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Afatinib

 

  1. He aha ʻo Afatinib?
  2. Ke makemake mākou iā Afatinib?
  3. Pehea e hana ai ʻo Afatinib?
  4. Ua ʻae ʻia ʻo Afatinib e FDA? ʻOiaʻiʻo
  5. He aha nā hopena a me nā ʻaoʻao ʻē aʻe i lawe ʻia e Afatinib?
  6. He aha nā noiʻi ʻē aʻe e pili ana iā Afatinib?

 

Heaha Is Afatinib?

Afatinib (CAS: 439081-18-2) he lāʻau hoʻomohala hoʻomālama ʻia i ʻike ʻia ʻo Giotrif. Hoʻohana ʻia ia e mālama i ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi (NSCLC) i hoʻomaka e hoʻolaha ma waho o ka akemā a i ʻole nā ​​ʻāpana ʻē aʻe o ke kino. Hiki nō ke hoʻohana e mālama i nā maʻi ʻino ʻē aʻe ma ke ʻano he hoʻokolohua hoʻokolohua.

ʻOi aku ka maikaʻi e heluhelu i kēia ʻike me kā mākou ʻike ākea e pili ana i ka maʻi ʻaʻai maʻi a i ʻole ke ʻano o ka maʻi ʻaʻai āu. E kamaʻilio pū kāu kauka iā ʻoe e pili ana i kēia lapaʻau a me nā hopena pili ʻē aʻe ma mua o kou ʻae ʻana (ʻae) e loaʻa ka lāʻau. I ka wā o ka mālama ʻana, ʻike ʻoe i ke kauka maʻi ʻaʻai a kahu maʻi paha. ʻO mākou kēia no mākou e ʻōlelo nei ke kauka a kahu hānai paha i kēia ʻike.

 

Ke makemake mākou Afatinib

Hiki ke hoʻohana ʻia ʻo Afatinib e mālama i ka maʻi ʻaʻai liʻiliʻi liʻiliʻi liʻiliʻi (NSCLC) i loaʻa:

♦ Hoʻolahalaha i nāʻaʻa puni (holomua kūloko)

♦ Hoʻolahalaha i nā ʻāpana ʻē aʻe o ke kino (holomua a metastatic paha).

Hana wale ʻo Afatinib no nā maʻi ʻaʻai i loaʻa kahi ʻano ʻokoʻa o kahi protein i kapa ʻia ʻo epeptoral factor factor receptor (EGFR). Hana ʻia nā hoʻokolohua ma nā hunaola maʻi ʻaʻai mai kahi biopsy a i ʻole ke ʻoki mua e nānā i ka pae o EGFR. ʻLelo kēia i kāu kauka inā e hana paha ʻo afatinib iā ʻoe.

 

Pehea Afatinib Hana?

He ikaika a koho ʻo Afatinib, blocker ʻohana ErbB hiki ʻole ke hoʻoliʻiliʻi. Hoʻopili ʻo Afatinib i nā poloka a me ka hiki ʻole ke hoʻololi i nā hōʻailona mai nā homo a me nā heterodimers āpau i hoʻokumu ʻia e nā ʻohana ErbB EGFR (ErbB1), HER2 (ErbB2), ErbB3 a me ErbB4.

