Cachexia yog ib qho kab mob uas tshwm sim los ntawm kev poob phaus, cov leeg nqaij thiab cov nqaij adipose atrophy, thiab cov kab mob hauv lub cev. Cachexia yog ib qho teeb meem loj thiab ua rau tuag rau cov neeg mob qog noj ntshav. Nws kwv yees tias qhov tshwm sim ntawm cachexia hauv cov neeg mob qog noj ntshav tuaj yeem ncav cuag 25% txog 70%, thiab kwv yees li 9 lab tus tib neeg thoob ntiaj teb raug kev txom nyem los ntawm cachexia txhua xyoo, 80% ntawm cov neeg uas xav tias yuav tuag hauv ib xyoos ntawm kev kuaj mob. Tsis tas li ntawd, cachexia cuam tshuam rau tus neeg mob lub neej zoo (QOL) thiab ua rau muaj kev cuam tshuam txog kev kho mob hnyav.
Kev cuam tshuam zoo ntawm cachexia yog qhov tseem ceeb rau kev txhim kho lub neej zoo thiab kev cia siab ntawm cov neeg mob qog noj ntshav. Txawm li cas los xij, txawm tias qee qhov kev nce qib hauv kev kawm txog cov txheej txheem pathophysiological ntawm cachexia, ntau cov tshuaj tsim los ntawm cov txheej txheem ua tau tsuas yog qee qhov ua tau zoo lossis tsis muaj txiaj ntsig. Tam sim no tsis muaj kev kho mob uas tau pom zoo los ntawm US Food and Drug Administration (FDA).
Cachexia (khoom noj khoom haus) feem ntau tshwm sim hauv cov neeg mob uas muaj ntau hom mob qog noj ntshav, feem ntau ua rau poob phaus, cov leeg nqaij nkim, txo lub neej tsis zoo, ua haujlwm tsis zoo, thiab muaj sia nyob luv. Raws li cov qauv kev pom zoo thoob ntiaj teb, qhov no multifactorial syndrome yog txhais tau tias yog lub cev qhov hnyav (BMI, qhov hnyav [kg] faib los ntawm qhov siab [m] squared) tsawg dua 20 lossis, hauv cov neeg mob uas muaj sarcopenia, qhov hnyav poob ntau dua 5% hauv rau lub hlis, lossis poob qis dua 2%. Tam sim no, tsis muaj cov tshuaj tau pom zoo hauv Tebchaws Meskas thiab Europe tshwj xeeb rau kev kho mob qog noj ntshav cachexia, ua rau muaj kev xaiv kho mob tsawg.
Cov lus qhia tsis ntev los no tau pom zoo kom noj tshuaj tsawg olanzapine txhawm rau txhim kho qab los noj mov thiab qhov hnyav hauv cov neeg mob qog noj ntshav siab ntau yog raws li cov txiaj ntsig ntawm ib qho kev tshawb fawb hauv ib lub chaw. Ntxiv rau qhov no, siv sijhawm luv luv ntawm progesterone analogues lossis glucocorticoids tuaj yeem muab cov txiaj ntsig tsawg, tab sis muaj kev pheej hmoo ntawm kev phiv tsis zoo (xws li kev siv progesterone cuam tshuam nrog cov xwm txheej thromboembolic). Kev sim tshuaj ntawm lwm cov tshuaj tau ua tsis tiav los ua kom pom qhov ua tau zoo txaus los yeej tau txais kev pom zoo. Txawm hais tias anamorine (qhov ncauj version ntawm kev loj hlob hormone tso tawm peptides) tau pom zoo hauv Nyij Pooj rau kev kho mob cancer cachexia, cov tshuaj tsuas yog nce lub cev muaj pes tsawg leeg rau qee qhov, tsis txhim kho tuav lub zog, thiab thaum kawg tsis tau pom zoo los ntawm US Food and Drug Administration (FDA). Muaj qhov xav tau ceev ceev kom muaj kev nyab xeeb, muaj txiaj ntsig zoo thiab tsom mus rau kev kho mob qog noj ntshav cachexia.
