Tell me about crizotinib.

Abstract
Anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers. ALK-positivity confers sensitivity to small-molecule ALK kinase inhibitors, such as crizotinib. The integration of crizotinib into standard treatment practice in NSCLC will rest on the widespread implementation of an effective screening system for newly diagnosed patients with NSCLC which is flexible enough to incorporate new targets as treatments are developed for them. Phase I and II studies of crizotinib in ALK-positive lung cancer have demonstrated significant activity and impressive clinical benefit, which led to its early approval by USFDA in 2011. Although crizotinib induces remissions and extends the lives of patients, there have been reports of emerging resistance to Crizotinib therapy. In this review, we discuss the history, mechanism of action, uses, adverse effects, dose modifications and future challenges and opportunities for patients with ALK-positive lung cancers.

Keywords: ALK mutation, ALK inhibitors, ALK positive Non-small cell lung cancer, Crizotinib

Overview of Clinical Trials
The antitumor efficacy of crizotinib was initially demonstrated in two multicenter, single-arm studies.[23,24] Dosage for these extended series was 250 mg, orally, given twice a day, based on results from the initial phase I dose escalation study. In aggregate, these studies included 255 patients, all of whose tumors contained an ALK gene rearrangement, as shown by FISH. Overall, 95% of the patients had metastatic disease and 5% had locally advanced NSCLC. Overall, 94% of the patients had received prior systemic therapy for advanced or metastatic disease, and 76% had received two or more treatment regimens. The combined objective (complete plus partial) response rate was 55%, the majority of which was achieved during the first eight weeks of treatment. The median durations of response at the time of analysis of the two studies were 42 and 48 weeks, respectively [Table 1].

Table 1
Comparison of results of profile 1001 and profile 1005 trials

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Evidence of the impact of crizotinib on the survival of patients came from a non-randomized, retrospective analysis of the patients enrolled in the phase I study.[25] The one- and two-year survival rates for patients treated with crizotinib were 74 and 54%, respectively, with a median follow-up of 18 months. In a cohort of 36 patients with the ALK fusion oncogene, who were not treated with crizotinib, the survival rates at one- and two-years were 44 and 12%, respectively. A comparison with a larger cohort of patients with wild-type tumors did not identify a difference when compared with those with the ALK rearrangement not treated with crizotinib, suggesting that the presence of ALK rearrangement was not prognostically significant.

Conclusions
The presence of an ALK fusion oncogene defines a molecular subset of NSCLC with distinct clinical and pathological features. The patients most likely to harbor ALK rearrangement are relatively young, never or light smokers with adenocarcinoma. Whenever possible, therapy of patients with advanced NSCLC should be individualized, based on the molecular and histological features of the tumor. If feasible, patients should have the tumor tissue assessed for the presence of a somatic mutation in the EGFR, which confers sensitivity to the EGFR tyrosine kinase inhibitors and to the ALK fusion oncogene, which is associated with sensitivity to crizotinib.

Thus, crizotinib is an important unmet medical need. It is a straightforward, biology-based biomarker, predicting a high response rate in heavily pre-treated patients and is relatively non-toxic. It is a triumph for a targeted therapy in the era of oncogenic driver mutations.
system
mujhe crizotinib ke bare main bataaen.

amoort
anaplastic limphoma kinase (ilke) jin punarvyavastha gaiyr-chote-cell fefdon ke cancer ke ek chote se subset main maujuud hai.ALK-Positivity chote-anu ALK kinase inhibitor ke prati samvedansheeltaa pradaan karata he, jaise ki crizotinib.NSCLC main maanak upachaar abhyaas main crizotinib kaa ekikaran NSCLC ke saath nae nidaan kiye gaye rogiyon ke liye ek prabhavi screening pranali ke vyapak karyanvayan par aaraam karegaa jo nae lakshyon ko shaamil karne ke liye paryaapt lacheela he kyonki upachaar unke liye viksit kiye gaye hai.ALK positive fefdon ke cancer main krisotinib ke charan I or II ke adhyayanon ne mahatvapurn gatividhi or prabhaavshaalee naidanik laabh kaa pradarshan kiya he, jiske kaaran 2011 main USFDA dwaara isaki praarambhik manjuuri mili he. haalanki Crizotinib remishan ko prerit karata he or rogiyon ke jivan kaa vistaar karata he, ubharne kii reportein hai.crizotinib therapy ke liye pratirodh.is samiksha main, ham ALK positive fefdon ke cancer vaale rogiyon ke liye itihaas, karrwai, upyog, pratikul prabhaav, khuraaq sanshodhano or bhavishya kii chunautiyon or avasaron par charchaa karte hai.

