopena ʻaoʻao o dacomitinib.

ʻO AASraw ka mea hana ʻoihana o Dacomitinib.

E ʻoluʻolu e kaomi ma aneʻi no ka ʻike ʻōlelo. Hana iā mākou

 

ʻO nā hopena ʻē aʻe i maʻa mau (e ʻike ʻia ma mua o 30%) no nā mea maʻi e lawe ana i ka dacomitinib:

▪ ʻ Skinhiki ʻili

▪ maʻi maʻi koʻohune a fungal paha (paronychia)

▪ ʻili maloʻo

▪ Ke albumin haʻahaʻa

▪ Kalipuna haʻahaʻa

▪ Nā pae glucose kiʻekiʻe

▪ Pohā

▪ Wela ka waha

▪ Hoʻoemi i ka makemake

▪ Anemia (hemoglobin haʻahaʻa)

▪ Helu hela keʻokeʻo haʻahaʻa

▪ Hoʻonui i nā ʻenema ate

 

ʻO kēia nā hopena ʻaoʻao liʻiliʻi e ʻike ʻia (e loaʻa ana ma 10-29%) no nā mea maʻi e loaʻa ana i ka dacomitinib:

▪ ʻeha ʻeha

▪ ʻommoe ʻole

▪ Lilo ka lauoho

▪ Kāwili

▪ ʻO ka ʻulaʻula, ka pehu ʻana, a me ka ʻeha ma nā poho o nā lima a me / a i ʻole nā ​​kapuaʻi o nā wāwae

▪ Nā pae haʻahaʻa potassium, magnesium a me sodium

▪ Ka hoʻēmi kino

▪ Nausea

▪ Kaohi paʻa

▪ ʻeha ʻeha

▪ ʻeha puʻupuʻu puʻupuʻu

▪ Nāwaliwali / nele o ka ikehu

▪ Ka hoʻohauna a i ʻole ka maʻi o nā maka

▪ Hoʻonui i ka creatinine serum

▪ Cough, hōʻailona ihu a me nā ʻōuli, pilikia i ka hanu ʻana a me ka maʻi hanu luna o ka hanu

ʻAʻole i helu ʻia nā hopena ʻaoʻao āpau ma luna. ʻAno ʻole nā ​​hopena ʻaoʻao - e loaʻa ana ma lalo o 10 pakeneka o nā maʻi - ʻaʻole i helu ʻia ma aneʻi. Akā pono ʻoe e hoʻomaopopo mau i kāu mea mālama ola inā ʻike ʻoe i nā ʻōuli maʻamau.

 

ʻO ka mālama ʻana i ka maʻi ʻaʻa liʻiliʻi liʻiliʻi liʻiliʻi: Dacomitinib VS Gefitinib

Ma waena o nā mea maʻi me ka EGFR-maikaʻi, non-lolo metastatic non-liʻiliʻi pūnana maʻi ʻaʻai (NSCLC), ka laina mua dacomitinib hoʻomaikaʻi i ka holomua-manuahi ke ola (PFS) ma luna o gefitinib, e like me ka pae 3 hoʻopaʻa ʻia i paʻi ʻia ma ka Lancet Oncology.ʻO Dacomitinib

Hoʻohana ʻia nā hanauna mua EGFR – tyrosine kinase (TKI), me gefitinib, i ka lālani mua no nā mea maʻi me ka maʻi maʻi EGFR, i hoʻokumu ʻia ma waena o 10% a me 44% o nā adenocarcinomas āpau āpau. ʻAʻole i hoʻoholo ka hoʻopaʻa mua inā he ʻoi aku ka hanauna ʻelua ʻo EGFR-TKI ma mua o ka hanauna mua.

