Tobinick Edward Lewis
Institute for Neurological Research, Los Angeles, California 90095, USA.
Clin Ther. 2003 Aug;25(8):2279-88. doi: 10.1016/s0149-2918(03)80219-9.
Parallel bodies of research suggest both a central role for osteoclasts in tumor-induced destruction of bone and the ability of biologic tumor necrosis factor-alpha (TNF-alpha) antagonists to attenuate the osteoclast-mediated bone destruction that accompanies a variety of nonmalignant disorders. Additional studies have implicated TNF-alpha in the promotion of osteoclast-mediated malignant osteolysis and the pathogenesis of neuropathic pain. TNF-alpha antagonists have the potential to interfere in both processes.
This article reviews the cases of 2 patients with treatment-refractory pain due to cancer metastases to bone who were given targeted injections of the biologic anti-TNF agent etanercept based on its potential to interfere directly with both malignant activation of osteoclasts and neuropathic pain.
One patient had a diagnosis of non-small cell lung cancer and the other had a diagnosis of breast cancer. Both presented with treatment-refractory pain due to bone metastases. The 2 patients received etanercept 25 mg by targeted SC injection in anatomic proximity to the site of spinal metastasis for relief of their treatment-refractory pain.
Both patients experienced rapid, substantial, and sustained relief of chronic refractory pain at the treatment site after targeted administration of etanercept. Symptomatic improvement was correlated with objective measures of improvement, including weight gain in 1 patient and decreased uptake of radioactive tracer at the targeted site on positron emission tomography in the other.
Etanercept delivered by targeted SC injection may be of clinical benefit in selected patients with treatment-refractory pain caused by bone metastases. Clinical trials are needed to define the potential benefit of biologic TNF-alpha antagonists in the treatment and prevention of malignant osteolysis.
一系列相关研究表明，破骨细胞在肿瘤诱导的骨破坏中起核心作用，生物性肿瘤坏死因子-α（TNF-α）拮抗剂能够减轻伴随多种非恶性疾病出现的破骨细胞介导的骨破坏。另外的研究表明，TNF-α在促进破骨细胞介导的恶性骨溶解及神经性疼痛的发病机制中发挥作用。TNF-α拮抗剂有可能对这两个过程都产生干预作用。
本文报告了2例骨转移癌导致难治性疼痛的患者，基于生物抗TNF药物依那西普有可能直接干预破骨细胞的恶性激活及神经性疼痛，对其进行了靶向注射治疗。
1例患者诊断为非小细胞肺癌，另1例为乳腺癌。二者均因骨转移出现难治性疼痛。这2例患者在脊柱转移部位附近接受了25 mg依那西普的靶向皮下注射，以缓解难治性疼痛。
靶向注射依那西普后，2例患者治疗部位的慢性难治性疼痛均迅速、显著且持续缓解。症状改善与客观改善指标相关，其中1例患者体重增加，另1例患者正电子发射断层扫描显示靶向部位放射性示踪剂摄取减少。
对于某些因骨转移导致难治性疼痛的患者，靶向皮下注射依那西普可能具有临床益处。需要开展临床试验来明确生物性TNF-α拮抗剂在治疗和预防恶性骨溶解方面的潜在益处。