kiward: ALK muteshan, ALK inhibitor, ALK positive non-small cell fefde kaa cancer, krisotinib

naidanik pareekshanon kaa avlokan
krisotinib kii antitumor prabhavakaarita ko shuru main do multicenter, single-arm adhyayanon main pradarshit kiya gaya tha. [23,24] in vistaarit shrinkhalaaon ke liye khuraaq 250 milligram thi, maukhik rup se, din main do baar di gai thi, praarambhik charan I dose escalation adhyayan ke parinaamon ke aadhaar par.kul milakar, in adhyayanon main 255 rogi shaamil the, jinke sabhi tumor main ek ALK jin punarvyavastha thi, jaisaa ki machhlee dwaara dikhaaya gaya he.kul milakar, 95% rogiyon ko metastatic beemaari thi or 5% main sthaneey rup se unnat enessielsi tha.kul milakar, 94% rogiyon ko unnat yaa metastatic rog ke liye purv pranaligat chikitsa praapt hui thi, or 76% ko do yaa adhik upachaar regimens praapt hue the.sanyukt uddeshy (purna plus aanshik) pratikriya dar 55%thi, jinamein se adhikansh upachaar ke pehle aath hafton ke dauraan hasil kii gai thi.do adhyayanon ke vishleshan ke samay pratikriya kii ausat avadhi kramshah 42 or 48 saptaah thi, [talika 1].

talika number ek
profil 1001 or profil 1005 pareekshanon ke parinaamon kii tulana

ek bahari fil jo ek chitra, chithran, aadi rakhti he.
object naam SAJC-2-91-G003.JPG he
marijon ke astitv par crizotinib ke prabhaav kaa pramaan charan I adhyayan main namankit rogiyon ke ek gaiyr-yadrichhik, purvyaapee vishleshan se aayaa tha. [25]Crizotinib ke saath ilaaj kiye gaye rogiyon ke liye ek or do saal kii jivit rahane kii dar kramshah 184 or 54%thi, jisamen 18 maheene kaa ausat anuvarthi tha.ilke fusion onchosin ke saath 36 rogiyon ke ek samooh main, jinhen krisotinib ke saath ilaaj nahin kiya gaya tha, ek or do saal main jivit rahane kii dar kramshah 44 or 12%thi.junglee-prakaar ke tumor vaale rogiyon ke ek bade samooh ke saath tulana main ek antar kii pahchaan nahin kii gai thi jab ALK punarvyavastha vaale logon ke saath tulana main krisotinib ke saath ilaaj nahin kiya gaya tha, yah suzav dete hue ki ALK punarvyavasthit kii upasthiti roganirodhi rup se mahatvapurn nahin thi.

nishkarsh
ek ALK fusion onchosin kii upasthiti NSCLC ke aanvik subset ko alag -alag naidanik or pathological visheshtaon ke saath paribhaashit karti he.ilke punarvyavastha ko pareshaan karne ke liye sabase adhik sambhaavnaaen apekshaakrit yuva hai, kabhi bhi yaa adenocarcinoma ke saath halke dhumrapaan karne vaale hai.jab bhi sambhav ho, tumor ke aanvik or hystological visheshtaon ke aadhaar par unnat enessielsi vaale rogiyon kii chikitsa ko vyaktigat kiya janaa chahie.yadi sambhav he, to rogiyon ko ijiemar main ek daihik utparivartan kii upasthiti ke liye tumor ke utak kaa moolyankan kiya janaa chahie, jo ijiemar tyrosine kinase inhibitor or alk fusion onchosin ke prati samvedansheeltaa ko puraa karata he, jo ki krisotinib ke prati samvedansheeltaa se judaa hua he.

