卡培他滨沙利度胺治疗晚期乳腺癌对比研究

目的观察沙利度胺联合卡培他滨对晚期乳腺癌的疗效及毒性。方法46例Ⅲ～Ⅳ晚期乳腺癌随机分为卡培他滨联合沙利度胺组（A组）和卡培他滨组（B组）,A组23例接受卡培他滨2500mg/m2,分早晚两次餐后30min温开水送服,第1～14天,间隔7天,沙利度胺100mg,口服,第1～14天,21天为1周期,化疗4个周期;B组23例不服用沙利度胺。结果A组：CR3例,PR9例,SD8例,PD3例,有效率52.2%,疾病控制率为87%;B组：CR1例,PR4例,SD13例,PD5例,有效率21.7%,疾病控制率为73.9%。结论卡培他滨联合沙利度胺治疗晚期乳腺癌疗效较好,不良反应轻,患者可耐受。     

Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in mouse cancer cachexia models

Purpose

To clarify the potential of parathyroid hormone-related protein (PTHrP) and interleukin-6 (IL-6) as cachectic factors in a colon 26 model and the effects of capecitabine on cancer cachexia as determined by plasma levels of IL-6 and PTHrP and body weight loss.

Methods

From two colon 26 sublines-cancer cachectic clone20 and non-cachectic clone5 plasma levels of PTHrP protein and mRNA expression levels in tumor tissues were compared. An IL-6 neutralizing antibody, a PTHrP neutralizing antibody, and capecitabine were administered into mice bearing clone20 and their anticachectic effects evaluated.

Results

The plasma level of PTHrP protein in mice bearing clone20 was higher than that in mice bearing clone5. The expression level of PTHrP mRNA was 49-fold higher in tumor tissues of clone20 than of clone5, according to GeneChip^® analysis. PTHrP antibody as well as IL-6 antibody suppressed wasting of the body and gastrocnemius and adipose tissue weights. PTHrP antibody suppressed the induction of hypercalcemia but not hypoglycemia or elevation of IL-6, whereas IL-6 antibody suppressed the induction of hypoglycemia but not hypercalcemia or elevation of PTHrP. Capecitabine, a fluorinated pyrimidine anticancer agent, improved body wasting of mice bearing clone20 at a low dose with no reduction of tumor volume. Furthermore, capecitabine lowered the levels of PTHrP and IL-6 in plasma and suppressed hypoglycemia and hypercalcemia in this model. Capecitabine also showed anticachectic effects on cachexia in a cancer model induced by human cervical cancer cell line Y (also known as Yumoto).

Conclusions

PTHrP and IL-6 were found to be factors in the development of cachexia in a colon 26 cancer model, and capecitabine improved cancer cachexia by suppressing the plasma levels of IL-6 and PTHrP in colon 26 and Y cachectic models.     

Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer

PURPOSE: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. METHODS: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. RESULTS: Radiologic examination showed that tumor volume decreased by 68.2% +/- 20.5% in the FL group and 68.3% +/- 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). CONCLUSION: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.     

基于FAERS数据库的氟尿嘧啶和卡培他滨不良事件信号挖掘研究

目的 挖掘氟尿嘧啶和卡培他滨的药物不良事件（ADE）信号,为安全用药提供参考。方法 提取FAERS数据库2017年第1季度至2021年第3季度共19个季度内上述药物的不良反应报告数据,采用报告比值比法（ROR）和综合标准法（MHRA）进行信号挖掘。结果 去重后共检出654个ADE信号,累及27个系统器官分类,其中氟尿嘧啶的ADE信号主要集中在血液及淋巴系统疾病、全身性疾病及给药部位各种反应、胃肠系统疾病和各类神经系统疾病等;卡培他滨的ADE信号主要集中在胃肠系统疾病、皮肤及皮下组织类疾病、全身性疾病及给药部位各种反应和血液及淋巴系统疾病等。在消化系统毒性方面,两种药物均显示出较强的相关性,区别在于氟尿嘧啶与血液系统毒性、心脏相关毒性关联性更强,而卡培他滨与皮肤相关毒性关联性更强。结论 检出的氟尿嘧啶和卡培他滨ADE信号中,大多数与药品说明书重合性较好,证明了本研究的可靠性。本研究还发现了药品说明书未记载的ADE,可供临床参考。     

Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I–II Multicenter Study of the Dutch Colorectal Cancer Group

Background We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer. Methods T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m² twice daily (days 1–14, 25–38) added to RT with 50.4 Gy and surgery after 6–8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point. Results Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m² was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21. Conclusion Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.     

