很多癌友都對免疫療法抱持的很大的希望,包括我在內也是,持續都在收集相關資訊。為了讓癌友更了解免疫療法,Cincia整理了免疫療法懶人包給大家參考。

(所有資訊都是參考網路、期刊而來的,恕不標明參考文獻,因為Cincia不想再花時間去一篇篇找出來啦!又不是在寫論文XDDDD)


對抗可怕的癌症,過去醫界常用四種方法:手術、化療、放療、標靶治療。如今,第五種療法「免疫療法」被視為癌症患者的新救星,由於免疫療法藥物的作用是活化免疫細胞而非殺死癌細胞,因此具有可以治療多種癌症的特性,最大的特色是可單獨使用及治療後若有效則不再復發。

何謂癌症免疫療法?

癌症免疫療法可粗分為「分子免疫療法」「細胞免疫療法」兩類。

分子免疫療法

分子免疫療法也稱作藥物免疫療法,利用單株抗體與T細胞上的特殊分子(CTLA-4PD-1)結合,以去除腫瘤細胞與之牽制,而讓T細胞發揮殺死癌細胞的功能,這些藥物稱為免疫檢查點抑制劑(checkpoint inhibitor),這幾年免疫療法之所以成功成為熱門話題,就是因為初步的臨床試驗發現這些免疫檢查點抑制劑可以在許多不同的癌症中發揮殺死癌細胞的功能,比起化學療法療效更佳,存活期更長,成為癌症病人的新希望。

簡單來說,腫瘤會大量分泌嵌住免疫檢查點的物質,壓制本來應該活化的T細胞(或免疫系統);這些會抑制T細胞活化的物質,可能有十種以上,目前找出比較明確的有CTLA-4PD-1兩種。所以若能把這些抑制物質消滅,就能讓免疫系統發揮攻擊腫瘤的功能。

分子免疫療法即是利用單株抗體,抑制掉會壓制T細胞的物質,讓腫瘤沒辦法抑制T細胞,才能發揮T細胞攻擊腫瘤細胞的能力。

國內已核准兩張藥證,適應症都是黑色素細胞瘤,另開放八種不同癌別包括大腸癌、頭頸癌、肝癌、肺癌等,可申請專案進口。

目前全球有3個免疫檢查點抑制劑已上市:

 

藥品學名

商品名

藥廠

藥理作用

1

Pembrolizumab

Keytruda

MSD默克

抗PD-1單株抗體

2

Nivolumab

Opdivo

BMS和小野品

抗PD-1單株抗體

3

Ipilimumab

Yervoy

BMS必治妥施貴寶

抗CTLA-4單株抗體

1. Keytruda

劑量:2mg/kg,每3週一次

費用:12.8萬元/50mg。以50kg算,一次打100mg,要價25.6萬元。

   打6次判定有沒有效果,有效果的話要持續打一年。(一年打17次請自行計算總費用囉)

2. Opdivo

劑量:3mg/kg,每2週一次

費用:233,382元/100mg;47,699元/20mg。以50kg算,一次要打150mg, 約35萬元。

3. Yervoy(益伏)

劑量:1mg/kg,每3週一次,一個療程共注射4次。

費用:20萬元/50mg。以50kg算,一次打50mg,要價20萬元。(現在價格好像有降??)


除了上面的費用,還需支付醫院藥品管理費。

免疫效果平均要2~3個月才會出現,一般是以第二次CT的結果來判定。

免疫療法個體差異甚大,合併使用肺癌仍在早期臨床試驗,各家廠商都有,基本上要求沒有基因突變。

單打PD-1單株抗體:抽煙者比未抽菸者效果好,沒突變比突變好。榮總蔡俊明主任表示,PD-1單株抗體對肺腺癌整體反應率約20%。

Opdivo通過美國FDA的條件對PD-L1的表現程度並沒限定,但Keytruda則有;有研究指出,Keytruda對腫瘤呈現PD-L1陽性的病人反應率(ORR)是40%。

'15年10月,FDA也核准了 Opdivo和Yervoy合併治療黑色素瘤,兩種藥劑合併治療,第一年需要$256,000美金,第二年單用Opdivo費用為15萬美金。

(費用計算: The cost for the initial 12-week phase of the combination is about $141,000, and then $12,500 a month for Opdivo alone, totaling roughly $256,000 if a patient stays on therapy for a year, according to a Bristol-Myers spokeswoman. Subsequent full-year costs of therapy would be about $150,000 for Opdivo alone.)

【可能副作用】

- 一般問題:疲累、貧血、瘙癢、皮疹、噁心、嘔吐、食慾減退、咳嗽、便秘、腹瀉、關節痛、頭痛、肌痛、腹痛、背部疼痛、頭暈、發燒

- 肺部問題:肺炎、呼吸困難、胸痛、咳嗽

- 肝臟問題:肝炎、皮膚或眼白發黃、肝指數異常

- 腎臟問題:腎炎、腎功能衰竭、尿液顏色改變

- 腸道問題:結腸炎、腹瀉

- 甲狀腺、腦下垂體、腎上腺等問題

**若有等級3或4的副作用, 須停止治療

**肝問題需定期抽血檢查相關指數

【治療副作用】

- 類固醇:Hydrocortisone

- 抗過敏藥:Benedryl

- 止痛藥:Tylenol、Paracetamol

- 抗組織胺藥:Chlorphenamine

**臨床試驗的類固醇最多只能用10mg/day

**有的會在免疫治療前,先預防性給藥


細胞免疫療法

抽取自體免疫細胞,在實驗室以藥物或基因轉殖方式,使其增生並認識癌細胞,約2至3周輸回體內,增強免疫力,可與分子免疫療法合併使用,國內仍在臨床試驗階段。

主要培養是以下三種免疫細胞後回輸體內:

1. NK細胞(自然殺手細胞)

2. DC細胞(樹突細胞)

3. T細胞

戰友Caspar在千葉大學醫院做的免疫細胞治療,就是同時施打上述三種免疫細胞。

還有「胜肽疫苗」的免疫細胞治療方式。此方式也是抽取病患的血液檢測HLA類型,然後配對胜肽,再回輸體內。原理是透過胜肽去刺激免疫細胞快速增長,讓大量免疫細胞去攻擊癌細胞。很多戰友去久留米大學醫院參加的實驗計畫,就是屬於此種療法。

此外,近幾年才被改良使用到臨床上的新型細胞療法「CAR-T(Chimeric Antigen Receptor T-Cell Immunotherapy,嵌合抗原受體T細胞免疫療法)」也值得關注。這項治療是培養T細胞,同時再透過改變基因排序的方式與T細胞結合後,再回輸人體體內。目前研究的成果發現,對血癌、淋巴癌、肉瘤類的癌症,效果非常好,但部分受試者的副作用非常大。

CAR-T細胞療法的步驟:

一、由癌症病人身上分離免疫T細胞

二、利用基因工程技術,給T細胞加入一個能辨識腫瘤細胞,同時激活T細胞殺死腫瘤細胞的嵌合抗體後,T細胞變身為強大的CAR-T細胞,不再是普通的T細胞。它具有追蹤導航 (如:GPS) 的功能,隨時尋找癌細胞,並發動自殺性攻擊,最後同歸於盡的去除癌細胞作為。

三、體外大量培養擴增CAR-T細胞,一般來說,一個癌症患者需要數十億到上百億CAR-T細胞 (治療依體重計算)。

四、將擴增的CAR-T細胞回輸病人體內。

五、回輸後,嚴密監控病患身體狀況,因為輸後前幾天可能有不良反應。

【國內開放現況】

之前僅高醫有獲得衛服部許可,針對頭頸癌和肝癌有試驗計畫(主要是培養DC細胞和T細胞打回體內),現在不確定計畫是否持續?

但經過Caspar提案和5,000位戰友&家屬的連署,衛服部即將修法開放細胞免疫療法,各位戰友敬請期待。


【其他參考文章】

癌症免疫療法浪潮 一年330億美元的PD-1抑制劑大海(By Dr. Wesley)

免疫治療的今、昔與未來(By和信醫院胡涵婷醫師)

免疫療法 癌症病人的新希望(By藍弋丰)

CAR-T免疫疗法,治愈癌症不是梦

滅癌細胞治療法(CAR-T細胞療法)發展進展

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  • Michael
  • 免疫療法趕快納入健保,大家的病也趕快好哦。
  • 免疫納入健保,真的還有好長一段路要走,費用太高,真的很難。

    Cincia 於 2016/02/25 10:23 回覆

  • 訪客
  • 希望健保幫忙
    不然只是夢
    窮人需要健保幫忙
    大家才能受惠
  • 要健保負擔,真的很難,只好趕快努力存錢,留著之後買藥。^^"

    Cincia 於 2016/02/25 10:24 回覆

  • Kim
  • 妳應該唸醫科的,寫得太好了!簡單明瞭,感恩受惠!
  • Kim姊太抬舉我了,只是把手邊有的資料整理上去,Andrew兄都說我太懶了。XDDDDD

    Cincia 於 2016/02/25 10:22 回覆

  • David
  • 寫的太棒了 適用症 費用都交代很清楚

    有些問題我並不清楚意思

    >免疫療法個體差異甚大,合併使用肺癌仍在早期臨床試驗,各家廠商都有,基本上要求沒有基因突變。

    癌症或多或少都有基因突變 "要求沒有基因突變"是什麼意思?

    >單打PD-1單株抗體:抽煙者比未抽菸者效果好,沒突變比突變好。

    的確抽煙者比未抽菸者效果好 原因是抽煙者癌細胞突變比未抽菸者多
    我的瞭解是突變越多 免疫系統越容易辨識癌細胞 PD-1治療效果越好
  • 這兩段話都是廖醫師告訴我的,他的意思是
    1.免疫療法試驗計畫很多都要求沒有基因突變的(無EGFR, ALK)
     ->應該是要告訴我我進入計畫的機率不大
    2.效果沒突變比突變好,這也是先前試驗的數據;可能就是因為這樣,所以研究計畫要求受試者沒有基因突變。

    我們個人的理解不一定對阿!畢竟我們都不是專業人士XDDD

    Cincia 於 2016/02/25 11:31 回覆

  • David
  • 補充說明CAR-T

    1) 打入體內CAR-T細胞會持續生殖繁演 因為是基改的T細胞 新生的CAR-T細胞也俱有能辨識癌細胞的能力

    2) 癌症是不斷突變的生命體 像標靶藥一樣 CAR-T細胞會失去效用

    3) CAR-T還在實驗階段 目前美國只有NCI MD Anderson Florida Moffitt Cancer Center等有在進行研究 MD Anderson每月只能處理4位病人 難以普及化 不像免疫檢查點抑制劑 各大醫院都可使用


  • Jason
  • 中國醫藥大學附設醫院也有自體細胞免疫療法,名嘴陳立宏(腦癌四期)在公視節目提及,在榮總開刀放化療後,經中醫大醫院楊文光教授以自體細胞免疫療法治療,已控制(他表示腦癌四期若僅以開刀放化療治療,1年內復發率為95%,1年半內復發率為100%,而他已超過1年半)。
  • 楊文光沒有開門診啊!根本也沒辦法給他看,除非找關係吧!

    Cincia 於 2016/02/25 11:35 回覆

  • 悄悄話
  • Jon
  • BMS 有全球新藥 Expanded Access Program (Compassionate Use), http://www.bms.com/research/Pages/Expanded-Access.aspx

    不知台灣有沒有人試過請醫生申請看看?