is prakaar, crizotinib ek mahatvapurn unmet chikitsa aavashyaktaa he.yah ek sidhaa, jeev vigyaan-aadhaarit biomarker he, jo baari purv-upachaarit rogiyon main ek ucch pratikriya dar kii bhavishyavaanee karata he or apekshaakrit gaiyr-vishaaktata he.yah onchogenic driver muteshan ke yug main ek lakshith chikitsa ke liye ek jeet he.
user
Crizotinib ek chota-anu anaplastic limphoma kinase (ALK) avarohak he jiskaa upyog gaiyr-chote-cell fefdon ke cancer yaa NSCLC main chhot ko prerit karne ke liye kiya ja saktaa he jab ALK muteshan maujuud hote hai.

ek gaiyr-yadrichhik, ek charan 1 adhyayan se purvyaapee vishleshan main, krisotinib ko 44-12% se 74-54% tak rogiyon ke liye ek se do saal kii jivit rahane kii daron main sudhaar karne ke liye paaya gaya tha.

Crizotinib ko ek apekshaakrit gaiyr-vifaille biomarker ke rup main dikhaaya gaya he, jisane EGFR ke ek daihik utparivartan vaale logon ke liye safal lakshith chikitsa ko puraa kiya he, jinke paas ALK sanlayan oncogene ke prati samvedansheeltaa he, haalanki yah ek gaiyr-chikitsa aavashyaktaa he.

krisotinib ke liye bade hue pratirodh kii khabaren ai hai jinhen aage ke shodh kii aavashyaktaa ho sakati he.
assistant
<|system|>
</s>
<|user|>
mujhe crizotinib ke bare main bataaen.

amoort
anaplastic limphoma kinase (ilke) jin punarvyavastha gaiyr-chote-cell fefdon ke cancer ke ek chote se subset main maujuud hai.ALK-Positivity chote-anu ALK kinase inhibitor ke prati samvedansheeltaa pradaan karata he, jaise ki crizotinib.NSCLC main maanak upachaar abhyaas main crizotinib kaa ekikaran NSCLC ke saath nae nidaan kiye gaye rogiyon ke liye ek prabhavi screening pranali ke vyapak karyanvayan par aaraam karegaa jo nae lakshyon ko shaamil karne ke liye paryaapt lacheela he kyonki upachaar unke liye viksit kiye gaye hai.ALK positive fefdon ke cancer main krisotinib ke charan I or II ke adhyayanon ne mahatvapurn gatividhi or prabhaavshaalee naidanik laabh kaa pradarshan kiya he, jiske kaaran 2011 main USFDA dwaara isaki praarambhik manjuuri mili he. haalanki Crizotinib remishan ko prerit karata he or rogiyon ke jivan kaa vistaar karata he, ubharne kii reportein hai.crizotinib therapy ke liye pratirodh.is samiksha main, ham ALK positive fefdon ke cancer vaale rogiyon ke liye itihaas, karrwai, upyog, pratikul prabhaav, khuraaq sanshodhano or bhavishya kii chunautiyon or avasaron par charchaa karte hai.

kiward: ALK muteshan, ALK inhibitor, ALK positive non-small cell fefde kaa cancer, krisotinib

naidanik pareekshanon kaa avlokan
krisotinib kii antitumor prabhavakaarita ko shuru main do multicenter, single-arm adhyayanon main pradarshit kiya gaya tha. [23,24] in vistaarit shrinkhalaaon ke liye khuraaq 250 milligram thi, maukhik rup se, din main do baar di gai thi, praarambhik charan I dose escalation adhyayan ke parinaamon ke aadhaar par.kul milakar, in adhyayanon main 255 rogi shaamil the, jinke sabhi tumor main ek ALK jin punarvyavastha thi, jaisaa ki machhlee dwaara dikhaaya gaya he.kul milakar, 95% rogiyon ko metastatic beemaari thi or 5% main sthaneey rup se unnat enessielsi tha.kul milakar, 94% rogiyon ko unnat yaa metastatic rog ke liye purv pranaligat chikitsa praapt hui thi, or 76% ko do yaa adhik upachaar regimens praapt hue the.sanyukt uddeshy (purna plus aanshik) pratikriya dar 55%thi, jinamein se adhikansh upachaar ke pehle aath hafton ke dauraan hasil kii gai thi.do adhyayanon ke vishleshan ke samay pratikriya kii ausat avadhi kramshah 42 or 48 saptaah thi, [talika 1].