Contemporary issues and the potential uses of capecitabine in metastatic breast cancer

Since its first regulatory approval more than 10 years ago, oncologists have gained wide experience in using the oral fluoropyrimidine, capecitabine, as monotherapy or in combination with other agents and the body of evidence supporting these approaches continues to grow. Alongside this increasing experience has been the appearance of new challenges in patient management. We now recognise several different biological subtypes of breast cancer, such as HER2-positive disease. The standard of care in these tumours comprises anti-HER2 therapy, and phase III data show that capecitabine can be effectively combined with such agents. Another increasingly prominent and currently unresolved issue resulting from more effective treatment of metastatic disease is the management of patients with brain metastases. The introduction of new, well-tolerated, oral chemotherapies also provides the opportunity for longer duration of therapy. These new clinical scenarios are discussed in the current review.     

替吉奥或卡培他滨联合奥沙利铂治疗晚期胃癌效果比较

目的：对比替吉奥联合奥沙利铂（L-OHP）与卡培他滨联合L-OHP治疗晚期胃癌的疗效和不良反应。方法对2011年3月至2014年12月郑州人民医院收治的93例晚期胃癌患者资料进行回顾性分析。其中替吉奥联合L-OHP治疗组（SL组）48例,卡培他滨联合L-OHP治疗组（XL组）45例。SL组：给予替吉奥每天80 mg／m2,分两次口服,第1天至第14天;L-OHP 130 mg／m2,静脉滴注2 h,第1天。XL组：卡培他滨每天2000 mg／m2,分两次口服,第1天至第14天;L-OHP 130 mg／m2,静脉滴注2 h,第1天。化疗周期为21 d。完成2个周期后评估疗效和不良反应。结果SL组和XL组总有效率分别为52.08%（25／48）和53.33%（24／45）,差异无统计学意义（P＞0.05）。SL组消化道不良反应发生率高于XL组[52.08%（25／48）和24.44%（11／45）,P＜0.05]。SL组口腔黏膜炎发生率低于XL组[25.00%（12／48）和51.11%（23／45）,P <0.05]。结论替吉奥联合L-OHP与卡培他滨联合L-OHP治疗晚期胃癌均安全、有效。     

希罗达联合吉西他滨或长春瑞滨治疗晚期三阴性乳腺癌的临床观察

目的观察以卡培他滨为主的联合化疗方案治疗对蒽环类或紫杉类耐药的晚期三阴性乳腺癌的疗效和不良反应。方法共有38例复发转移的三阴性乳腺癌患者入组,分别采用卡培他滨联合吉西他滨（GX方案）或长春瑞滨（NX方案）化疗。卡培他滨2.0g/（m^2/d）,早晚各1次,餐后30min口服,d1~14;长春瑞滨25mg/m^2,d1,8,静滴;吉西他滨1 000mg/m^2,d1,8,静滴;21天为1个周期。结果 38例患者共完成133个周期化疗,中位化疗周期为4个周期。本组总有效率（RR=CR＋PR）为18.4%,临床获益率（CR＋PR＋SD）为44.7%。中位无进展生存（PFS）为7.6个月,中位总生存（OS）为12.5个月。两组化疗方案疗效无统计学差异。无化疗相关死亡病例,主要不良反应为骨髓抑制及手足综合症。结论以卡培他滨为主的两药联合方案,对晚期TNBC患者疗效有限,提示含卡培他滨的联合化疗方案可用于晚期三阴性乳腺癌,但能否作为首选方案尚需大样本、多中心的临床研究。     

XELOX方案和mFOLFOX6方案治疗转移性结直肠癌的疗效与毒副反应观察

目的：观察XELOX（卡培他滨＋奥沙利铂）方案和mFOIFOX6（奥沙利铂＋5-Fu＋亚叶酸钙）方案治疗转移性结直肠癌的近期疗效及毒副反应。方法64例转移性结直肠癌患者随机分为XELOX组30例和mFOLFOX6组34例。 XELOX组给予奥沙利铂130 mg/m2,静脉滴注2 h,第1天;卡培他滨1000 mg/m2,分早晚2次口服,连用14 d;3周为1周期。 mFOLFOX6组给予奥沙利铂85 mg/m2,静脉滴注2 h,第1天;亚叶酸钙400 mg/m2,静脉滴注2 h后予5-氟尿嘧啶400 mg/m2,静脉推注,后续2400 mg/m2,持续静滴46 h,每2周重复,4周为l周期。患者均接受至少2周期的化疗。依据RESIST评价近期疗效,依据WHO标准评价毒副反应。结果XELOX组与mFOLFOX 6组有效率分别为43.3%和41.2%,两组中位疾病进展时间分别为5.5个月与6.0个月,差异无统计学意义（P〉0.05）;XELOX组恶心呕吐发生率显著低于mFOIFOX6组（P〈0.05）;XELOX组手足综合征发生率明显高于mFOLFOX 6组（P〈0.05）,但程度较轻,主要为Ⅰ-Ⅱ度。其他的毒副反应两组无明显差异（P〉0.05）。结论XELOX方案与mFOLFOX6方案治疗转移性结直肠癌疗效确切且相似,毒副反应可耐受,XELOX方案更安全。