Ma kahi kikoʻī, hoʻopaʻa paʻa ʻo afatinib i nā kāʻei kinase o EGFR (ErbB1), HER2 (ErbB2), a me HER4 (ErbB4) a me ka pāpā ʻole i ka tyrosine kinase autophosporylation, a laila ka hopena o ka hōʻailona ErbB. ʻO kekahi mau hoʻololi i ka EGFR, me nā hoʻololi kū ʻole i loko o kāna kāʻei kinase, hiki i ka hopena ke hoʻonui i ka autophosphorylation o ka mea loaʻa, e alakaʻi ana i ka hoʻoulu ʻana o nā receptor, i kekahi manawa me ka ʻole o ka paʻa ʻana o ka ligand, a hiki ke kākoʻo i ka hoʻonui ʻana o ka cell i NSCLC. Hoʻohālikelike ʻia nā hoʻololi hoʻololi ʻole e like me nā hanana i exons e hoʻokumu ana i ka domain kinase o EGFR e alakaʻi ai i ka hoʻonui ʻana o ka receptor activation a ma kahi e wānana ʻia ai ka efficacy e 1). a i ʻole EGFR tyrosine kinase phosphorylation ma nā concentrations o afatinib mea hoʻomau i nā mea i koi ʻia e like me nā hana i hōʻoia ʻia. ʻO nā mea i ʻike pinepine ʻia o kēia mau hoʻololi ʻana he exon 2 L21R substitutions a me exon 858 Delete.

Eia kekahi, ua hōʻike ʻo afatinib i ka pāpā ʻana o autophosphorylation a me / a i ʻole ka vitro hoʻolaha ʻana o nā laina pūnaewele e hōʻike ana i nā ʻano hihiu o EGFR a i kēlā mau mea e hōʻike nei i nā koho EGFR exon 19 e holoi i nā hoʻololi, exon 21 L858R mutations, a i ʻole nā ​​hoʻololi hoʻololi kū ʻole ʻole liʻiliʻi, i nā afatinib concentrations i loaʻa. i nā mea maʻi. Eia hou, ua kāohi ʻo afatinib i ka hoʻolaha vitro o nā laina pūnaewele e hōʻike ana iā HER2.

ʻO AASraw ka mea hana ʻoihana o Afatinib.

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

 

He aha Afatinib Ua ʻae ʻia e FDA? ʻOiaʻiʻo

Hāʻawi ka ʻae i kahi koho lapaʻau lālani hou hou no nā mea maʻi me ka lua o ka sub-type o ka liʻiliʻi liʻiliʻi ʻole lung maʻi 'aʻai (NSCLC), e hōʻike ana ma kahi o 20-30% o nā hihia NSCLC

Hoʻokumu ʻia ka ʻae ma nā hopena o ka noi ʻo LUX-Lung 8, kahi i hōʻike maikaʻi loa i ke ola āpau a me ke ola me ka holomua ʻole e hoʻohālikelike ʻia iā Tarceva (erlotinib) i nā mea maʻi me ka carcinoma squamous cell of the lung

Afatinib ua ʻae ʻia ma nā ʻāina he 60 a ʻoi aku no ka mālama ʻana i nā mea maʻi me nā ʻano like ʻole o ka EGFR mutation-positive NSCLC

Afatinib

He aha ka pilikia/ Nā hopena ʻaoʻao hana Afatinib Lawe mai? 

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

▪ ʻAʻole ʻike ka hapanui o nā poʻe i nā hopena ʻaoʻao afatinib i helu ʻia.

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

▪ ʻAneʻane hiki ke hoʻohuli i nā hopena ʻaoʻao Afatinib a hele aku ma hope o ka pau ʻana o ka lāʻau.

▪ Hiki ke mālama ʻia nā hopena ʻĀina ʻo Afatinib. Nui a hewahewa nā koho e hoʻoliʻiliʻi a pale i nā hopena ʻaoʻao o afatinib.

 

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

▪ Pohā

▪ Hū ka huehue (ka hui o nā ʻili i like me ka huehue)

▪ Wela ka waha

▪ Paronychia (maʻi o nā kui)

▪ waha maloo

 

ʻO kēia nā hopena ʻē aʻe i ʻike pinepine ʻia (e loaʻa ana ma 10-29%) no nā mea maʻi e loaʻa ana iā afatinib:

▪ Hoʻoemi i ka makemake

▪ Kāwili

▪ Ka hoʻēmi kino

▪ Kahe ka ihu

▪ Cystitis (maʻi ʻaʻai)

▪ Cheilitis (pehu o nā lehelehe)