No kēia lepili hāmama, ke aʻo kaulike ʻia (ARCHER 1050; ClinicalTrials.gov Identifier: NCT01774721), a nā mea kākau i ʻōlelo ai ʻo ia ka papa hana 3 mua e hoʻohālikelike i ka hanauna EGFR-TKI ʻelua me kahi hanauna mua EGFR-TKI i kēia hoʻonohonoho , ua kākau inoa nā kānaka noiʻi 452 mau mea maʻi e loaʻa iā dacomitinib (227 mau maʻi) a i ʻole gefitinib (225 mau maʻi). ʻAʻole kūpono nā maʻi me nā metastases lolo.

Ma ka median ukali o 22.1 mahina, median PFS he 14.7 mahina no dacomitinib vs 9.2 mahina no gefitinib; ua makemake pū ʻia nā loiloi subgroup iā dacomitinib. He ʻumikūmālua mau pane piha i hoʻopaʻa ʻia i ka hui dacomitinib vs 4 i ka hui gefitinib. Akā, ua like nā helu pane pahuhopu (75% no dacomitinib a me 72% no gefitinib; P = .4234).

Iwakāluakūmākahi mau maʻi i loaʻa i ka dacomitinib i loaʻa kahi hanana kūʻē e pili ana i ka mālama ʻana (AE); he ʻoiaʻiʻo kēia no 10 mau maʻi e loaʻa ana iā gefitinib. Ua hōʻike ʻia nā make e pili ana i ka mālama ʻana no 2 mau maʻi e loaʻa ana iā dacomitinib vs 1 no gefitinib.

Ua pau nā mea kākau i ka ʻōlelo ʻo "dacomitinib lapaʻau ʻoi aku ma mua o ʻO Gefitinib e pili ana i ka [PFS] a me ka lōʻihi o ka pane ʻana i ka lālani mua o nā mea maʻi me ka EGFR-mutation-positive NSCLC a pono e noʻonoʻo ʻia ma ke ʻano he koho lapaʻau hou no kēia heluna kanaka. ”

 

Pehea e kūʻai ai i ka Powle Dacomitinib ma ka pūnaewele?

Nui a hewahewa nā mea hoʻolako / mea hana o ka pauka dacomitinib i ka mākeke, ke ʻike nei he mea nui ka mea nui no nā poʻe āpau e pono koke i kēia huahana. Ke hoʻoholo mākou e kūʻai i ka pauka dacomitinib i ka mākeke, pono mākou e aʻo hou e pili ana i ia mea, ʻike pehea e hoʻohana ai a ʻo ia ke ʻano o ka hana, nā pilikia ke lawe mākou i ka pauka dacomitinib…. Eia hou, ʻo ke kumukūʻai a me ka maikaʻi e lilo i kā mākou hopohopo ma mua o ka kūʻai ʻana.

Ma hope o kā mākou nānā ʻana i nā ʻikepili mai ka mākeke, hoʻohālikelike ʻia i nā mea hoʻolako, nānā maikaʻi ʻo AASraw no nā poʻe e makemake e kūʻai i ka nui. pauka dacomitinib, kāohi ʻia kā lākou hana ma lalo o ke kūlana cGMP, hiki ke nānā i ka maikaʻi i kēlā me kēia manawa a hāʻawi paha lākou i nā hōʻike hoʻāʻo a pau ke kauoha ʻoe. No nā kumukūʻai dacomitinib pauka / kumukūʻai, pono ia, i koʻu mau maka. Ma muli o ka loaʻa ʻana o nā kumukūʻai he nui mai nā mea hoʻolako like ʻole, hoʻohālikelike ʻia me ka maikaʻi, manaʻo wau ʻaʻole maikaʻi ʻole ka aasraw.

 

Reference

[1] Kobayashi Y, Fujino T, Nishino M, et al. EGFR T790M a me C797S hoʻololi e like me nā ʻano hana o ka loaʻa kūʻē ʻana i dacomitinib. J Thorac Oncol. 2018; 13 (5): 727-731. hana: 10.1016 / j.jtho.2018.01.009.

