一口气看了30页，并把你父亲治疗过程都一一记录下来了，我家也是肺鳞癌骨转、肝转。看了你的治疗贴很感动，你爸有你这样细心体贴的好儿子真有福，祝福你爸，也希望我的家人能够像你爸一样病情得到控制！
老马您好，有个贴，最近没看到憨豆大叔，特搬来咨询一下您，谢谢。
今天，从奇迹网找到了这里，在憨豆大叔的憨氏服务台里面看了一下午，看到了快100页，总共1000多页了，呵呵。受益匪浅。但我仍然希望憨豆大叔以及各位有经验的斑竹和病友能进来指点帮忙，感谢大家。
我父亲，左肺，肺鳞癌，56岁，有长年抽烟史。2010年4月初查出来的，到现在为止，总共做过的治疗有：前后总共化疗了10次，然后放疗了25次（放疗医生说的我父亲的25次的量就相当于别人50次的量），然后今年3月份在左肺位置做了粒子植入。别的治疗就是一些常规的输液，比如消炎，补钾等一些常规治疗了。我父亲从生病到今年春节前，几乎和正常人没什么区别，可就在春节左右，洗澡感冒了一次，然后就生意嘶哑了，一直到现在都未好，而且生意嘶哑程度更严重。检查说是声带被肿瘤压迫固定所致。当时3月份在医院，我父亲的主治医生就建议我父亲做粒子植入，说能控制住肺部的肿瘤，不让它增长或者转移，而且有可能会改善声音的问题。后来就做了，放入了碘粒子79颗。其实直到现在，我父亲都比较后悔那次不该做粒子植入，因为做了之后，我父亲左边胸腔位置就一直感觉胀痛和紧绷感（当然做之前也有疼痛，但比做之后要好，因为当时医生也说了做了粒子也对疼痛有很好的控制作用）。到现在为止，我父亲疼痛一直在加重，现在在重庆市中医院住院，疼痛加重是最近，5月份左右的事了，逐渐加重，之前我父亲在家，完全不能好好的睡觉休息，当时就吃泰勒宁止痛药，后来量越来越大，效果越来越不明显，然后才住院，开了口服的吗啡，以及现在是芬太尼透皮贴3张+口服吗啡早晚各4颗。到现在我父亲肝脏有转移，当时中医院医生建议粒子，我父亲死活不干了，然后8月初增强CT看，肝脏位置有恶化，然后肾上有部分阴影，现在我父亲的主要情况就是:
1.疼痛难忍，主要疼痛位置就是左边的左下腰腹部位置，以及左胸胸腔以及后背对应的肋骨位置。之前是睡着痛，坐起来稍微好点，可奇怪的是现在，就是一个星期以前出现的情况吧，是睡着不痛了，反而坐起来就会很痛，导致现在我父亲吃饭就必须由我母亲喂，之前还偶尔起来到外面走走，现在就一天躺在床上。就是如此大剂量的药，也只有第一天换药的时候感觉好点，然后过了就不行了，中途也还必须补吃泰勒宁止痛。
2.流汗，虚汗的问题。我父亲在前几个月前，就出现右边手到身体流汗，然后左边是干的，医生说是肿瘤导致气血不通，吃中药可以调理，可都调理了3个多月了，还是没什么效果，而且我父亲这两天一直流虚汗，买了参麦饮和虚汗停，感觉都没效果，躺在床上一会就要换毛巾，以及擦汗。
3.到现在，我父亲吃了2瓶易瑞沙，但感觉无效，因为疼痛感和其他感觉都没改善，现在刚给父亲吃特，今天刚好第一天开始吃吧，然后我也看了癌胚原，是185左右，好备吃一段时间看是否有效果。我想问问，吃特的时候，需要注意什么？我父亲现在在中医院，医生有开了很多药在吃，当然也有中药，这些药如何选择？中药可以不喝了吗？还是说分开时间吃？我父亲是每天早上6点，空腹服药。我现在给我父亲买的康力士的小蓟提取物复合胶囊保肝（因为之前听病友介绍吃易瑞沙要配合保肝的药物吃）。
4.貌似憨豆大叔建议的是，如果我父亲吃特有效，需要停一段时间，或者中途换别的药物配合吃，然后等有一点反弹再重吃特，因为如果是一旦吃到耐药再想换别的药物，就比较恼火了，是这样的说法吗？那我想请问我父亲到多久的时机停特稍微好点，停特的时候需要吃别的吗？有什么推荐和建议的吗？中途又到什么时机再换回特才不迟？然后，如果耐药，又怎么办？如果这次我父亲吃特还是无效，那请问还有别的什么办法吗？中医院医生给我说现在没什么积极治疗方法了，而且说我买的药，如果有钱可以试试，但没什么效果，心里真的很难受！
现在看着父亲每天睡在床上，流虚汗不止，消瘦，没什么精神，一天都感觉在睡觉，有时想坐起来看电视或者走几步，就疼痛难忍，心里真的很难受。父亲以前是很健壮的人，身高172，体重160左右，现在只有120斤不到了。哎。年前体重都还有140左右！我真的很希望憨豆大叔以及各位有经验的朋友能帮帮我。
或许问题有点多，语言组织有点杂乱，但真的恳求憨豆大叔和各位朋友的帮忙，在此跪谢了！
我父亲现在过了国庆又身体不行，回医院住起了，然后特罗凯第二瓶已经于前天就吃完了，但貌似没什么用，癌胚原从8月份初开始来的数据，从之前的185左右，到9月7号的414左右，然后前两天查出来已经是700多了，这样已经可以断定特罗凯无用了对吧？现在还有什么可以可以尝试的办法吗？真的很心烦，也感觉无望。连我父亲本来很坚强的人也有点放弃的意思了。现在就是每天躺在医院。现在最主要的就是疼痛，芬太尼透皮贴已经贴了5张了，而且是2天一换。而且口服吗啡是一次4片，一天2次，中途还要吃512来止痛。这个量我想已经是很大很大了，如果不是我父亲身体素质本来好，我想早就受不了了。真的求憨叔给点指示吧。。哎。还可以换什么药试试？易瑞沙吃了2瓶，特罗凯吃了2瓶，肺鳞癌。2年半了。现在就主要是很疼痛。。求求憨叔以及各位朋友了。唑来膦酸每个月 也有打一次。
现在就是人太瘦了，100斤多点的样子了，然后不知道该继续如何治疗？？我都迷茫了。。。疼痛，我父亲都已经准备注射吗啡了，痛得自己都受不了了。。。到底该怎么办
化疗了10次，都用了什么药，效果各如何？
特罗凯应该是无效了，得换方案。
鳞癌好象对EFGR类抑制剂不敏感啊。抗血管生成类的行不行？
老马 发表于 2012-11-5 16:21 static/image/common/back.gif
化疗了10次，都用了什么药，效果各如何？
特罗凯应该是无效了，得换方案。
老马你好，能否方便留个QQ交流，有很多想请教你。谢谢。
你是问化疗用了什么药吗？化疗具体用的药我记不清楚了，如果需要我可以回家去找。另外的治疗就是放疗了25次，做了一次粒子植入放入79颗碘粒子。然后口服易瑞沙2瓶，特罗凯2瓶。然后其他的就是一些消炎或者抑制肿瘤的一些常规治疗。