    另外,USFDA 2015 11月也核准了 Nivo(Opdivo) 用於轉移性腎臟癌
  • ann88097
  • 謝謝Cincia用心整理分享,讓我了解免疫療法
  • 有幫助就好~開心:)

    Cincia 於 2016/02/26 13:36 回覆

  • may
  • 我有遇到一個病友,她沒有pd-1,但是有一個非常罕見的基因突變,
    她被同意可加入免疫實驗療法,是免疫與化療並用,因為時間關係,
    沒有多聊,所以不知她的效果如何。
    另有一位是肝癌,用過標靶,而後還是復發,現加入免疫實驗,看起來狀況不錯。
    不過,看起來免疫藥物是一種賭注,又得燒很多錢,真是辛苦呀。
    到底要不要試呢?還真令人猶豫。
    船到橋頭自然直,到遇到要抉擇時,再說囉。^_^
  • totoma
  • 嗯! 條列式簡單易懂!
    封你為筆記公主好了!
    嘻嘻!
  • 哈哈~我以前學生時代真的還蠻會做筆記的,哈哈!^^

    Cincia 於 2016/03/03 13:26 回覆

  • David
  • Jon: Compationate use is a great way to get the drug at affordable price. My dad is on a similar program.
    I know some doctors in Taiwan would do it for patients.
  • Jhsu
  • David,

    Much appreciated. Is your dad on BMS program from Taiwan? I would very much like to learn more from your experiences.

    I am on Voltrient (TKI) for more than a year and am thinking of Nivo as next line of treatment.

    Jon
  • 訪客
  • 在台灣免疫治療人體試驗要收費,合理嗎?
    是藥廠不願意在台灣做免費的免疫治療人體試驗嗎?
    不如去日本做免疫治療,還可以散心看風景,既然要花錢那就順便當作旅行。而且在台灣花費的高價錢,還可以去日本當做豪華團旅行。
    我的問題是,在台灣做臨床的免疫治療人體試驗為何要花錢??
    美女,你吃的藥不用錢吧?臨床試驗藥收你錢的時候你還會去做嗎?除非你是富二代。
    台灣的免疫療法臨床人體試驗要病患自己花錢幫藥廠做實驗,請問這是甚麼邏輯?
    請問有神人可以幫忙解答嗎?
  • 不是很懂你的意思?台灣參加試驗計劃也沒在收錢啊!有些藥廠還會給車馬費哩!
    我上面文章的價格是"自費"的價格,不是參加計畫還要付錢。
    參加分子免疫試驗計畫,患者都是不用付錢的;高醫的免疫細胞計畫也沒跟病人收錢。

    Cincia 於 2016/03/03 13:22 回覆

  • David
  • Jon: My dad has melanoma. He is a US resident so he is on a different program.

    It looks like Taiwan is not on the list for Nivolumab yet, possibly because of on-going clinical trials. The "early patient access" program usually starts after the drug has been approved by the country's health authority. Usually the doctors who hosts clinical trials have access to the program, possibly because of his/her experience with the investigational drugs.

    http://www.bms.com/clinical_trials/investigator_sponsored_research/Pages/expanded-access-program.aspx
  • 新莊小剛
  • 謝謝星希亞幫整理,感恩無限。 加油
  • 不會,我也是幫自己整理。:)

    Cincia 於 2016/03/03 11:03 回覆

  • Jhsu
  • David,

    Exactly. I think it takes some initial requests from Taiwan in order to be able to added to the country list, the last item on the list are for the purpose(other indications).

    Outside the US, named patient programs provide controlled, pre-approval access to drugs in response to requests by physicians on behalf of specific, or "named" patients before those medicines are licensed in the patient’s home country.

    RCC always follows melanoma on clinical trial path for the same drug in the US, and much more clinical trials available for patients like us to join than here in Taiwan.

    Jon
  • teresa
  • 妳好棒!看妳的文章真的很正面!要繼續加油喔
  • 謝謝!繼續加油~:)

    Cincia 於 2016/03/03 11:01 回覆

  • 訪客
  • 你整理的非常棒,但費用真的相當高不是一般人吃得起的
  • 感謝誇獎,不過免疫治療應該不是用吃的XDDDD

    Cincia 於 2016/03/03 11:00 回覆

  • Sam Kao
  • 美女~可以幫個忙,姑娘我任職於金融業從沒加入直銷過也沒喜歡過直銷過,或許以後會想了解但僅是基於好奇
    我個父親因為罹患肺癌,在google大神幫我找到你, 謝謝你的版讓我知道肺癌的資訊
    我老爸肺癌4期末,已確診將近一年半,目前正在廖唯昱醫師那裏治療,我基於你的版知道抗癌戰友會,也曾加入那個群組,在那群組因為不知道不可以提到有關葛森任何事項, 就被踢出群組了, 本人不是葛森協會,或葛森互助園的什麼義工,志工之類的會員, 僅是想了解能救我爸爸的資訊而已

    因為喜歡看57健康同學會,從那裹初步得知葛森療法,且在抗癌戰友會再看到有人提到葛森療法。。。因而開始了解更多更多

    試問,我是心疼抗癌戰友看到諸多人因西醫治療而離世,發言請他們慎重了解葛森,因不知道你們版規有限制,我願意不再提及一字有關葛森,本人亦不是直銷會員:什麼美安、美樂家、安麗等。。。。我個人非常排斥直銷。。是否可以幫我復權,因我父親還在化療,想多了解相關事宜

  • 我解除了,你看一下可不可以看到文章?

