Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer - Potential benefits and COX-2 as the common mediator in pain, toxicities and survival?
Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer - Potential benefits and COX-2 as the common mediator in pain, toxicities and survival?
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DOI：
10.1097/01.coc.0000217818.07962.67
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发表时间：
2006-06-01
影响因子：
2.6
通讯作者：
Janjan, Nora
中科院分区：
文献类型：
--
作者：
Lin, Edward H.;Curley, Steven A.;Janjan, Nora
目的：COX-2激活可能介导卡培他滨诱导的毒性，如手足综合征（HFS）和结直肠癌进展，同时使用塞来昔布可改善这两种情况。患者和方法：从2000年10月到2003年12月，66例转移性结直肠癌患者同时接受卡培他滨1000mg /m(2)/d b.d和塞来昔布200mg b.d （XCEL）治疗。24例首次化疗，42例二线治疗；34例XCEL合并放疗。结果：XCEL的中位持续时间为7.2个月（1.5-38个月）。90%的2/3级HFS（17%）发生在6个月后，3/4级腹泻的发生率为8%。总缓解率为38%(95%可信区间[CI]， 26-51%)， 11例患者（17%）达到完全缓解，2例患者（3%）接近完全缓解。6例（9%）患者在维持治疗反应后可以手术切除。中位无进展生存期（PFS）和总生存期（OS）分别为8.3个月（95% CI, 7.0-11.0个月）和22个月（95% Cl, 17.8-31.5个月）。乳酸脱氢酶（LDH）水平正常的患者（n = 37）比LDH水平高的患者（n = 29）的中位PFS改善14.5个月（P = 0.0001）， OS改善31.5个月（P = 0.005）。结论：XCEL整合放疗可提高反应率和生存率，降低毒性，特别是转移性结直肠癌患者的HFS，因此开展了一项随机III期研究。
Objective: COX-2 activation may mediate capecitabine induced toxicities, eg, hand-foot syndrome (HFS) and colorectal cancer progression, both of which may be improved by concurrent celecoxib.Patients and Methods: From October 2000 to December 2003, 66 patients with metastatic colorectal cancer received concurrent capecitabine at 1000 mg/m(2)/d b.i.d. and celecoxib at 200 mg b.i.d. (XCEL). Twenty-four patients were chemo-naive, 42 patients were second-line; while 34 had XCEL with radiation.Results: The median duration of XCEL was 7.2 months (range, 1.5-38 months). Ninety percent of Grade 2/3 HFS (17%) occurred after 6 months and incidence of grade 3/4 diarrheas was 8%. The overall response rate was 38% (95% confidence interval [CI], 26-51%), with 11 patients (17%) achieving complete responses and 2 patients (3%) with near complete responses. Six patients (9%) become resectable after sustaining treatment response. The median progression-free survival (PFS) and overall survival (OS) was 8.3 months (95% CI, 7.0-11.0 months) and 22 months (95% Cl, 17.8-31.5 months), respectively. Improved median PFS of 14.5 months (P = 0.0001) and OS of 31.5 months (P = 0.005) were noted in patients with normal lactate dehydrogenase (LDH) levels (n = 37) than patients with high levels of LDH (n = 29).Conclusions: XCEL integrating radiation may improve response rate and survival and reduce toxicities, notably HFS for patients with metastatic colorectal cancer, leading to a randomized phase III study.