Kev loj hlob sib txawv 15 (GDF-15) yog ib qho kev ntxhov siab vim cytokine uas khi rau glia-derived neurotrophic factor family receptor alpha-like protein (GFRAL) hauv lub hlwb tom qab. GDF-15-GFRAL txoj hauv kev tau raug txheeb xyuas tias yog tus tswj hwm loj ntawm kev noj qab haus huv thiab kev hnyav, thiab ua lub luag haujlwm hauv cov kab mob ntawm cachexia. Hauv cov qauv tsiaj, GDF-15 tuaj yeem ua rau cachexia, thiab inhibition ntawm GDF-15 tuaj yeem txo cov tsos mob no. Tsis tas li ntawd, nce qib ntawm GDF-15 hauv cov neeg mob qog noj ntshav tau cuam tshuam nrog lub cev qhov hnyav thiab cov leeg pob txha, tsis muaj zog, thiab ua kom muaj sia nyob luv, txo qis tus nqi ntawm GDF-15 raws li lub hom phiaj kho mob.
ponsegromab (PF-06946860) yog ib qho kev xaiv zoo rau tib neeg monoclonal antibody muaj peev xwm los khi rau kev ncig GDF-15, yog li inhibiting nws kev cuam tshuam nrog GFRAL receptor. Nyob rau hauv me me qhib-label theem 1b sim, 10 cov neeg mob uas mob qog noj ntshav cachexia thiab nce circulating GDF-15 qib tau kho nrog ponsegromab thiab pom kev txhim kho hauv qhov hnyav, qab los noj mov, thiab lub cev ua si, thaum cov ntshav GDF-15 qib tau inhibited thiab cov xwm txheej tsis zoo. Raws li qhov no, peb tau ua Phase 2 kev sim tshuaj ntsuam xyuas kev nyab xeeb thiab kev ua tau zoo ntawm ponsegromab hauv cov neeg mob uas muaj mob qog noj ntshav nrog kev nce qib ntawm GDF-15, piv nrog cov placebo, txhawm rau ntsuas qhov kev xav tias GDF-15 yog thawj kab mob ntawm tus kab mob.
Txoj kev tshawb no suav nrog cov neeg laus uas muaj cachexia cuam tshuam nrog mob qog noj ntshav (tsis yog mob qog noj ntshav hauv lub ntsws, mob qog noj ntshav, lossis mob qog noj ntshav) nrog cov ntshav GDF-15 qib tsawg kawg yog 1500 pg / ml, Eastern Tumor Consortium (ECOG) cov qhab nia zoo ntawm ≤3, thiab lub neej expectancy ntawm tsawg kawg yog 4 lub hlis.
Cov neeg mob cuv npe tau raug xaiv kom tau txais 3 koob tshuaj ponsegromab 100 mg, 200 mg, lossis 400 mg, lossis placebo, subcutaneously txhua 4 lub lis piam hauv qhov sib piv ntawm 1: 1: 1. Thawj qhov kawg yog qhov hloov pauv ntawm lub cev qhov hnyav piv rau qhov pib ntawm 12 lub lis piam. Cov ntsiab lus tseem ceeb thib ob yog qhov kev hloov pauv los ntawm lub hauv paus hauv cov qhab nia anorexia cachexia Sub-Scale (FAACT-ACS), qhov kev ntsuam xyuas ntawm kev ua haujlwm kho mob rau anorexia cachexia. Lwm cov ntsiab lus thib ob suav nrog kev mob qog noj ntshav nrog cachexia cov tsos mob ntawm lub chaw muag mis nyuj cov qhab nia, cov kev hloov pauv hauv lub cev thiab cov ntsiab lus nkag mus ntsuas tau siv cov khoom siv kho mob digital hnav. Yam tsawg kawg nkaus hnav lub sij hawm yuav tsum tau teev ua ntej. Kev ntsuam xyuas kev nyab xeeb suav nrog cov xwm txheej tsis zoo thaum kho, kuaj kuaj pom, cov cim tseem ceeb, thiab electrocardiograms. Kev tshawb nrhiav qhov kawg suav nrog cov kev hloov pauv hauv lub lumbar skeletal nqaij index (skeletal nqaij cheeb tsam faib los ntawm qhov siab squared) cuam tshuam nrog cov leeg pob txha.
Tag nrho ntawm 187 tus neeg mob tau raug xaiv kom tau txais ponsegromab 100 mg (46 tus neeg mob), 200 mg (46 tus neeg mob), 400 mg (50 tus neeg mob), lossis placebo (45 tus neeg mob). Xya caum-plaub (40 feem pua) muaj mob qog noj ntshav me me, 59 (32 feem pua) muaj mob qog noj ntshav, thiab 54 (29 feem pua) muaj mob qog noj ntshav.