    Cincia 於 2016/03/04 16:58 回覆

  • Sam Kao
  • 還在pending 中, 我要在此謝謝您

    人美心美像個活菩薩一般以自己抗癌成功的故事,讓我能在那段徬徨無助的痛苦日子能燃起一絲希望,謝謝你的分享,感恩~~
  • 我看到你在社團裡囉!^^

    Cincia 於 2016/03/07 09:37 回覆

  • Sandy
  • Cincia 好佩服妳堅毅ㄉ個性,我也是癌症患者(也在台大)但跟妳是不同癌。是電腦查癌藥資訊"晃"到妳這兒來 發現這裡。妳很有想法 生活ㄉ文章又挺有趣ㄉ。我沒事會多來晃晃呦~
  • 一起加油囉!
    癌後的生活也一樣可以多姿多采喔!^^Y

    Cincia 於 2016/03/07 09:17 回覆

  • Sam Kao
  • 謝謝美女幫我復權,因我爸肺積水的事情能多做更多了解,謝謝
  • 不會~一起加油!!

    Cincia 於 2016/03/13 10:05 回覆

  • Jhsu
  • The big question in the CAR T-cell therapy is whether it can be adopted to treat solid tumors.

    There are several reasons why the CAR T-cell approach faces more obstacles in solid cancers versus blood cancers. Foremost is that there are not many proteins on the surface of cancer cells that are not also found on normal cells. If a target protein is also expressed on normal cells, unleashing CAR T-cells recognizing this target could be homicidal.

    The second problem with CAR T-cell therapy for solid tumors is that, when injected into the blood stream, the modified T-cells may have difficulty reaching the tumor site.
  • David
  • Atezolizumab Improves Survival in Previously Treated NSCLC

    Atezolizumab prolongs overall survival (OS) over that achieved with docetaxel among patients with previously treated non-small cell lung cancer (NSCLC), and improvement was associated with programmed death ligand 1 (PD-L1) expression on tumor cells and tumor-infiltrating immune cells, according to a report from the open-label phase II randomized controlled POPLAR trial published in The Lancet.

    “These data, along with those from other atezolizumab studies in patients with previously treated NSCLC, demonstrate the clinical efficacy and safety of targeting PD-L1 with atezolizumab in this patient population,” the coauthors concluded.

    A total of 142 patients were administered atezolizumab (1200 mg) and 135 patients were administered docetaxel (75 mg/m2) once every 3 weeks. OS in the intention-to-treat population was 12.6 months for atezolizumab versus 9.7 months for docetaxel (hazard ratio [HR] 0.73; 95% CI: 0.53-0.99; P = .04).

    The findings also suggested that PD-L1 expression may predict atezolizumab benefit. “In our exploratory analysis, patients with pre-existing immunity, defined by high T-effector-interferon-γ-associated gene expression, had improved overall survival with atezolizumab,” the coauthors reported.

    Overall, atezolizumab was well-tolerated with lower rates of drug discontinuation compared to docetaxel; 11 (8%) patients in the atezolizumab group discontinued because of adverse events versus 30 (22%) patients in the docetaxel group. Potential immune-mediated adverse events, such as increased aspartate aminotransferase, increased alanine aminotransferase, pneumonitis, colitis, and hepatitis occurred at low frequencies (<5%) in the atezolizumab group and were generally manageable and reversible.

    “A key strength of POPLAR was that this study enrolled patients irrespective of PD-L1 status, which was prospectively assessed on both tumor cells and tumor-infiltrating immune cells,” the authors reported.

    “The exploratory analyses of T-effector and interferon γ gene signature deepens our understanding of mechanisms of response to anti-PD-L1 blockade and provides a starting point for development of future predictive biomarkers for cancer immunotherapies,” they wrote.

    The relatively small number of patients enrolled in the study diminished opportunities for robust subgroup analyses.

    - See more at: http://www.oncotherapynetwork.com/lung-cancer-targets/atezolizumab-improves-survival-previously-treated-nsclc?cid=em.otn.32716&GUID=2EBB6C9B-9060-456B-9F77-F269905CD658&rememberme=1&ts=27032016#sthash.8cpIT17V.dpuf
  • David
  • 化療可以激起一部份人對癌症的免疫反應是確定的
    但是需要anti PD1才能讓免疫反應持續下去
    清除體內的癌細胞

