The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias

Background

Idiopathic interstitial pneumonias (IIPs) are one of the most common complications in patients with lung cancer. In lung cancer patients with IIP, the most serious toxicity is acute exacerbation of IIP caused by anticancer treatment in Japan. However, there has been no consensus and no evidence presented, regarding optimal treatment for advanced lung cancer with IIP.

Patients and methods

Chemotherapy-naïve patients of inoperable stage, or post-operative recurrent non-small cell lung cancer (NSCLC) with IIPs were enrolled. Patients received paclitaxel at a dose of 100 mg/m² on Days 1, 8, 15, and carboplatin every 28 days at a target dose of area under the curve (AUC) 5.0 on Day 1.

Results

Between May 2004 and October 2008, 18 patients, including 6 with idiopathic pulmonary fibrosis (IPF), were enrolled and treated for a median of four cycles (range, 1-6). One patient (5.6%; 95% confidence interval (CI), 0-17%) with histologically confirmed IPF had acute exacerbation of IIPs associated with the treatment. The overall response rate was 61% (95% CI, 36-86%). The median progression-free survival, median survival time, and 1-year survival rate were 5.3 months, 10.6 months, and 22%, respectively.

Conclusion

This is the first report indicating that advanced NSCLC patients with IIP may benefit from chemotherapy. Weekly paclitaxel and carboplatin combination chemotherapy was as effective as conventional regimens in advanced NSCLC patients without IIP and was safer than previously reported for NSCLC patients with IIP. The results from this study would support, on ethical grounds, the conduct of a large-scale study to confirm the feasibility of this regimen.     

Imaging of Fibrogenesis in Patients with Idiopathic Pulmonary Fibrosis with cis-4-[18F]-Fluoro-l-Proline PET

Purpose  Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease for which no single diagnostic modality is able to evaluate the activity of the disease process. Cis-4-¹⁸F-fluoro-l-proline (¹⁸F-proline) was shown in animal studies to be a reliable marker for fibrosis formation. We tested this candidate radioligand for imaging of fibrogenesis in patients with IPF. Methods  Five patients with IPF proven by lung biopsy and computed tomography were included. Furthermore, we also included one patient with non-specific interstitial pneumonia (NSIP) and scleroderma and one with NSIP and organising pneumonia. Positron emission tomography (PET) acquisition was performed 1, 2 and 3h after injection of 400MBq ¹⁸F-proline. We scored ¹⁸F-proline activity visually and quantitatively by calculating the activity in the regions of interest over lung, liver and mediastinum. Results  We found low uptake of ¹⁸F-proline in the lungs of all patients with IPF. The highest uptake was seen at 2h post-injection, with a decline at 3h past injection. The differences in lung uptake between patients were small, except for one patient with NSIP and organising pneumonia who had a slightly higher ¹⁸F-proline uptake. No significant correlations between ¹⁸F-proline uptake and clinical parameters were found. Conclusions  Due to the low pulmonary uptake of ¹⁸F-proline in patients with IPF, ¹⁸F-proline does not seem to be a suitable radioligand to evaluate the activity of fibrosis formation in patients with IPF. The low uptake in the lungs of patients with interstitial fibrosis may be explained by the slow nature of fibrogenesis or to the relatively low dose of proline that can be used.     

活血化瘀法治疗特发性肺纤维化的研究与思考

特发性肺纤维化(Idiopathic Pulmonary Fibrosis,IPF)属于呼吸系统难治性疾病之一,西医治法疗效欠佳且有一定不良反应.IPF归属于中医"肺痹""肺痿"等范畴,在其发展过程中,"瘀血"贯穿始终.中医药治疗IPF具有一定疗效,活血化瘀法是中医特色治法之一,在IPF的治疗中占有重要地位.通过系统文...     

大黄䗪丸对TGF-β1干预后A549细胞增殖的影响

目的基于特发性肺纤维化(IPF)患者存在肺络干血假说,观察大黄?虫丸含药血清对TGF-β1干预后A549细胞增殖的影响,探讨其防治特发性肺纤维化的作用机制。方法正常培养并取对数生长期A549细胞,5 ng/mL的TGF-β1对其干预后,Masson染色观察上皮-间充质转化(EMT)过程;选择吡非尼酮作为阳性对照药,采用血清药理学和cck-8法观察不同浓度大黄?虫丸含药血清对TGF-β1干预后A549细胞增殖的影响。结果成功获取发生EMT的A549细胞;24 h,OD值从高到低依次为:空白对照组(K组)、大黄?虫丸含药血清中剂量组(Z组)、大黄?虫丸含药血清小剂量组(X组)、模型组(M组)、大黄?虫丸含药血清大剂量组(D组)、西药组(P组);48 h,OD值从高到低依次为:K组、M组、Z组、X组、P组、D组;72 h,OD值从高到低依次为:K组、M组、D组、Z组、P组、X组。结论大黄?虫丸含药血清对TGF-β1干预后A549细胞增殖率有影响,推测大黄?虫丸对IPF的保护机制可能与不同程度阻断或逆转了TGF-β1诱导的EMT有关。