amakuru

Cachexia ni indwara itunganijwe irangwa no kugabanya ibiro, imitsi na adipose tissue atrophy, hamwe no gutwika sisitemu. Cachexia nimwe mubibazo nyamukuru bitera impfu kubarwayi ba kanseri. Bigereranijwe ko indwara ya cachexia ku barwayi ba kanseri ishobora kugera kuri 25% kugeza kuri 70%, kandi abantu bagera kuri miliyoni 9 ku isi barwara cachexia buri mwaka, 80% muri bo bikaba biteganijwe ko bapfa mu gihe cy'umwaka umwe basuzumwe. Byongeye kandi, cachexia igira ingaruka cyane mubuzima bwumurwayi (QOL) kandi ikongerera uburozi bujyanye no kuvura.

Gutabara neza kwa cachexia bifite akamaro kanini mukuzamura imibereho no kumenyekanisha abarwayi ba kanseri. Nubwo, nubwo hari intambwe imaze guterwa mu kwiga uburyo bwa pathophysiologique ya cachexia, imiti myinshi yakozwe ishingiye ku buryo bushoboka irakora neza cyangwa ntigire icyo ikora. Kugeza ubu nta muti ufatika wemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA).

Cachexia (syndrome de syndrome) ikunze kugaragara cyane ku barwayi bafite kanseri zitandukanye, akenshi bikaviramo kugabanuka ibiro, guta imitsi, kugabanuka k'ubuzima, imikorere mibi, no kubaho igihe gito. Ukurikije amahame yemeranijwe ku rwego mpuzamahanga, iyi syndrome ya multifactorial isobanurwa nkurutonde rwumubiri (BMI, uburemere [kg] ugabanijwe nuburebure [m] kwaduka) munsi ya 20 cyangwa, kubarwayi barwaye sarcopenie, gutakaza ibiro birenga 5% mumezi atandatu, cyangwa gutakaza ibiro birenga 2%. Kugeza ubu, nta biyobyabwenge byemewe muri Amerika no mu Burayi by’umwihariko byo kuvura kanseri ya kanseri, bikavamo uburyo buke bwo kuvura.
Amabwiriza ya vuba aha yerekana olanzapine nkeya kugirango yongere ubushake nuburemere kubarwayi barwaye kanseri yateye imbere ahanini bishingiye kubyavuye mu bushakashatsi bwakozwe n'ikigo kimwe. Usibye ibi, gukoresha igihe gito kugereranya progesterone cyangwa glucocorticoide birashobora gutanga inyungu nke, ariko harikibazo cyingaruka mbi (nko gukoresha progesterone ijyanye nibintu bya tromboembolique). Igeragezwa rya Clinical yandi miti yananiwe kwerekana imikorere ihagije kugirango yemerwe namabwiriza. Nubwo anamorine (verisiyo yo mu kanwa ya hormone yo gukura irekura peptide) yemerewe mu Buyapani kuvura kanseri ya kanseri, imiti yongereye umubiri gusa ku rugero runaka, ntabwo yongereye imbaraga zo gufata, kandi amaherezo ntiyemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA). Hano harakenewe byihutirwa kuvurwa neza, neza kandi bigamije kuvura kanseri ya kanseri.
Gukura gutandukanya ibintu 15 (GDF-15) ni cytokine iterwa no guhangayika ihuza na glia ikomoka kuri glia ikomoka kuri neurotrophique yibintu byakira reseptor alpha-nka proteine ​​(GFRAL) mubwonko bwinyuma. Inzira ya GDF-15-GFRAL yamenyekanye nkigenzura rikomeye rya anorexia no kugabanya ibiro, kandi igira uruhare mu gutera indwara ya cachexia. Mubyitegererezo byinyamanswa, GDF-15 irashobora gutera cachexia, kandi kubuza GDF-15 birashobora kugabanya iki kimenyetso. Byongeye kandi, urwego rwinshi rwa GDF-15 ku barwayi ba kanseri rufitanye isano no kugabanya ibiro by’umubiri hamwe n’imitsi ya skeletale, kugabanuka kwimbaraga, no kubaho igihe gito, bishimangira agaciro ka GDF-15 nkintego yo kuvura.
ponsegromab (PF-06946860) ni antibody ihitamo abantu cyane ya monoclonal antibody ishobora guhuza ikwirakwizwa rya GDF-15, bityo ikabuza imikoranire yayo na reseptor ya GFRAL. Mu igeragezwa ritoya rya label icyiciro cya 1b, abarwayi 10 barwaye kanseri ya cachexia hamwe no kuzamura urwego rwa GDF-15 bavuwe hamwe na ponsegromab kandi bagaragaza ko bateye imbere mubiro, ubushake bwo kurya, nibikorwa byumubiri, mugihe serumu GDF-15 yabujijwe kandi ibintu bibi byari bike. Dufatiye kuri ibi, twakoze ikizamini cyo mu cyiciro cya 2 cyo gusuzuma kugira ngo dusuzume umutekano n’akamaro ka ponsegromab ku barwayi barwaye kanseri ya kanseri ifite umuvuduko ukabije wa GDF-15, ugereranije na placebo, kugira ngo dusuzume hypothesis ivuga ko GDF-15 ari yo ntandaro y’indwara.
Ubushakashatsi bwarimo abarwayi bakuze barwaye cachexia ifitanye isano na kanseri (kanseri y'ibihaha itari mito mito, kanseri yandura, cyangwa kanseri yibara) hamwe na serumu GDF-15 byibuze 1500 pg / ml, amanota yubuzima bwa Eastern Tumor Consortium (ECOG) amanota ≤3, kandi ikizere cyo kubaho byibuze amezi 4.
Abarwayi biyandikishije bahawe amahirwe yo kwakira dosiye 3 za ponsegromab 100 mg, 200 mg, cyangwa 400 mg, cyangwa placebo, munsi y'ubutaka buri byumweru 4 ku kigereranyo cya 1: 1: 1. Iherezo ryibanze ryari impinduka muburemere bwumubiri ugereranije na baseline mubyumweru 12. Icyiciro cya kabiri cyanyuma cyari impinduka kuva kumurongo wibanze muri anorexia cachexia Sub-Scale (FAACT-ACS) amanota, isuzuma ryimikorere yo kuvura cachexia ya anorexia. Izindi ndunduro ya kabiri yarimo kanseri ifitanye isano na kanseri yerekana ibimenyetso bya buri munsi, impinduka zifatizo mubikorwa byumubiri hamwe nu rugendo rwapimwe hifashishijwe ibikoresho byubuzima byambarwa. Igihe ntarengwa cyo kwambara gisabwa mbere. Isuzuma ry’umutekano ryarimo umubare wibyabaye bibi mugihe cyo kuvura, ibisubizo bya laboratoire, ibimenyetso byingenzi, na electrocardiogram. Iherezo ryubushakashatsi ryarimo impinduka zifatizo mubice byerekana imitsi ya skeletale (agace k'imitsi ya skeletale igabanijwe n'uburebure bwa kare) ifitanye isano n'imitsi ya skeletale.