    The role of the lymphocytic infiltrate in breast cancer

    Over the past few decades, a growing body of evidence has emerged demonstrating that the immune system participates both in tumor development (via chronic inflammation orchestrated by the innate immune system) and in tumor elimination and control (through the actions of the adaptive immune system) [4]. The presence of tumor-infiltrating lymphocytes (TILs) is observed in some breast tumors and has been reported to be a good prognosis feature for some forms of the disease [5–7], particularly for rapidly proliferating tumors correlating with negative axillary nodal status, smaller tumor size, and lower grade [6]. Similarly, TIL count has been associated with better survival in patients with estrogen receptor (ER)-negative tumors [8, 9]. Also, TILs have been negatively correlated with patient’s age at diagnosis [8, 9]. Recently, TILs have emerged as a potential prognostic and predictive marker in BC, especially in the triple-negative (TN) and HER2-positive subtypes. Loi and colleagues [10] have evaluated the predictive value of TIL in 935 patients in the FinHER (Finland Herceptin) trial. Among the 134 TN patients receiving docetaxel and fluorouracil/epirubicin/cyclophosphamide (FEC) or vinorelbine and FEC, the 3-year recurrence-free survival was 90% in the case of extensive lymphocyte infiltrate (intratumoral or stromal TIL >30%) versus 66% in the case of non-extensive lymphocyte infiltrate (P = 0.007). In locally advanced BC treated with neoadjuvant chemotherapy, the presence of TILs in the primary biopsy predicts pathologic complete response [9]. In this study, TIL was composed of both CD3+ and CD20+ cells. The same group has recently evaluated the prognostic and predictive value of TILs in a large cohort of lymph node-positive early-BC patients prospectively randomly assigned to receive either high-dose anthracycline-based chemotherapy or a combinatorial regimen involving anthracyclines and docetaxel within the BIG02-98 trial [11]. TILs+ were strongly associated with good prognosis among patients with TN BC, whereas TILs had no prognostic value among patients with HER2+ BC. However, TILs+ were associated with improved therapeutic responses to high-dose anthracyclines in patients with HER2+ BC [11]. Interestingly, Demaria and colleagues [12] have reported that taxane-based primary chemotherapy converted 7 out of 21 breast tumors from TIL− to TIL+ and that the post-chemotherapy TIL+ status was associated with an improved clinical response. Furthermore, Ladoire and colleagues [13] have reported that neoadjuvant chemotherapy increased the CD8+ infiltration in the tumor. This post-treatment infiltration is associated with an improved outcome. It is worthy to highlight that one of the proposed mechanisms of action of chemotherapy is the induction of an anti-tumoral immune response. The group led by Zitvogel [14] has reported that cytotoxic agents, including anthracyclines, oxaliplatin, and radiation therapy, induce immunogenic cell death through high-mobility-group box 1 release. In this model, chemotherapy kills cancer cells. This modality of cell death itself induces signal danger and tumor-specific T-cell response. Interestingly, the induction of T-cell response is highly heterogeneous according to individuals and tumor characteristics. This inter-individual variability in the ability of chemotherapy to induce immune response could explain why chemotherapy is not working the same in all patients.

    http://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr3620
  • nini
  • 請問您是否有聽過免疫療法對於睪丸癌有相關的療效病例嗎?真希望大家都可以健康…
  • 我個人沒聽過相關的病例。建議你到FB抗癌戰友會詢問看看喔!

    Cincia 於 2016/04/06 17:56 回覆

  • David
  • 解釋一下 根據一項報告 原本沒有癌症免疫反應的人 (ie. 沒有滲透腫瘤的T細胞 TIL)
    一部份(1/3)的人在使用taxane化療後產生癌症免疫反應(ie. 有滲透腫瘤的T細胞 TIL)

    Interestingly, Demaria and colleagues [12] have reported that taxane-based primary chemotherapy converted 7 out of 21 breast tumors from TIL− to TIL+ and that the post-chemotherapy TIL+ status was associated with an improved clinical response. Furthermore, Ladoire and colleagues [13] have reported that neoadjuvant chemotherapy increased the CD8+ infiltration in the tumor. This post-treatment infiltration is associated with an improved outcome.

    因為有沒有TIL 與病人預後有很大關係 (有TIL 病人預後較佳)
    同樣化療藥每個人反應不一樣 有人打化療後不再復發 有人會復發
    也許跟病人打化療後有沒有產生癌症免疫反應有關

    In this model, chemotherapy kills cancer cells. This modality of cell death itself induces signal danger and tumor-specific T-cell response. Interestingly, the induction of T-cell response is highly heterogeneous according to individuals and tumor characteristics. This inter-individual variability in the ability of chemotherapy to induce immune response could explain why chemotherapy is not working the same in all patients.

    很可惜的 即使醫師都知道 有沒有TIL 與病人預後有很大關係
    這項指標至今還沒有納入病人治療的一部份
    醫師不理會這項指標 不強調激起病人癌症免疫反應的重要性
    實在是當今癌症治療的一大遺憾

    In BC, recent evidence has demonstrated that immune-related factors play an important role in defining patient prognosis and their response to treatment. These include the extent of lymphocyte infiltration in tumor tissue and a class of gene expression signatures, both of which have the potential to more precisely define patients’ clinical evolution and identify patient subgroups with different sensitivities to standard treatments. Despite these new insights, clinicians still rely primarily on classic clinical-pathological features such as tumor size and lymph node involvement for daily patient management, and it is difficult to see how these parameters may be implemented in the clinic in the future.
  • David
  • 林先生非常厭惡化療 林先生可能不知道有可能是化療救了林先生
    有可能林先生在化療後產生抗癌症的免疫反應(TIL+)
    其實林先生的案例與許達夫很像
    許達夫也是做了化療後就什麼都不做的
    絕對不是甩手功和天仙液救了許達夫


  • 訪客
  • 林先生故事人
    36訪客說的沒錯^_^
    跟我同期也是聽許達夫什麼甩手功
    甩手甩到天堂去了
    我只是怪物就連醫生也不可思議
    我也不會用什麼方法讓自己出風頭
    只是化療很多人都很痛苦
    我化療是沒什麼感覺
    只是身在期中感受很深
    看到化療到腎臟壞了
    氣官都慢慢的衰竭
    你知道嗎
    當你戰友這禮拜還在下禮拜上天堂
    那種心情
  • 我覺得運動真的有幫助,不管是甩手功還是什麼的,都可以增強免疫力。
    林先生你不是也都有在運動嗎?
    我這幾年參加的告別式比婚禮多太多了,已經可以坦然面對這種悲傷和無奈,只能自己繼續加油!

    Cincia 於 2016/04/06 17:47 回覆

  • David
  • 有人問我:
    那要怎麼樣知道有沒有產生癌症免疫反應呢?