今天是本次服药周期吃2992的第7天，胃口不错，第4天时腹泻一次。
老马 发表于 2012-11-3 23:05 static/image/common/back.gif
Mechanisms of Trastuzumab resistance in ErbB2-driven breast cancer and newer opportunities to overco ...
英语水平实在有限，大概了解一点。谢谢噢！
A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+ metastatic breast cancer.
Background: Alterations in the PI3K/AKT/mTOR pathway have been implicated in resistance to trastuzumab (T) in HER2+ breast cancer. BEZ235, a potent oral dual PI3K/mTORC1/2 inhibitor, has demonstrated growth inhibition and apoptosis in HER2+ breast cancer models, including those harboring PI3K pathway alterations, and with T resistance. In a Phase I study, BEZ235 was well tolerated as a single agent in pts with advanced solid tumors. The aim of this study was to determine the MTD of BEZ235 in combination with T in pts with T-resistant HER2+ metastatic breast cancer (mBC) with alterations of the PI3K pathway. Methods: Pts with T-resistant HER2+ mBC (i.e. disease progression during adjuvant therapy or metastatic disease on therapy with T) received oral BEZ235 daily, with weekly T (2 mg/kg). Pts were eligible for enrollment if a tumor sample was demonstrated to contain a molecular alteration of PIK3CA and/or PTEN. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Results: As of 23 Sep 2011, 15 of the 19 enrolled pts were evaluable for dose escalation analysis. BEZ235 was evaluated at 3 dose levels: (1) 400 mg/day (3 pts); (2) 600 mg/day (6 pts); (3) 800 mg/day (10 pts), administered either in capsule form (400 mg) or in sachet form (600 mg and 800 mg). The MTD of BEZ235 in combination with T was estimated to be 600 mg/day. Observed DLTs were G3 nausea at 600 mg/day (1 pt), and G3 nausea, G3 fatigue and G3 skin rash (1 pt each) at 800 mg/day. The most frequent G3/4 adverse events (CTCAE v3.0) suspected to be related to study treatment were diarrhea (4 pts) and nausea (2 pts). No deaths related to study treatment occurred. 1 pt with lung and brain metastases had a partial response. 4 pts had disease stabilization for ≥4 cycles (16 weeks), including 1 pt with liver metastases, in whom BEZ235/T treatment resulted in disease stabilization for more than 21 cycles (84 weeks). Conclusions: BEZ235in combination with T demonstrated an acceptable safety profile in pts with HER2+ mBC and PI3K pathway alterations. Following the Bayesian model recommendation, the MTD for BEZ235 in combination with T was estimated to be 600 mg/day. The safety expansion arm is ongoing at the MTD.
