人参固本口服液治疗放化疗骨髓抑制机制探讨

骨髓抑制是恶性肿瘤放化疗中的常见不良反应之一。中医药在治疗放化疗所致的骨髓抑制中具有效果明确、不良反应小的优点。人参固本口服液由千古名方六味地黄丸与人参固本丸合方而成,是治疗放化疗骨髓抑制的有效药物。现从人参固本口服液的组方结构、功效特点和现代药理研究探究其治疗放化疗骨髓抑制的机制,以期为人参固本口服液在放化疗骨髓抑制防治中的应用提供理论指导。     

不可手术或术后残存或复发胃癌的尼妥珠单抗联合卡培他滨同步放化疗前瞻性研究

目的 探索尼妥珠单抗联合卡培他滨同步放化疗治疗不可手术或术后残存或复发胃癌患者的不良反应和近期疗效。方法 对病理确诊的胃癌患者开展前瞻性Ⅱ期试验,入组条件:有可测量病变的不可手术或术后残存或复发胃癌,病变可行放疗,预期生存>3个月。患者接受IMRT (PGTV 54 Gy分30次,±淋巴结预防区域45 Gy分25次)和同步卡培他滨(每天1 600 mg/m²,第1—35天)及尼妥珠单抗(200 mg,1 次/周)化疗。用CTCAE3.0和RECIST标准评估急性不良反应和近期疗效。结果 2010—2013年纳入30例患者。中位年龄57岁(35~66岁)。23例为术后残存或复发,7例为不可手术患者。28例入组前接受化疗且均为疗后稳定或进展。同步放化疗期间5例(17%)3级急性不良反应,主要为血小板下降(10%)。疗后1个月野内客观缓解率和病变稳定率、全身客观缓解率和病变稳定率分别为43%(CR 4%、PR 39%)和50%、32%和43%。结论 对不可手术或术后残存或复发胃癌患者,尼妥珠单抗联合卡培他滨同步放化疗安全,耐受性、近期疗效、放疗野内控制性均好。临床试验注册 ClinicalTrials.gov,注册号:NCT01180166。     

局部进展期直肠癌新辅助放化疗的研究进展

术前放化疗联合全系膜切除手术为局部晚期直肠癌患者治疗的标准模式,术前放化疗比术后放化疗提高了肿瘤降期率、保肛率及局部控制率,术前放化疗后达到病理完全缓解患者拥有更好的预后。本文就近年来术前放化疗的研究进展作一综述。     

Ⅱ和Ⅲ期直肠癌术后卡培他滨±奥沙利铂同步放化疗急性副反应比较

目的 比较两个前瞻性非随机对照直肠癌术后同步放化疗临床Ⅱ期研究的急性毒副反应及耐受性.方法 2005年3月至2007年11月分别进行卡培他滨术后同步放化疗(单药组,n=118)和奥沙利铂+卡培他滨术后同步放化疗(双药组,n=90)的Ⅱ期临床研究.两组均予真骨盆放疗DT50 Gy分25次5周完成,化疗药物予以连用2周停1周,放疗中共用2周期的方法 .单药组卡培他滨每天2次1600 mg/m2双药组奥沙利铂每周1次70 mg/m2,卡培他滨每天2次1300 mg/m2.结果 双药组患者中断放疗(10.2%:6.7%,X2=0.80,P=0.460)或化疗的比率(9.3%:19.1%,X2=4.80,P=0.090)与单药组相似.双药组1～4级急性非血液学毒副反应发生率显著高于单药组,主要为恶心(X2=46.90,P=0.000),腹泻(X2=13.50,P=0.009),乏力(X2=18.90,P=0.000),手足综合症(X2=7.10,P=0.029)和食欲下降(X2=19.90,P=0.000).全组发生3、4级以上严重副反应包括腹泻(24.0%、1.0%)、白细胞下降(4.3%、0.0%)、放射性皮炎(3.8%、0.0%)、腹痛(1.0%、0.0%)和乏力(0.5%、0.0%),但只有3、4级腹泻发生率双药组显著高于单药组(33.0%:18.6%,X2=5.90,P=0.023).结论 接受奥沙利铂+卡培他滨双药同步放化疗患者3、4级腹泻发生率显著高于卡培他滨单药同步放化疗,但其他严重副反应发生率低且两组相似.     