    我說:
    經過手術和化放療後 體內沒有腫瘤 很難知道有沒有產生癌症免疫反應
    只有等癌症復發擴散後才知道沒有免疫反應 
    就算有免疫反應 沒有anti PD1最後還是很可能會被癌症所壓抑 (ie. 所有活化的T細胞戰死沙場)
    所以我爸UCLA醫生根本不管我爸有沒有免疫反應 有沒有TIL 腫瘤有沒有PDL1
    只要沒有其它地方沒有出現癌症  就持續打anti PD1  
    只有anti PD1能夠讓T細胞在惡劣的腫瘤微環境下存活
  • David
  • 提醒一下 化療藥品有許多種 作用機制大不相同
    這裡提到的能激起癌症免疫反應的taxane-based 化療藥品
    包括 太平洋紫杉醇paclitaxel 和 歐洲紫杉醇 docetaxel

    Taxanes, such as paclitaxel and docetaxel, are widely prescribed chemotherapeutic drugs
  • David
  • #37 林先生 我完全能瞭解你的心情
  • 訪客
  • 親愛的星希亞,我剛看到樓上提葛森結果被鎖,我有寄信問您類似的問題,不知道您有收到嗎?因為我不大會用電腦,所以不知有否寄出去,還是有收到但是是會被鎖的問題所以美女不理我了。我是sh59.
  • 提葛森被封鎖??我沒有封鎖什麼訊息啊!只會刪除廣告或人身攻擊而已耶!
    e-mail我也沒收到,你要不要再寄一次啊?cincia0816gmail .com

    Cincia 於 2016/04/06 17:49 回覆

  • 訪客J
  • David,

    我是NSCLC病患,完成四次MK免疫治療,是前幾個月讀到您的新知讓我有信心的,想請教令尊有無持續肺積水的副作用呢?
  • David
  • 我爸是黑色素瘤 所以沒有肺積水的問題

    我有位朋友 打Opdivo兩次後出現大量肺積水
    造成呼吸困難 停了3個月
    再回來打Opdivo時 沒有再出現肺積水
    因為肺腫瘤發炎也會造成積水
    所以可能不是Opdivo的副作用

    我查Keytruda官網 只有少數(>2%)有肺積水(pleural effusion)的問題

    肺發炎減緩 積水應該會停止
    希望你可以堅持下去

    KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients with NSCLC. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in 2% or more of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).
  • 感謝David分享。

    Cincia 於 2016/04/06 17:50 回覆

  • 訪客J
  • David,

    謝謝您的鼓勵與分享,目前使用少量類固醇,肺積水已減少2/3, 其他副作用不甚明顯。

    (也要多謝Cincia!)
  • David
  • 腫瘤是如何抑制免疫反應的?

    免疫系統有起動免疫反應的機制
    自然也有抑制免疫反應的機制
    免疫系統負責抑制免疫反應的主要成員是 調節型T細胞(regulatory T cell, or Treg)
    許多腫瘤都可以發現 Treg聚集
    腫瘤越大 Treg越多 抑制免疫反應的力量越強
    腫瘤微環境還有其他抑制免疫反應免疫細胞像是
    tumor associated DC 樹突細胞, Myeloid-derived Suppressor Cells (MDSC),
    tumor associated macrophage (巨噬細胞)
    但是 Treg還是腫瘤抑制免疫反應的主力
  • David
  • 調節型T細胞 與癌症預後
    許多研究發現 腫瘤附近 調節型T細胞 聚集越多 病人的預後越差
    此外許多癌症 調節型T細胞的數量與腫瘤擴散正相關

    Furthermore, there exists a strong correlation between tumour progression and
    Tregs, with increased numbers or frequency of Tregs associated
    with poor prognosis in a variety of cancers, including
    ovarian [30], breast [53], non-small cell lung [54], hepatocellular
    [55], renal cell [40,56], pancreatic [57], gastric [58] and cervical [59] carcinomas.

    之前提到的 TIL的數量越多 病人的預後越好
    真正的情況是TIL和Treg的比率 決定病人的預後

    While an abundance of TILs was proposed initially to correlate with favourable
    prognosis [50], it is now recognized that in many instances
    it is rather the balance between Teff and Treg populations that
    determines disease outcome [2,51,52].

    所以我一直覺得很遺憾 現代醫學還是用各種手段對殺癌症趕盡殺絕
    真正問題還是免疫系統


    Source:
    http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2249.2012.04657.x/pdf
  • David
  • HDAC Inhibitors Enhance Immunotherapy Efficacy in Lung Cancer

    April 04, 2016

    Histone deacetylase (HDAC) inhibitors like romidepsin might improve the efficacy of programmed cell death-1 (PD-1) blockade in lung cancer, suggest preclinical findings reported in the journal Clinical Cancer Research.

    Most lung cancer patients’ tumors do not respond to immune checkpoint blockade agents like those that target PD-1. One possible mechanism underlying tumor resistance to PD-1 blockade is the failure of sufficient numbers of T cells to infiltrate tumor tissue.

    Hypothesizing that upregulating T-cell chemokine expression and thereby T-cell infiltration of tumors would improve PD-1 blockade’s efficacy against lung tumors, the research team went hunting for FDA-approved oncology agents that induce chemokine expression. Screening 97 approved agents, they found one class that did: HDAC inhibitors.

    The HDAC-inhibiting agent romidepsin significantly increased T-cell tumor infiltration and impacted lung tumor growth in mouse models, the team reported—and when romidepsin was subsequently combined with PD-1 blockade in several lung tumor models, the combination showed greater antitumor activity than either agent on its own.

    “These results suggest that combination of HDAC inhibitors with PD-1 blockade represent a promising strategy for lung cancer treatment,” said senior study author Amer A. Beg, PhD, of the Moffitt Cancer Center’s Immunology Program, in a news release.

    Romidepsin and other HDAC inhibitors have already been approved by the FDA for use against lymphoma and other hematologic cancers, Dr. Beg noted.

    The combination will next be tested in several clinical trials, including a study of patients diagnosed with non-small cell lung cancer (NSCLC) at Moffitt Cancer Center.