▪ Fiva

▪ Hypokalemia (potassium haʻahaʻa)

▪ Conjunctivitis (maka poni)

▪ Rhinorrhea (ihu ihu)

▪ Nā ʻenekia ate kiʻekiʻe

ʻAʻole i helu ʻia nā hopena ʻaoʻao āpau ma luna. Kekahi mau mea kākaʻikahi (e hana ʻia ma lalo o 10 pākēneka o nā maʻi) ʻaʻole i helu ʻia ma aneʻi. Hoʻomaopopo mau i kāu mea mālama ola inā ʻike ʻoe i nā ʻōuli maʻamau.

 

He aha nā noiʻi ʻē aʻe Afatinib?

 ʻO Afatinib (BIBW 2992) ulu i ka maʻi ʻaʻai liʻiliʻi liʻiliʻi ʻole

ʻO Afatinib (BIBW 2992), kahi puke aniline – quinazoline derivative, i hiki ʻole ke hoʻololi ʻia a mākaukau pono ʻia i ka hana kinase intrinsic o nā ʻohana ʻohana receptor ErbB hana. Hōʻike nā hopena Preclinical he maikaʻi ka afatinib i nā ʻōnaehana maʻi ʻaʻai pūhū, e like me nā mea me nā loiloi ʻo EGF (EGFR) kūpaʻa i nā mea hoʻohuli EGFR hanauna mua hiki ke hoʻohuli ʻia. Ke nānā ʻia nei ʻo Afatinib ma ka papahana LUX-Lung, kahi e loiloi ai iā afatinib ma ke ʻano he lapaʻau mua i nā mea maʻi me nā hoʻololi EGFR-activating (LUX-Lung 2, 3 a me 6) a ma ke ʻano he laina ʻelua a ʻekolu paha i nā maʻi. i loaʻa ke kūʻē iā gefitinib a me / a i ʻole erlotinib (LUX-Lung 1, 4 a me 5). Ua hōʻike ʻo LUX-Lung 1 a me 2, ma waena o kā lākou mau pūʻulu pahuhopu, kahi piʻi nui o ka nui o ka mālama ʻana i nā maʻi o 58 a me 86%, a me ka hoʻolōʻihi ʻana i ke ola me ka manuahi o ka holomua. Ke hoʻomau nei nā hoʻokolohua hoʻokolohua Phase III hou e loiloi i ka afatinib me ka paclitaxel (LUX-Lung 5), a hoʻohālikelike ʻia me cisplatin / pemetrexed (LUX-Lung 3) a i ʻole cisplatin / gemcitabine (LUX-Lung 6).

ʻO AASraw ka mea hana ʻoihana o Afatinib.

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

 

 ʻO Afatinib i ka chordoma holomua a me ka metastatic chordoma

ʻO kēia kahi hoʻāʻo Phase 2 e hoʻopaʻa nei i ka pono o a lāʻau lapaʻau maʻi ʻaʻai i kapa ʻia ʻo afatinib. Hoʻopili ʻo Afatinib i ka protein EGFR, ka mea i manaʻo ʻia e pili ana i ka hoʻoulu ʻana i ka ulu o nā tumo chordoma. Hoʻonohonoho pono ʻia kēia noi no nā mea maʻi chordoma 18 makahiki a ʻoi paha me nā tumors recurrent a metastatic paha. E wehe ʻia ia ma Leiden University Medical Center (LUMC) a me ka University Hospital London Hospital (UCLH) a e wehe ʻia ma Istituto dei Nazionale Tumori (INT) ma Milan i nā mahina e hiki mai ana. ʻO nā mea noiʻi nui no kēia noi ʻo Kauka Hans Gelderblom ma LUMC, Kauka Silvia Stacchiotti ma INT, a me Kauka Sandra Strauss ma UCLH.

