我父亲肺鳞癌的治疗贴(2014年3月1日驾鹤西去）

A phase I dose finding study of the 3-day administration of BIBW 2992, an irreversible dual EGFR/HER-2 inhibitor, in combination with three-weekly docetaxel in patients with advanced solid tumors.
Background: BIBW 2992 (Tovok) is a potent, irreversible, new generation TKI, an inhibitor of EGFR and HER-2 (IC50 0.5 and 14 nM, respectively). A Phase I dose finding study of BIBW 2992 with docetaxel is reported. Methods: Patients (pts) had advanced solid malignancies and received docetaxel 75 mg/m2 i.v. on Day 1 and oral BIBW 2992 once daily on Days 2-4, in 3-week cycles. The BIBW 2992 dose was doubled in successive cohorts of 3-6 pts until ≥Grade 2 CTC, after which dose escalation occurred in increments of ≤50%. The MTD cohort expanded to 12 pts. PK profiles were taken on Days 1 and 2 of treatment cycles 1 and 2. Results: 40 evaluable pts (17 male) were treated at the following doses of BIBW 2992: 10 mg (6), 20mg (3), 40 mg (6), 60 mg (4), 90 mg (13), 120 mg (5) and 160 mg (3). Common adverse events (AEs) (% of patients) were fatigue (62.5%), diarrhea (57.5%), anorexia and stomatitis (52.5%), alopecia (50%), rash (42.5%), nausea and pyrexia (40%), vomiting (35%), general physical health deterioration (32.5%), and peripheral sensory neuropathy (30%). Two DLTs occurred: one pt had Grade 4 neutropenia (a DLT if complicated or lasting >5 or 7 days) and one had Grade 3 nausea, vomiting and diarrhea (BIBW 2992 120 mg). Both fully recovered upon treatment interruption/dose reduction (docetaxel 60 mg/m2/BIBW 2992 90 mg). The MTD was 90 mg BIBW 2992 with docetaxel 75 mg/m2. Four pts (breast cancer [2], thymoma [1], oesophageal carcinoma [1]) had a PR. One breast cancer pt had a confirmed CR. Two of these pts had prior taxane treatment. Ten pts had SD and received treatment for ≥6 courses with 4 receiving treatment for ≥9 courses. There was no deviation from dose-linearity of BIBW 2992 and docetaxel. Docetaxel (75 mg/m2) plasma concentration-time profiles, Cmax and AUC0-∞ before and after BIBW 2992 dosing were comparable. Conclusions: BIBW 2992 90mg administered for 3 days after docetaxel 75 mg/m2 is well tolerated and is the recommended dose for further trials. Objective responses or durable SD (≥6 months) were seen in 15 (39%) pts. No PK interaction was observed between BIBW 2992 and docetaxel.

老马，我母亲服特半个月以后眼部周围出现了皮疹，可以使用哪种方法进行处理哈 谢谢

* k+ ]9 Q0 x# ^, a5 `  |0 f昨天出院了。大前天发烧到39.3度，可能是输血的反应。
老爸说胃口差，停了2992了，打算停几天再说。
1 G# c: l% }  t昨天爬到5楼，心率也没超100，感觉不错。
这次DC-CIK一共用了69800元，一次人工，一次机器。
) K( u6 E* \2 [6 E  w5 L一共查了三次淋巴细胞亚组数据，下周一贴上来。

老马 发表于 2012-9-15 23:54

                               
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* W$ o8 t! {# B- \/ X昨天出院了。大前天发烧到39.3度，可能是输血的反应。
: j- f8 g. c% O8 S老爸说胃口差，停了2992了，打算停几天再说。
昨天 ...