    - See more at: http://www.oncotherapynetwork.com/lung-cancer-targets/hdac-inhibitors-enhance-immunotherapy-efficacy-lung-cancer?GUID=2EBB6C9B-9060-456B-9F77-F269905CD658&rememberme=1&ts=08042016#sthash.Ib4NM8kX.dpuf
  • David
  • Sean Parker sets up $250 million cancer immunotherapy collaboration

    By Deena Beasley
    April 13, 2016

    (Reuters) - A $250 million grant from Silicon Valley billionaire Sean Parker, announced on Wednesday, aims to speed development of more effective cancer treatments by fostering collaboration among leading researchers in the field.

    The Parker Institute for Cancer Immunotherapy will include over 40 laboratories and more than 300 researchers from six key cancer centers: New York's Memorial Sloan Kettering, Stanford Medicine, the University of California, Los Angeles, the University of California, San Francisco, Houston's University of Texas MD Anderson and the University of Pennsylvania in Philadelphia.

    "Any breakthrough made at one center is immediately available to another center without any kind of IP (intellectual property) entanglements or bureaucracy," Parker, the co-founder of music-sharing website Napster and the first president of Facebook, told Reuters in an interview.

    The institute will focus on the emerging field of cancer immunotherapy, which harnesses the body's immune system to fight cancer cells.

    Recently approved drugs such as Yervoy and Opdivo from Bristol Myers Squibb Co and Merck & Co Inc's Keytruda have helped some patients sustain remission. But those first-generation therapies do not work for everyone, and scientists are trying to understand how to make them more effective.

    "Very little progress has been made over the last several decades," Parker said, referring to cancer drug research. "Average life expectancy has only increased three to six months with some of these drugs that cost billions to develop."

    THREE KEY RESEARCH AREAS

    The institute has identified three key areas of research - modifying a patient's own immune system T-cells to target a tumor; studying ways to boost patient response to current immunotherapy drugs; and research to identify other novel targets to attack a tumor.

    Parker said the current system of cancer drug development discouraged the kinds of risk-taking that could lead to a major breakthrough.

    The new institute "is paradigm shifting," said Dr. Jedd Wolchok, chief of the melanoma and immunotherapeutics unit at Memorial Sloan Kettering Cancer Center.

    He said it would alleviate the need for scientists to secure grants, which he said took up at least 30 percent of his time, foster collaboration among accomplished scientists and provide access to the newest information processing and data technology.

    "I have no doubt this will allow us to make progress, and to make it much more quickly," Wolchok said.

    The Parker Institute aims to ensure members can easily share research discoveries and tools, as well as jointly conduct clinical trials with standardized data collection and operations.

    Parker said the aim was to maximize the return on investment by holding off on licensing deals until later in the research process, or even after a drug has been approved by regulators. Any profits would be funneled back into the institute.

    Patented discoveries made by the cancer center researchers will be shared 50-50 with the institute. A committee with members from each cancer center as well as representatives of the Parker Institute will review potential licensing deals. Jeff Bluestone, a professor at UCSF and an early researcher of immunotherapy, was appointed president of the Parker Institute.

    Parker credited his late friend Laura Ziskin, a Hollywood producer known for such films as “Pretty Woman” and founder of Stand Up To Cancer, with raising his awareness of the need to overhaul cancer research. She died of the disease in 2011.

    "Losing Laura transformed me," he said.

    (Reporting by Deena Beasley in Los Angeles; Editing by Peter Cooney)
  • 訪客
  • 是ipilimumab哦!
  • 感謝~已修正!

    Cincia 於 2016/08/16 18:08 回覆

  • Benyan  Liu
  • 我是10月12日在台北市仁愛醫院確診為第 4 期肺腺癌的肺泡癌,可是我除了走路會喘外(也不會很嚴重,血氧92),沒有其他症狀。我72歲,退休後,喜歡拍攝野鳥,已經拍了七年。今年六月去龍洞拍攝游隼時,爬山喘到不行,才由心臟科看到胸腔科,沒想到竟然中獎。當時彷彿眼前一片黑。幸好看到星希亞的部落格,讓我燃起了希望。感謝妳。

    我的主治醫師是腫瘤科的鄭企峰,見到我面第一件事,就是把手機號碼寫給我,說隨時可打電話給他,他是 7-11。隨後安排我在10月13-14日住院,完成骨骼掃瞄、PET/CT、頭部MRI,已知道骨骼沒問題。10月20日去看報告,和家人一起討論治療計畫。

    我很希望能成為妳的戰友,大家共同來抗癌。
  • 我想大哥身體的底子應該沒問題,後續治療會一切順利的,有什麼問題都可以來這裡或是加入FB的"抗癌戰友會",大家一起討論,加油!

    ps. 你的主治醫師真的很了不起,願意隨時接病人的電話;坦白說這樣對醫師本身很辛苦,完全沒有Off-job的時間,如果病人都很理性的還不打緊,就怕碰到過度緊張的病人,稍微一有不舒服馬上找醫生,也不管白天或黑夜,這樣醫師就太累了啦!

    Cincia 於 2016/10/18 09:27 回覆

  • Benyan  Liu
  • 感謝星希亞,我已經申請加入"抗癌戰友會" FB,我的 FB 也邀請您加朋友,請您來看看我拍的野鳥。謝謝。如果我拍的野鳥照片,有助於您的Blog 或 FB,我願意無條件提供。我拍台灣野鳥,就只是個人樂趣而已。
  • Benyan兄,謝謝你~你拍的照片超讚的啦!
    我想問一下,你有拍過野雁排V字形飛翔的照片嗎?目前戰友會的照片是網路抓的。^^
    有什麼治療上的問題歡迎隨時提出討論,放寬心,繼續開心過每一天吧!