ʻO ka Epidermal Growth Factor Receptor (EGFR) kahi protein i loaʻa ma ka papa o kekahi mau huna i loko o ke kino. ʻO ka maʻamau, kōkua ʻo EGFR i ka hoʻoponopono ʻana i ka ulu ʻana o ka pūnaewele a hana i kahi hana i ka hōʻeha ʻana i ka ʻeha. I kekahi mau maʻi ʻino, me ka hapa nui o nā chordomas, lilo ʻo EGFR i overactive, alakaʻi i nā hunaola maʻi ʻaʻai e hoʻonui i waho o ka kaohi.

ʻO nā lāʻau e ālai iā EGFR i kapa ʻia ʻo "EGFR inhibitors" ʻae ʻia e mālama i nā ʻano ʻano like ʻole o ka maʻi ʻaʻai. ʻO Afatinib kahi mea kāohi EGFR i ʻae ʻia i kēia manawa e mālama i ka maʻi ʻaʻai liʻiliʻi liʻiliʻi ʻole a ke hoʻāʻo ʻia nei i nā ʻano tumo ʻē aʻe.

Ua hōʻike ʻia kekahi mau mea hoʻopale EGFR e lohi a kū i ka ulu ʻana o nā pūnaewele chordoma a me nā tumors chordoma i nāʻiole. ʻO nā mea āpau EGFR āpau i hoʻāʻo ʻia, ʻo afatinib ka mea i ʻoi loa i nā mana o kaʻiole o chordoma. I kekahi mau hiʻohiʻona iole, hoʻolohi ia i ka ulu ʻana o nā tumors, ʻoiai ma nā mea ʻē aʻe e hōʻemi nui i nā tumors. Hoʻoholo kēia hoʻokolohua e hoʻoholo inā hiki i ka afatinib ke hōʻemi a hoʻopau paha i ka ulu ʻana o nā tumo chordoma i nā mea maʻi me ka maʻi hou a metastatic paha.

 

Reference

[1] Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel Frühjahr 2013. (i ka Kelemania)

[2] Spreitzer H (13 Mei 2008). "Neue Wirkstoffe - Tovok". Österreichische Apothekerzeitung (i Kelemania) (10/2008): 498.

[3] Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, et al. (ʻAukake 2008). "BIBW2992, kahi mea hoʻohuli EGFR / HER2 i hiki ʻole ke hoʻoliʻiliʻi maikaʻi loa i nā mana maʻi ʻaʻai maʻi preclinical". ʻO Oncogene. 27 (34): 4702-11. hana: 10.1038 / onc.2008.109. PMC 2748240. PMID 18408761.

[4] "Giotrif: EPAR -Product Information" (PDF). ʻOihana Lapaʻau ʻEulopa. ʻO Boehringer Ingelheim International GmbH. 16 ʻOkakopa 2013. Ua kiʻi ʻia 28 Ianuali 2014.

[5] Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, et al. (Kekemapa 2015). "EGFR Exon 18 Hoʻololi i ka maʻi ʻaʻai puʻu: Molecular Predictors o Augmentedib Sensitivity i Afatinib a i ʻole Neratinib ke hoʻohālikelike ʻia me nā TKI hanauna mua a i ʻole ʻekolu". ʻImi ʻ Cancerlelo Kānā Haukino. 21 (23): 5305–13. hana: 10.1158 / 1078-0432.CCR-15-1046. PMID 26206867.

[6] Lin NU, Winer EP, Wheatley D, Carey LA, Houston S, Mendelson D, et al. (Iune 2012). "Ke aʻo II mahele o afatinib (BIBW 2992), kahi blocker ʻohana ErbB hiki ʻole ke hoʻi, i nā mea maʻi me ka HER2-positive metastatic cancer cancer e holo nei ma hope o trastuzumab". ʻImi a me ka mālama ʻana i ka maʻi ʻaʻai umauma. 133 (3): 1057-65. hana: 10.1007 / s10549-012-2003-y. PMC 3387495. PMID 22418700.

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