Yale University School of Medicine, Section of Medical Oncology, 333 Cedar Street; FMP 116, New Haven, CT 06520, USA.
Anticancer Res. 2010 Jul;30(7):2905-9.
No therapeutic standard of care exists for patients who have progressed following first-line treatment with a gemcitabine-based regimen with advanced pancreatic cancer. Approximately half of the patients failing upfront treatment present with ECOG PS 1-2 and are willing to undergo further treatment. Docetaxel activity against pancreatic cancer is reported both in the preclinical and clinical setting. This study retrospectively evaluated the role of docetaxel as second-line therapy in patients with gemcitabine-refractory disease.
Between January 2006 and November 2009, 17 patients (median age of 61 years) with advanced pancreatic adenocarcinoma, after receiving gemcitabine-containing chemotherapy as first-line median ECOG performance status 1 and with adequate organ function, were treated with either weekly docetaxel at 25 mg/m(2) or 3-weekly docetaxel regimen (docetaxel at 75 mg/m(2) or docetaxel-gemcitabine-capecitabine or docetaxel-gemcitabine) until progressive disease. Serum CA19-9 levels were measured every 3/4 weeks and CT scans performed after every eight/nine weeks.
Docetaxel dose intensity was 90% in the patients who received weekly docetaxel, 85% in docetaxel-erlotinib regimen and 65% in 3-weekly regimen (docetaxel-gemcitabine-capecitabine, docetaxel-gemcitabine). Only one objective response (6%) to treatment was obtained (docetaxel-gemcitabine), while 5 patients achieved stable disease (weekly docetaxel). Median progression-free survival was 8 weeks (range: 3-16 weeks) and median survival was 4.0 months (range: 2.0-6.5 months). No toxicity with grade >3 associated with docetaxel was observed.
Docetaxel seems to have mild activity in the treatment of gemcitabine-resistant metastatic pancreatic cancer. Although some patients may benefit from the treatment, other dosing regimens and novel taxanes such as Nab-paclitaxel should be explored in this setting.
对于接受吉西他滨为基础的方案一线治疗后进展的晚期胰腺癌患者，目前尚无治疗标准。大约一半的初始治疗失败的患者 ECOG PS 评分为 1-2，愿意接受进一步治疗。多西紫杉醇在临床前和临床环境中均对胰腺癌具有活性。本研究回顾性评估了多西紫杉醇作为吉西他滨耐药疾病二线治疗的作用。
2006 年 1 月至 2009 年 11 月，17 名（中位年龄 61 岁）接受过含吉西他滨化疗的一线治疗后进展的晚期胰腺腺癌患者，中位 ECOG 体力状况为 1，且器官功能良好，接受每周一次多西紫杉醇 25mg/m2或每 3 周一次的多西紫杉醇方案（多西紫杉醇 75mg/m2或多西紫杉醇-吉西他滨-卡培他滨或多西紫杉醇-吉西他滨）治疗，直至疾病进展。每 3/4 周测量血清 CA19-9 水平，每 8/9 周进行 CT 扫描。
每周接受多西紫杉醇治疗的患者多西紫杉醇剂量强度为 90%，接受多西紫杉醇-厄洛替尼方案治疗的患者为 85%，接受 3 周方案（多西紫杉醇-吉西他滨-卡培他滨、多西紫杉醇-吉西他滨）治疗的患者为 65%。仅 1 例患者（6%）获得客观缓解（多西紫杉醇-吉西他滨），5 例患者（每周多西紫杉醇）获得稳定疾病。中位无进展生存期为 8 周（范围：3-16 周），中位总生存期为 4.0 个月（范围：2.0-6.5 个月）。未观察到与多西紫杉醇相关的 3 级以上毒性。
多西紫杉醇似乎对吉西他滨耐药转移性胰腺癌具有一定的活性。尽管一些患者可能受益于治疗，但在这种情况下，应探索其他剂量方案和新型紫杉醇，如 Nab-紫杉醇。