    Cincia 於 2016/10/19 12:57 回覆

  • Benyan  Liu
  • 我有很多野鳥群飛的照片,琵嘴鴨、黑面琵鷺、舊金山的加拿大雁,以及北海道釧路濕地音羽橋的丹頂鶴。您到我的FB去找看看,喜歡那張,我就把同組照片寄給您選用。琵嘴鴨+滿月的那張,是PS的,用於賀節。原圖是傍晚時分拍的,背景是晚霞,拍於鰲鼓濕地。我的FB只開放給朋友,我已邀請您加好友。
    您來瀏覽我的FB,是我的榮幸。您的 Blog 帶給我正向力量,讓我有信心可以再度扛12公斤的大炮鏡頭,去拍野鳥。謝謝您,功德無量!
    我姓劉,您叫我老劉、劉大哥都OK。敬祝晚安!
  • 劉大哥真的拍得很棒,我後續如果有需要會跟你說,就不跟你客氣了。^^
    ps. FB有加你好友了。

    Cincia 於 2016/10/28 09:11 回覆

  • 悄悄話
  • Mandy Chi
  • 星希亞您好:我爸腎上皮細胞癌第四期,因已末期,想試免疫療法,問過醫師,他說這要長期打,否則易有再復發可能.....謝謝您提供我免疫療法相關訊息,我申請FB抗癌戰友會,可否讓我加入,跟大家一起討論 謝謝!
  • FB抗癌戰友會直接申請即可,管理員會審核的。^^
    希望令尊後續治療一切順利。

    Cincia 於 2016/12/21 16:54 回覆

  • andydrc1
  • 您好,偶然看到這裏,先說聲謝謝!
    能否請問: 我姐姐一直在榮總做化療(肺腺癌),但最近精神不是很好,腦部也會轉移。現知道台灣已通過免疫療法,本來想做Keytruda,但看電視有提到細胞免疫療法;因為自己知道有限,但覺得好像細胞免疫療法會更有效果,但網路看了半天,就是不知道台灣(我住台北)現在有那家醫院有在做這項呢? 可否告知,不勝感激!
  • 細胞免疫療法大醫院應該只有高醫林成龍醫師那邊有在做,可以去諮詢看看。

    Cincia 於 2017/01/13 10:20 回覆

  • andydrc1
  • 您好,非常感謝您告知的資訊! 感恩! 非常謝謝您!
  • ^__^

    Cincia 於 2017/01/19 09:51 回覆

  • 阿豬
  • 免疫療法今年應該會有進展。每月薬費約20萬元。台大胸腔內科余忠仁教授有做臨床研究。因內人罹肺腺癌轉肋膜現已做完6次化療,再來打小針。我也一直注意免疫療法。大家加油。謝謝星希亞帶領戰友走艱辛之路。
  • 尊夫人是余主任的病人嗎?
    希望免疫藥物對有基因突變的病患效果可以提升,一起加油喔!

    Cincia 於 2017/01/19 09:53 回覆

  • 阿豬
  • 星友平安:內人5月底經胸外陳晉興醫師胸鏡摘除右上及下肺兩顆腫瘤約3公分,告知轉肋膜。後交化療 主任林宗哲醫師治療4次。10月初給李章銘做光動力手術。休養2個月,元月再做2次化療打大針。至今,所以沒掛到余醫師,只是網路都有他參與研究的訊息。謝謝
  • 了解~希望尊夫人後續治療一切順利,一起加油喔!^_^

    Cincia 於 2017/01/20 14:43 回覆

  • CJ
  • 非常感謝您整理的資料,幫助很大!
  • ^_^

    Cincia 於 2017/01/20 14:41 回覆

  • 胖胖
  • 婆婆久咳以為感冒 到院檢查發現肺腺癌第四期 沒有基因突變 有積水 現在不知要做化療好 還是參加臨床試驗免疫治療 不知如何 能建議嗎
  • 你婆婆身體狀況如何?免疫需要一段時間才有效果,這段時間可能病情會有惡化的風險。
    如果我的身體很好,癌症症狀也不是太明顯,我會優先選擇免疫療法。

    Cincia 於 2017/03/02 18:19 回覆

  • orlando000000
  • 晚安,家母今年2月底被評估為四期肺癌,可原發病灶之肺葉已進行手術切除後才發現腦部轉移,因EGFR及ALK基因檢測皆未突變,所以繼續化療加放療控制,想請問各位病友有哪些醫院的醫師目前有在進行靶向藥物或免疫治療研究計畫的呢?
  • 藥物試驗計畫可以在這裡查詢喔!
    http://www1.cde.org.tw/ct_taiwan/

    Cincia 於 2017/03/20 18:12 回覆

  • 訪客
  • 可查健康醫療網
  • 訪客
  • 我媽媽肺腺癌還有腎臟可以用免疫療法嗎?
  • 是有移轉腎臟嗎?

    Cincia 於 2017/04/06 22:17 回覆

  • 訪客ting
  • 拜託各位朋友幫忙回應
  • 你是#64的訪客嗎?

    Cincia 於 2017/04/06 22:18 回覆

  • 阿堯
  • 另外再請問您CoQ10及硒酵母在哪裡有得買?什麼品牌?感謝您回復
  • 我blog文章都有連結,請爬文一下。^_^

    Cincia 於 2017/05/30 10:01 回覆

  • 訪客
  • 免疫細胞療法是適用於所有癌症嗎?
  • 照原理來講應該是,但詳細還是要請教相關研究的醫師喔!

    Cincia 於 2017/07/12 06:35 回覆

  • a
  • 免疫療法趕快納入健保+1
  • 訪客
  • 因緣際會看到這篇文章
    淺顯易懂,更鼓勵戰友的好心腸

    讓我很是感動

    加油,雖然我目前沒有得癌,但還是為大家加油。穩穩度過難關。
    加油加油
  • :)

    Cincia 於 2017/11/13 14:31 回覆

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