我父亲肺鳞癌的治疗贴(2014年3月1日驾鹤西去）

老马 · 发表于 2012-8-29 10:54:12

咳血止住了2天，吃2992 3天了，又开始有轻微咳血，怀疑与2992有关，又停了。
今天用机器采血，再回输上次人工采的血。

老马 · 发表于 2012-9-3 19:53:19

大前天出院了，出院前住进一位病友，夫妻俩重感冒，咳嗽了一整晚，结果把我父母也传染上了.
二位老人流鼻涕，咳嗽，这二天，每天挂3g VC，好多了。

英雄武松 · 发表于 2012-9-4 01:02:20

到底，此次的2992如何呢。
祝福。

小辣椒 · 发表于 2012-9-5 13:14:56

这么多年了，你父亲在你们的照顾下已经相当不错了。愿2992有效。关注中。

dashan666 · 发表于 2012-9-8 09:41:45

学习了小马哥的治疗贴子，收获颇多，加油。

老马 · 发表于 2012-9-9 15:15:42

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 · 发表于 2012-9-9 15:44:44

Neratinib Has Limited Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer
GENEVA -- October 23, 2008 -- Neratinib (HKI-272) is well tolerated and shows limited efficacy in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with erlotinib/gefitinib treatment, according to results of a 3-arm, phase 2 study.

Erlotinib and gefitinib can provide dramatic responses in patients with NSCLC, although virtually all of these patients eventually develop progressive disease. Earlier research demonstrated that patients with advanced NSCLC who received prior gefitinib or erlotinib treatment had stable disease after treatment with neratinib.

The T790M epidermal growth factor receptor (EGFR) gene mutation can confer resistance to erlotinib and gefitinib. Neratinib is an EGFR inhibitor and is active against the T790M mutation. Therefore, researchers tested this compound in patients who received at least 12 weeks of erlotinib or gefitinib.

The results of this study were presented here at the 20th International Symposium of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR).

Investigator Benjamin Besse, MD, PhD, Department of Medicine, Gustave Roussy Institute, Villejuif, France, discussed results in a poster session on October 22.

The primary endpoint was objective response rate (ORR), defined as complete plus partial responses. Secondary endpoints included safety, clinical benefit rate, duration of response, and progression-free survival.

A total of 167 patients (median age, 60 years; male, 29%) were divided into 3 groups: arm A, progression after >=12 weeks of erlotinib or gefitinib treatment and tumour positive for EGFR mutation (n = 91); arm B, progression after >=12 weeks of erlotinib or gefitinib treatment and tumour negative for EGFR mutation (n = 48); and arm C, no prior EGFR tyrosine kinase inhibitor treatment, adenocarcinoma, <=20 pack-year smoker and current nonsmoker, and tumour positive or negative for EGFR mutation (n = 28).

Neratinib was administered orally initially at 320 mg daily, later reduced to 240 mg by protocol amendment after gastrointestinal adverse effects were reported. Efficacy evaluation was done according to the Response Evaluation Criteria in Solid Tumours (RECIST) classification.

Results show no significant differences in ORR across the treatment arms: arm A, 2%; arm B, 2%; and arm C, 4%. The same was seen for patients with stable disease (47%, 46%, and 39%, respectively); for progression-free survival (11.6, 14.7, and 7.4 weeks, respectively); and for clinical benefit rates at 16 weeks (24%, 19%, and 36%, respectively).

Although neratinib did provide apparent limited efficacy in these patients with NSCLC, Dr. Besse indicated that the molecular characteristics and prior erlotinib/gefitinib treatment variables did not correlate with neratinib efficacy.

Dr. Besse explained, "We were expecting more activity in the erlotinib/gefitinib arm than we saw ... and one of the explanations for this is probably based on the tumour profile, as [from the biopsy to the analysis] the patients received platinum-based therapy for at least 12 weeks."

老马 · 发表于 2012-9-9 15:47:27

Neratinib是泛ErbB（EGFR、ErbB2和ErbB3）不可逆TKI。基于Ⅰ期研究结果，目前正在开展临床研究，探讨在吉非替尼或厄洛替尼治疗后进展的NSCLC患者中，neratinib（240 mg/d）是否能克服T790M突变或MET扩增导致的TKI耐药。但一些临床前研究显示了不利结果，一种EGFR 19外显子缺失的细胞株PC-9在暴露于neratinib时，产生了T790M突变；在鼠L858R-T790M肿瘤模型中，单用neratinib未使肿瘤缓解。故neratinib对T790M突变者是否有效尚不得知。　