* W( G" R$ T" I/ A1 z这个费用就是整个回合的？自己需要花费多少？
/ K$ |# i( s+ x- Y6 ?$ k' w

老马，我家特吃了两个月了， 2992 装了7天60mg的备着，过阵子可能用上。 你家情况这么好，也不知道我家脑转的能不能控制住，没底……

这回生物治疗一共用了69800元，自己出13614元，报了80.5%。
生物治疗对我家是有效果的，这几天精神非常好，淋巴亚组细胞数据也有提高。
打算国庆后再去做二次。生物治疗适合于肿瘤负荷小，稳定期的病人，进展期几乎无效。
4 u7 j  |# V. m

今天开始重新吃BIBW 2992，打算吃一周。

BIBW 2992 Plus Simvastatin
Detailed Description:
& \5 S  {  i: z8 ~  ^" YOne of the main reasons of resistance to EGFR tyrosine kinase inhibitors (TKIs) is that there are alternative mechanisms for persistent activating EGFR downstream signaling, including both RAS/Erk and PI3K/Akt kinase pathways. Therefore, simultaneous inhibition of both pathways would be necessary to reduce tumor cell survival more effectively. One of the candidate combinations is concurrent use of EGFR-TKIs and statins, which are irreversible inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and have been used to treat hypercholesterolemia through blocking the mevalonate biosynthesis pathway. Beside the cholesterol lowering effect, statins have been shown to induce apoptosis in several tumor types. It affects the synthesis of other products of the mevalonate pathway such as isoprenoids, which are used as substrates for prenylation. Attachment of isoprenoids to RAS proteins facilitates their anchoring to the cell membrane where they carried out their roles. By interrupting the biosynthesis of mevalonate, statins inhibit activation of RAS and downstream signaling cascades, including the RAF/MEK/ERK and PI3K/AKT, which play critical roles in regulation of cell survival and proliferation. Therefore, it seems to be a promising therapeutic approach overcoming tumor resistance to EGFR-TKIs, which is associated with RAS activation.

) ]6 {$ [1 u+ aAccording to the recent clinical result of phase II trial, a randomized phase II study of gefitinib with or without simvastatin in previously treated patients with advanced NSCLC conducted by Han et al.37 gefitinib plus simvastatin combination produced higher response rates than gefitinib alone in patients with non-adenocarcinoma (5/13 [39%] v 1/13 [8%], P=0.06). This finding suggests that simvastatin may enhance sensitivity to gefitinib in non-adenocarcinoma that is relatively resistant to gefitinib. Moreover, by Mantha et al.35 demonstrated that the combination of gefitinib and lovastatin showed significant synergic cytotoxic effects in vitro in a total of 16 squamous cell carcinomas, NSCLC, and colon carcinoma cell lines. Of special interest, these cell lines did not possess the activating mutations of EGFR, which confer increased sensitivity to gefitinib. Nevertheless, combining lovastatin with gefitinib induced more significant inhibition of AKT activation than either agent alone. Additionally, lovastatin significantly enhanced the sensitivity to gefitinib treatment regardless PTEN loss in glioblastoma cell lines. These results suggest that statins can augment EGFR inhibition.
6 [8 ]+ Y' r) Y. `) ]7 B3 z

我妈今天去挂了吴医生的号，问了一些问题，
0 P) \8 I, N! O8 v, S( Y7 }: d1.人工抽血与机器抽血相比，机器抽血效果更好。
0 l: C" u" \3 T* t: G9 ^2.回输血后有发热反应的效果更好。
% ^8 F# B& i5 c) H9 R3.病人本身的免疫力不能太差。
, T5 a1 a+ I% W! v8 J6 O  N8 `4.浙江省人民医院用的是DC-CIK，分开培养，混合回输。
+ [: H/ v; \% S! O! u5.DC-CIK只提高了一部分T免疫细胞，对B细胞无效。
) Q# U1 X' ?, ]* K! N' t6.一个疗程的DC-CIK治疗，有效持续时间是1多个月。

老马 发表于 2012-9-27 20:18

# Z+ |, K* u3 l' Z4 N! B* }+ U                               
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) d8 `, ]* U. u$ J5 ]我妈今天去挂了吴医生的号，问了一些问题，
0 s! P2 ~9 h  B( a: W2 p1.人工抽血与机器抽血相比，机器抽血效果更好。
2.回输血后有 ...

3.病人本身的免疫力不能太差。------也就是说如果病人体质很弱了，做了就没有效果？
! {; c8 Y  W: o* \5.DC-CIK只提高了一部分T免疫细胞，对B细胞无效。-----B细胞是什么啊？
, N! B% A& Q! P8 `" H; `6.一个疗程的DC-CIK治疗，有效持续时间是1多个月。------也就是说最好3个月要做2个疗程，对么？