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=114&abstractID=96289
本帖最后由 老马 于 2012-11-8 02:16 编辑
英文名 BEZ235 Tosylate
别名 4-quinolin-1-yl]-alpha,alpha-dimethylbenzeneacetonitrile 4-methylbenzenesulfonate
产品名称 BEZ235 对甲苯磺酸盐
Formula:
C30H23N5O
Molecular Weight:
469.54
2-甲基-2-喹啉-1-基]苯基]丙腈
First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors.
Background: The PI3K pathway plays a major role in cancer cell growth and survival, and is frequently aberrantly hyperactivated in tumors. BEZ235 is a potent and highly selective reversible PI3K pathway inhibitor with antiproliferative and apoptotic activity in cancer cells. BEZ235 strongly inhibited activation of downstream effectors (e.g. Akt) and displayed antitumor activity in xenograft models harboring PI3K pathway alterations. In preclinical toxicology studies, BEZ235 treatment was well tolerated. Methods: This phase I, multicenter, open-label, single-agent, dose-escalation, study was conducted in pts with histologically confirmed, advanced, unresectable solid tumors. BEZ235 was administered once daily as a gelatin capsule either fasted or fed (10-1,100 mg) until unacceptable toxicity or disease progression. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Anti-tumor activity of BEZ235 was assessed by CT and PET. Early efficacy data are based on central review. Results: A total of 59 pts have entered the trial (13 breast , 10 CRC ). There were no DLTs with BEZ235 treatment. Frequently reported AEs included nausea, vomiting, diarrhea, fatigue/asthenia, anemia, and anorexia; they were mild or moderate, manageable, and reversible upon treatment discontinuation. AUC and Cmax increased non-proportionally with dose and were variable within and among pts. BEZ235 exhibited dose- and day-dependent PI3K inhibition as measured by elevation of plasma C-peptide levels. 2 PR (1 Cowden syndrome pt, 1 breast pt) and 16 MR were observed. 14 of 51 evaluable pts had stable disease ≥4 months; tumors from 6 of these 14 pts carried dysregulations of the PI3K pathway. 4 of the 14 (29%) patients with SD ≥4 months had breast cancer. 18 of 35 evaluable pts had detectable decreases of 18FDG- uptake. Conclusions: BEZ235 was well tolerated with a favorable safety profile. Available PD and efficacy data show that BEZ235 is active in pts (especially in those with PI3K pathway dysregulated tumors). Based on PK data, future studies will use a new formulation of BEZ235 with improved bioavailability and PK properties.
A dose-escalation study with the novel formulation of the oral pan-class I PI3K inhibitor BEZ235, solid dispersion system (SDS) sachet, in patients with advanced solid tumors.
Background: BEZ235 is a potent and highly specific oral dual mTOR/PI3K inhibitor. BEZ235 hard-gelatin capsule (Burris, ASCO 2010) and SDS capsule (Rodon, SABCS 2010) were reported previously. Here we present the dose escalation with the new BEZ235 formulation (BEZ235 SDS sachet). Methods: Phase I dose-escalation study of BEZ235 given orally once daily to adult patients with advanced solid tumors. A Bayesian logistic regression model with overdose control was used to guide dose escalation. Results: At the time of abstract submission, 25 patients have been treated with BEZ235 SDS sachet once daily at 4 dose levels: 800 mg (6); 1,000 mg (4), 1,400 mg (8), 1,600 mg (7). Tumor types enrolled included: colorectal (8), breast (4), NSCLC (3), renal (3) and sarcoma (3). 4/25 patients have been treated for >3 cycles, 10/25 patients progressed within the first three cycles of treatment and 8/25 are on treatment at time of abstract preparation. Maximum tolerated dose (MTD) for BEZ235 SDS sachet is 1,600 mg/d. Dose limiting toxicities (DLT) included: 2 cases of grade 3 fatigue/asthenia (at 1,400 mg) and 1 grade 3 thrombocytopenia (at 1,600 mg). Most common adverse events (AE) which are considered possibly treatment related included: nausea, diarrhea, vomiting and fatigue (G1-G3). At 1,600 mg, PK was evaluated in 7 patients. The absorption was slow with a tmax within 4 to 6 hours post-dose. The elimination half-life is ranging from 3.5 to 13.5 hours. At steady state, the median Cmax was 1,800 ng/mL (CV% = 38) and exposure was 22,375.5 ng.h/mL (CV% = 44). The accumulation ratio based on exposures between day 1 and steady state was estimated to be approximately 6 fold. Conclusions: BEZ235 SDS sachet was well tolerated with a favorable safety profile. Following the Bayesian model recommendation, the MTD for BEZ235 SDS sachet was determined as 1600 mg/d. Based on safety and pharmacology, this formulation is the chosen one for phase II clinical trials and it is being investigated in monotherapy in solid tumor patients with PI3K pathway alterations and in combination with trastuzumab for breast cancer.