Department of Surgery, Kansai Medical University, Hirakata, Osaka 570-8507, Japan.
Anticancer Res. 2011 Oct;31(10):3567-71.
We reported that doxorubicin and cyclophosphamide (DC) followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. However, as one of the side effects of paclitaxel, neuropathy was noted in up to 30% of patients. Cyclooxygenase-2 (COX-2) and its derived prostaglandins play a role in stimulating angiogenesis, inhibiting apoptosis, and suppressing the immune response. Some recent studies showed that COX-2 inhibitors, such as meloxicam, have the potential to enhance tumor suppression and reduce the severity of paclitaxel-induced neuropathy.
Four cycles of DC (doxorubicin: 60 mg/m(2) and cyclophosphamide: 600 mg/m(2)) administered intravenously (i.v.) on day 1 every 21 days were followed by 12 cycles of paclitaxel i.v. (80 mg/m(2)) every 7 days, prior to surgery. During paclitaxel therapy, breast cancer patients were administered meloxicam (10 mg per day) daily, when experiencing symptoms of grade 2 neuropathy (motor or sensory). The primary endpoint was the pCR rate achieved with the treatment.
Forty-three patients received preoperative chemotherapy between April 2004 and March 2007 at six centers. The patient population was identified from a database of the Japan Breast Cancer Research Network. Clinical responses were rated as clinically complete response (cCR) in 9 patients (22%), clinically partial response (cPR) in 25 patients (59%), and clinically stable disease (cSD) in 9 patients (19%). pCR was seen in 25.6%. In addition, we identified 15 patients, who developed grade 2 neuropathy during paclitaxel therapy and subsequently received meloxicam. Meloxicam application had a marked effect within 28 days of initiation. The sensory neuropathy of the patients was reduced gradually, but their motor neuropathy did not improve. Five out of the 15 patients with neuropathy experienced symptom improvement after meloxicam treatment (p<0.05; before versus after 2 months of meloxicam administration). Furthermore, among the 15 patients, who received meloxicam, clinical responses were rated as cCR in 2 patients, cPR in 4 patients, and cSD in 9 patients. The pCR was seen in 4 patients (26.7%).
Although meloxicam in combination with DC and weekly paclitaxel chemotherapy did not show promising therapeutic activity, it may provide some relief for neuropathy.
我们曾报道多柔比星和环磷酰胺（DC）序贯每周紫杉醇是一种用于乳腺癌患者的有效且可管理的术前方案。然而，作为紫杉醇的一种副作用，多达 30%的患者会出现周围神经病变。环氧化酶-2（COX-2）及其衍生的前列腺素在刺激血管生成、抑制细胞凋亡和抑制免疫反应方面发挥作用。一些最近的研究表明，COX-2 抑制剂，如美洛昔康，有可能增强肿瘤抑制作用并减轻紫杉醇引起的周围神经病变的严重程度。
每 21 天静脉注射（iv）一次多柔比星（60mg/m²）和环磷酰胺（600mg/m²），共 4 个周期，随后在手术前进行 12 个周期的紫杉醇 iv（80mg/m²），每周一次。在紫杉醇治疗期间，当乳腺癌患者出现 2 级神经病变（运动或感觉）症状时，每天给予美洛昔康（10mg/天）。主要终点是治疗后获得的 pCR 率。
2004 年 4 月至 2007 年 3 月期间，六家中心的 43 名患者接受了术前化疗。患者人群是从日本乳腺癌研究网络的数据库中确定的。临床反应评为临床完全缓解（cCR）的有 9 例（22%），临床部分缓解（cPR）的有 25 例（59%），临床稳定疾病（cSD）的有 9 例（19%）。pCR 为 25.6%。此外，我们发现 15 例患者在紫杉醇治疗期间出现 2 级神经病变，随后接受了美洛昔康治疗。美洛昔康在开始治疗后 28 天内有明显效果。患者的感觉神经病变逐渐减轻，但运动神经病变没有改善。15 例神经病变患者中有 5 例在美洛昔康治疗后症状改善（p<0.05；治疗前与治疗后 2 个月）。此外，在接受美洛昔康治疗的 15 例患者中，临床反应评为 cCR 的有 2 例，cPR 的有 4 例，cSD 的有 9 例。pCR 为 4 例（26.7%）。
虽然美洛昔康联合 DC 和每周紫杉醇化疗并未显示出有前景的治疗活性，但它可能为神经病变提供一些缓解。