Abarwayi 187 bose bahawe inshingano zo kwakira ponsegromab 100 mg (abarwayi 46), mg 200 (abarwayi 46), 400 mg (abarwayi 50), cyangwa umwanya wa (abarwayi 45). Mirongo irindwi na bane (40 ku ijana) barwaye kanseri y'ibihaha itari ntoya, 59 (32 ku ijana) barwaye kanseri y'urwagashya, naho 54 (29 ku ijana) barwaye kanseri y'urura runini.
Itandukaniro riri hagati ya mg 100, mg 200, na 400 mg hamwe na placebo byari kg 1,22, kg 1.92, na 2.81 kg.

Igishushanyo cyerekana iherezo ryibanze (guhindura uburemere bwumubiri kuva kuri baseline kugeza ibyumweru 12) kubarwayi barwaye kanseri cachexia mumatsinda ya ponsegromab na placebo. Nyuma yo guhindura ibyago byo gupfa byurupfu nibindi bintu byahuriranye, nko guhagarika imiti, iherezo ryambere ryasesenguwe nicyitegererezo cya Emax cyifashishijwe ibisubizo byicyumweru 12 bivuye mubisesengura ryigihe kirekire cya Bayesian (ibumoso). Iherezo ryibanze naryo ryasesenguwe muburyo busa, hifashishijwe intego zagereranijwe zo kuvurwa nyirizina, aho kwitegereza nyuma yibyabaye byose byagabanijwe (ishusho iburyo). Intera y'icyizere (yerekanwe mu ngingo

Ingaruka za mg 400 ponsegromab ku buremere bw'umubiri zahoraga mu matsinda mato mato mato, harimo ubwoko bwa kanseri, serumu GDF-15 yo mu rwego rwa quartile, imiti ya chimiotherapie ishingiye kuri platine, BMI, hamwe na sisitemu yo gutwika. Guhindura ibiro byari bihuye na GDF-15 kubuza ibyumweru 12.

Guhitamo amatsinda mato yari ashingiye ku isesengura ryakozwe na Bayesian nyuma y’igihe kirekire, ryakozwe nyuma yo guhindura ingaruka z’urupfu rushingiye ku ntego ziteganijwe mu ngamba zo kuvura. Intera y'icyizere ntigomba gukoreshwa nkigisimbuza hypothesis nta guhinduka kwinshi. BMI igereranya indangagaciro z'umubiri, CRP igereranya poroteyine C, na GDF-15 igereranya itandukaniro ryo gukura 15.
Kuri baseline, umubare munini w'abarwayi bo mu itsinda rya ponsegromab 200 mg bavuze ko nta kugabanuka kwa appetit; Ugereranije na placebo, abarwayi bo mu matsinda ya ponsegromab 100 mg na 400 mg bavuze ko ubushake bwo kurya bwifashe kuva ku byumweru 12, hiyongereyeho amanota ya FAACT-ACS ya 4.12 na 4.5077. Nta tandukaniro rikomeye ryagaragaye mu manota ya FAACT-ACS hagati ya 200 mg hamwe nitsinda rya placebo.
Bitewe nigihe cyateganijwe cyo kwambara hamwe nibibazo byibikoresho, abarwayi 59 na 68, batanze amakuru kubyerekeranye nimpinduka zimyitozo ngororamubiri hamwe n’ibihe bigenda ugereranije n’ibanze. Muri aba barwayi, ugereranije n'itsinda rya placebo, abarwayi bo mu itsinda rya mg 400 bariyongereye mu bikorwa rusange mu byumweru 12, hiyongeraho iminota 72 y'imyitozo ngororangingo idicaye ku munsi. Hiyongereyeho, itsinda rya mg 400 naryo ryiyongereye mubyerekana imitsi ya skeletale yo mu cyumweru cya 12.
Umubare wibintu bibi byabaye 70% mumatsinda ya ponsegromab, ugereranije na 80% mumatsinda ya placebo, kandi byagaragaye mubarwayi 90% bahabwa imiti igabanya ubukana icyarimwe. Indwara yo kugira isesemi no kuruka yari hasi mu itsinda rya ponsegromab.