Qhov sib txawv ntawm 100 mg, 200 mg, thiab 400 mg pawg thiab cov placebo yog 1.22 kg, 1.92 kg, thiab 2.81 kg, ntsig txog.
Daim duab qhia txog qhov kawg ntawm lub cev (hloov lub cev hnyav los ntawm lub hauv paus mus rau 12 lub lis piam) rau cov neeg mob cancer cachexia hauv ponsegromab thiab placebo pawg. Tom qab hloov kho qhov kev pheej hmoo ntawm kev tuag thiab lwm yam xwm txheej tshwm sim, xws li kev cuam tshuam kev kho mob, thawj qhov kawg tau txheeb xyuas los ntawm tus qauv Emax stratified siv lub lim tiam 12 tau los ntawm Bayesian kev sib koom ua ke ntev (sab laug). Cov ntsiab lus tseem ceeb kawg kuj tau txheeb xyuas zoo ib yam, siv kwv yees lub hom phiaj rau kev kho mob tiag tiag, qhov kev soj ntsuam tom qab tag nrho cov xwm txheej sib koom ua ke tau raug txiav (tsim daim duab). Kev ntseeg siab ib ntus (qhia hauv kab lus
Cov nyhuv ntawm 400 mg ponsegromab ntawm lub cev qhov hnyav tau zoo ib yam nyob rau hauv pawg loj preset, suav nrog hom mob qog noj ntshav, ntshav GDF-15 qib quartile, platinum-based chemotherapy raug, BMI, thiab cov kab mob hauv nruab nrog cev. Qhov hnyav hloov tau zoo ib yam nrog GDF-15 inhibition ntawm 12 lub lis piam.
Kev xaiv cov pab pawg tseem ceeb tau ua raws li kev soj ntsuam tom qab-hoc Bayesian kev sib koom ua ke ntev, uas tau ua tom qab kho qhov kev sib tw ntawm kev pheej hmoo ntawm kev tuag raws li kev kwv yees lub hom phiaj ntawm kev kho mob. Kev ntseeg siab yuav tsum tsis txhob siv los ua ib qho kev hloov rau kev ntsuas kev xav tsis muaj ntau yam kev hloov kho. BMI sawv cev rau lub cev qhov Performance index, CRP sawv cev rau C-reactive protein, thiab GDF-15 sawv cev rau kev loj hlob sib txawv 15.
Nyob rau hauv lub hauv paus, ib tug ntau dua ntawm cov neeg mob nyob rau hauv lub ponsegromab 200 mg pab pawg neeg qhia tias tsis muaj kev poob qab los noj mov; Piv nrog rau cov placebo, cov neeg mob hauv ponsegromab 100 mg thiab 400 mg pawg tau tshaj tawm txog kev txhim kho hauv qab los ntawm qhov pib ntawm 12 lub lis piam, nrog kev nce hauv FAACT-ACS cov qhab nia ntawm 4.12 thiab 4.5077, raws li. Tsis muaj qhov sib txawv tseem ceeb hauv FAACT-ACS cov qhab nia nruab nrab ntawm 200 mg pawg thiab pab pawg placebo.
Raws li cov kev cai hnav lub sij hawm ua ntej thiab cov teeb meem ntawm cov cuab yeej, 59 thiab 68 cov neeg mob, raws li, tau muab cov ntaub ntawv ntawm kev hloov pauv ntawm lub cev kev ua si thiab cov ntsiab lus mus rau qhov kawg ntawm lub hauv paus. Ntawm cov neeg mob no, piv rau cov pab pawg placebo, cov neeg mob hauv 400 mg pab pawg muaj kev nce ntxiv hauv kev ua haujlwm tag nrho ntawm 12 lub lis piam, nrog kev nce ntawm 72 feeb ntawm kev ua lub cev tsis muaj zog ib hnub. Tsis tas li ntawd, pawg 400 mg kuj tau nce hauv lumbar skeletal nqaij index ntawm lub lim tiam 12.
Qhov tshwm sim ntawm cov xwm txheej tsis zoo yog 70% hauv pawg ponsegromab, piv nrog 80% hauv pawg placebo, thiab tshwm sim hauv 90% ntawm cov neeg mob uas tau txais kev kho mob qog noj ntshav ib txhij. Qhov tshwm sim ntawm xeev siab thiab ntuav tau qis dua hauv pawg ponsegromab.
Post lub sij hawm: Oct-05-2024