[2] Kris MG, Camidge DR, Giaccone G, et al. Ke kuhi nei i nā HER2 aberrations ma ke ʻano he mea hoʻokele hiki ke hana ʻia i nā maʻi ʻaʻaʻa: ʻo ka ʻāpana II ka hoʻāʻo o ka pan-HER tyrosine kinase inhibitor dacomitinib i nā mea maʻi me HER2-mutant a i hoʻonui ʻia paha nā tumors. ʻO Ann Oncol. 2015; 26 (7): 1421-1427. hana: 10.1093 / annonc / mdv383.

[3] Park K, Tan EH, O'Byrne K, et al. ʻO Afatinib me gefitinib ma ke ʻano he lālani mua o nā mea maʻi me ka EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): kahi pae 2B, hāmama lepili, hoʻowalewale hoʻokolohua hoʻokolohua ʻia. Lancet Oncol. 2016; 17 (5): 577-589. hana: 10.1016 / S1470-2045 (16) 30033-X.

[4] Lacouture ME, Keefe DM, Sonis S, et al. Ke aʻo II pae (ARCHER 1042) e loiloi i ka hoʻoponopono prophylactic o dacomitinib-induced dermatologic a me nā hanana kūpiliki gastrointestinal i ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi. ʻO Ann Oncol. 2016; 27 (9): 1712-1718. hana: 10.1093 / annonc / mdw227.

[5] ʻO Reckamp KL, Giaccone G, Camidge DR, et al. ʻO kahi hoʻokolohua ʻelua o dacomitinib (PF-2), kahi pan oral-irreversible pan ‐ HER (receptor mea ulu ulu epidermal kanaka), i nā mea maʻi me ka maʻi ʻaʻaʻi liʻiliʻi liʻiliʻi liʻiliʻi ma hope o ka holo pono ʻole ʻana o ka chemotherapy a me ka erlotinib mua. Kanesa. 00299804; 2014 (120): 8-1145. hana: 1154 / cncr.10.1002.

[6] Engelman JA, Zejnullahu K, Mitsudomi T, et al. Alakaʻi i ka hoʻonui MET i ke kūʻē ʻana gefitinib i ka maʻi ʻaʻai māmā e ka hoʻoulu ʻana i ka hōʻailona ERBB3. ʻEpekema. 2007; 316 (5827): 1039-1043. hana: 10.1126 / ʻepekema.1141478.

[7] Liu X, Wang P, Zhang C, et al. Epepermal factor factor receptor (EGFR): He hōkū piʻi i ke au o ka lāʻau lapaʻau pololei o ka maʻi ʻaʻai māmā. Oncotarget. 2017; 8 (30): 50209-50220.

[8] ʻO Girard N. Hoʻopōlomua i nā hopena i ka EGFR hoʻololi-maikaʻi NSCLC: ʻo ka mea nāna e kāohi i ka tyrosine kinase ahea ana? ʻO Future Oncol 2018.

[9] Inoue A, Kobayashi K, Maemondo M, et al. ʻO nā hopena hope loa o NEJ002, kahi hoʻāʻo pae III e hoʻohālikelike ana i ka gefitinib i ka carboplatin (CBDCA) a me paclitaxel (TXL) ma ke ʻano he lālani mua no ka maʻi ʻaʻa liʻiliʻi liʻiliʻi liʻiliʻi liʻiliʻi (NSCLC) me nā hoʻololi EGFR. ʻO J Clin Oncol 2011; 29: 7519.

[10] Sequist LV, Yang JC, Yamamoto N, et al. Ke aʻo ʻāpana III o afatinib a i ʻole cisplatin a me pemetrexed i nā mea maʻi me ka metastatic lung adenocarcinoma me nā hoʻololi EGFR. ʻO J Clin Oncol 2013; 31: 3327-34.

[11] Lin JJ, Cardarella S, Lydon CA, et al. ʻElima mau makahiki i ola i EGFR-Mutant Metastatic Lung Adenocarcinoma i mālama ʻia me EGFR-TKI. ʻO J Thorac Oncol 2016; 11: 556-65.

0 Likes
94 Views

E hiki no hoi i like

Comments ua paa.