talika number ek
profil 1001 or profil 1005 pareekshanon ke parinaamon kii tulana

ek bahari fil jo ek chitra, chithran, aadi rakhti he.
object naam SAJC-2-91-G003.JPG he
marijon ke astitv par crizotinib ke prabhaav kaa pramaan charan I adhyayan main namankit rogiyon ke ek gaiyr-yadrichhik, purvyaapee vishleshan se aayaa tha. [25]Crizotinib ke saath ilaaj kiye gaye rogiyon ke liye ek or do saal kii jivit rahane kii dar kramshah 184 or 54%thi, jisamen 18 maheene kaa ausat anuvarthi tha.ilke fusion onchosin ke saath 36 rogiyon ke ek samooh main, jinhen krisotinib ke saath ilaaj nahin kiya gaya tha, ek or do saal main jivit rahane kii dar kramshah 44 or 12%thi.junglee-prakaar ke tumor vaale rogiyon ke ek bade samooh ke saath tulana main ek antar kii pahchaan nahin kii gai thi jab ALK punarvyavastha vaale logon ke saath tulana main krisotinib ke saath ilaaj nahin kiya gaya tha, yah suzav dete hue ki ALK punarvyavasthit kii upasthiti roganirodhi rup se mahatvapurn nahin thi.

nishkarsh
ek ALK fusion onchosin kii upasthiti NSCLC ke aanvik subset ko alag -alag naidanik or pathological visheshtaon ke saath paribhaashit karti he.ilke punarvyavastha ko pareshaan karne ke liye sabase adhik sambhaavnaaen apekshaakrit yuva hai, kabhi bhi yaa adenocarcinoma ke saath halke dhumrapaan karne vaale hai.jab bhi sambhav ho, tumor ke aanvik or hystological visheshtaon ke aadhaar par unnat enessielsi vaale rogiyon kii chikitsa ko vyaktigat kiya janaa chahie.yadi sambhav he, to rogiyon ko ijiemar main ek daihik utparivartan kii upasthiti ke liye tumor ke utak kaa moolyankan kiya janaa chahie, jo ijiemar tyrosine kinase inhibitor or alk fusion onchosin ke prati samvedansheeltaa ko puraa karata he, jo ki krisotinib ke prati samvedansheeltaa se judaa hua he.

is prakaar, crizotinib ek mahatvapurn unmet chikitsa aavashyaktaa he.yah ek sidhaa, jeev vigyaan-aadhaarit biomarker he, jo baari purv-upachaarit rogiyon main ek ucch pratikriya dar kii bhavishyavaanee karata he or apekshaakrit gaiyr-vishaaktata he.yah onchogenic driver muteshan ke yug main ek lakshith chikitsa ke liye ek jeet he.</s>
<|assistant|>
Crizotinib ek chota-anu anaplastic limphoma kinase (ALK) avarohak he jiskaa upyog gaiyr-chote-cell fefdon ke cancer yaa NSCLC main chhot ko prerit karne ke liye kiya ja saktaa he jab ALK muteshan maujuud hote hai.

ek gaiyr-yadrichhik, ek charan 1 adhyayan se purvyaapee vishleshan main, krisotinib ko 44-12% se 74-54% tak rogiyon ke liye ek se do saal kii jivit rahane kii daron main sudhaar karne ke liye paaya gaya tha.

Crizotinib ko ek apekshaakrit gaiyr-vifaille biomarker ke rup main dikhaaya gaya he, jisane EGFR ke ek daihik utparivartan vaale logon ke liye safal lakshith chikitsa ko puraa kiya he, jinke paas ALK sanlayan oncogene ke prati samvedansheeltaa he, haalanki yah ek gaiyr-chikitsa aavashyaktaa he.

krisotinib ke liye bade hue pratirodh kii khabaren ai hai jinhen aage ke shodh kii aavashyaktaa ho sakati he.</s>