Double blind randomized phase II study with radiation + 5-fluorouracil ± celecoxib for resectable rectal cancer

Purpose

To assess the feasibility and efficacy of the COX-2 inhibitor celecoxib in conjunction with preoperative chemoradiation for patients with locally advanced rectal cancer in a double blind randomized phase II study.

Materials and methods

Thirty-five patients of the initially planned 80 patients with locally advanced rectal cancer were treated with preoperative radiation (45 Gy; 1.8 Gy/fraction, 5 days/week) combined with 5-fluorouracil (continuous infusion, 225 mg/m²/day) and celecoxib (2 × 400 mg/day) or placebo. Pathological response and toxicity of study treatment were evaluated, as well as expression of COX-2 and Ki67 in tumor tissue and IL-6 in plasma as possible molecular correlates and predictors of response to treatment.

Results

Patients treated with celecoxib tended to show a better response (61%) when compared to those treated with placebo (35%), although not significant (p = 0.13). T-downstaging and N-downstaging were also slightly higher with celecoxib. Plasma IL-6 levels and intratumoral COX2 or Ki67 were altered by chemoradiation, but were not further altered by celecoxib treatment and therefore not useful for prediction of treatment benefit. Celecoxib therapy in conjunction with chemoradiation was not associated with additional toxicity and seemed to help mitigate therapy-related pain.

Conclusions

Addition of celecoxib to preoperative chemoradiation is feasible for patients with locally advanced rectal cancer. To study the individual effect of COX-2 inhibitors on pathological response phase III studies are required.     

胰腺癌的放射治疗进展

胰腺癌高度恶性,手术可切除率低.放射治疗通过射线作用于肿瘤细胞DNA,引起细胞死亡以达到治疗目的,将其与化学治疗相联合的辅助治疗,对胰腺癌的综合治疗具有重要意义.该文回顾了近年来放射治疗在胰腺癌术前新辅助治疗、术后辅助治疗以及局部进展期治疗等方面取得的进展.放、化疗联合治疗对于不可切除胰腺癌病例的治疗意义尚需要更多更为可靠的循证医学证据来明确.     

Radiation therapy in the elderly: More side effects and complications?

Aging is associated with physiological changes and comorbid illnesses, which may affect an individual's tolerance to radiation. There is the belief that a relationship exists between age and radiation toxicity and therefore non-curative schemes are offered to older patients. Preclinical studies show that normal tissue radiation-induced toxicity differs little with age. In the clinical setting, retrospective and some prospective studies have reported that elderly patients treated with radical radiotherapy alone or in combination with chemotherapy, who do not have comorbidities and retain a good performance status, show a benefit in treatment outcomes. However, an increase in acute effects or a lowered functional tolerance has also been reported. To select candidates for radical treatments, a specific geriatric assessment should be used to stratify elderly patients as a function of the physiological status. Only specifically designed prospective studies can define the role of radiation treatment in elderly patients with different physiological status.     

Ⅱ、Ⅲ期直肠癌根治术后不同氟脲嘧啶联合放化方案效果比较

目的比较三种不同氟脲嘧啶联合放化方案在Ⅱ、Ⅲ期直肠癌根治术后辅助治疗的疗效及不良反应。方法对2005年11月至2008年2月对我科收治的43例Ⅱ、Ⅲ期直肠癌随机分组：AmA放疗第1～5,29～33天静脉推注5-氟尿嘧啶（5-FU）250mg／（m^2·d）,5-FU之前使用亚叶酸钙（OF）200mg／（m^2·d）增敏,同时盆腔放疗;ArmB放疗第1～5,29～33天持续静脉泵注5．氟尿嘧啶（5-FU）700mg／（m^2·d）,同时盆腔放疗;ArmC放疗第1～14,22～35天口服卡培他滨1600mg／（m^2·d）,同时盆腔放疗50Gy。序贯FOLFOX4方案全身化疗6个周期。结果ArrnAIArmB和ArmC三组两年0s分别为86％、89％和92％（P〉0．05）,两年DFS分别为64％、69％和77％（P〉0．05）。放化各组3～4级急性毒副反应不同,ArmA主要为骨髓抑制,ArmB主要为3～4级放射性直肠炎或手足综合征,ArmC副反应较轻。结论三种不同氟脲嘧啶联合放化治疗0s差异无统计学意义,希罗达联合放疗组具有延长D鹏的趋势。三种不同氟脲嘧啶联合放化均安全可耐受,希罗达联合放疗组毒副反应较轻。