紫杉醇联合希罗达治疗晚期胃癌的初步观察

目的 观察联合希岁达与紫杉醇治疗晚期胃癌的疗效与毒副反应。方法 对68例晚期胃癌患者进行回顾性统计分析。结果 CR6％，PR47％，NC22％，PD25％。症状缓解率81％。一年总生存率72％。平均缓解时间5．5月。化疗副反应包括恶心呕吐（86％），手足综合征（45％）；Ⅰ、Ⅱ度骨髓抑制（55％）及Ⅲ、Ⅳ度骨髓抑制（12％）；无化疗相关死亡。结论 希罗达加紫杉醇方案对晚期胃癌疗效较好，毒副作用较轻。     

紫杉醇联合草酸铂、卡培他滨三药方案治疗晚期转移性鼻咽癌的临床研究

目的探讨紫杉醇联合草酸铂、卡培他滨三药方案治疗晚期转移性鼻咽癌的疗效及不良反应。方法2002年1月至2005年1月，110例晚期转移性鼻咽癌病人入组：试验组55例患者．第1天应用紫杉醇135mg／m^2、草酸铂130mg／m。静脉滴注，口服卡培他滨1650mg／m^2／d，连服l-14d，每3周为一个周期，连用2-4个周期；对照组55例患者，第1-5天应用DDP 20mg／m^2、5-Fu 0．5g／m^2静脉注射，3周为一个周期，连用2-4个周期；治疗结束2-4周后评价疗效。结果试验组疗效可评价55例，对照组疗效可评价53例。试验组与对照组有效率分别为（CR＋PR）50．9％（28例）和32．1％（17例），两者差异有统计学意义（P〈0．05）。试验组和对照组中位生存时间为10．6个月和8．6个月，两者差异有统计学意义（t〈0．05）。安全性方面：试验组Ⅳ反应主要为手足综合征8例（14．5％）、骨髓抑制2例（3．6％）和消化道毒性4例（7.3％）；对照组Ⅳ反应主要为消化道毒性8例（15.1％）、骨髓抑制2例（3.8％）。结论紫杉醇联合草酸铂、卡培他滨三药方案对晚期转移性鼻咽癌的疗效较DDP＋5-Fu有优势，且不良反应可以耐受。     

Effect of Jianpi Bushen formula for colon cancer patients who underwent adjuvant chemotherapy: Statistical analysis plan for a multicenter trial

BackgroundPatients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea, which make it challenging for them to adhere to treatment. As an effective traditional Chinese medicine, the Jianpi Bushen formula has been widely used to alleviate the side effects of chemotherapy.ObjectiveTo evaluate the efficacy and safety of Jianpi Bushen formulae for patients who undergo chemotherapy. This statistical analysis plan (SAP) is intended to enhance the transparency and research quality of our randomized controlled trial.MethodsOur study is a multicenter, double-blind, randomized controlled clinical trial. This trial aimed to compare the completion rate of chemotherapy in colon cancer patients who are using and not using Jianpi Bushen formula. To attenuate possible selection bias in the final report, we declared the overall trial design, outcome measures, subgroup analyses, and safety measures. Also, we described the data management and statistical analysis methods in detail.ConclusionThe SAP provides more detailed information than the trial protocol for data management and statistical analysis methods. Further post-hoc analyses can be performed by referring to the SAP, and possible selection bias can be attenuated.     

卡培他滨治疗消化道恶性肿瘤的药物经济学评价

目的 :提供卡培他滨治疗消化道恶性肿瘤的药物经济学评价依据。方法 :比较卡培他滨单药口服和5 -氟尿嘧啶 +亚叶酸 +奥沙利铂 (FOLFOX4)方案治疗消化道恶性肿瘤的疗效、不良反应、直接医疗费用和间接费用 ,并以最小成本分析法进行药物经济学评价。结果 :卡培他滨组与FOLFOX4组疗效相近 ,分别为30. 3 %、38. 9 % (P>0. 05 ,X2=0. 45) ,病灶稳定率分别为42 5 %、32. 4 % ,而每个疗程住院天数卡培他滨组明显少于FOLFOX4组 ,分别为8 5天、25. 3天 (P=0.000) ,且每个疗程医疗总费用卡培他滨组也明显低于FOLFOX4组 ,分别为5941 7元、13304. 6元 (P=0 001)。经费用结构分析显示 ,与卡培他滨组比较 ,FOLFOX4组的直接医疗费用和间接费用增加都非常明显 (P=0.001) ;不良反应发生率卡培他滨组也较低。结论 :从药物经济学角度看 ,在消化道恶性肿瘤的治疗中卡培他滨口服方案优于FOLFOX4方案。     

A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma

Lessons Learned

• A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies.
• This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.

BackgroundThis study aimed to evaluate efficacy and safety of capecitabine combined with a PHY906 (a pharmaceutical‐grade formulation of four traditional Chinese herbs) in the treatment of advanced hepatocellular carcinoma (HCC) in Asian patients who were positive for hepatitis B virus (HBV).MethodsThis study was an open‐label, phase II safety and efficacy clinical trial of PHY906 and capecitabine in patients with advanced HCC. Patients received 750 mg/m² capecitabine b.i.d. 14 days plus 800 mg of PHY906 b.i.d. on days 1–4 and days 8–11 every 21‐day cycle. The primary endpoint was 6‐month survival rate, and secondary endpoints were progression‐free survival, overall survival, disease control rate, and safety.ResultsThirty‐nine subjects completed the study with a 46.2% stable disease rate. The median progression‐free survival was 1.5 months, and median overall survival (mOS) was 6 months with a 51.3% 6‐month survival rate. The most common adverse events included lower hemoglobin, diarrhea, pain, abdomen (not otherwise specified), fatigue, increased aspartate aminotransferase, and bilirubin. Patients who (a) had not received previous chemotherapies or targeted therapy or (b) had lower starting alpha‐fetoprotein (AFP) levels or (c) had HBV infection showed better clinical outcome.ConclusionOur data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC.     

Subacute reversible toxic encephalopathy related to treatment with capecitabine: A case report with literature review and discussion of pathophysiology

IntroductionCapecitabine, a 5-fluorouracil (5FU) pro-drug, is increasingly used in breast and gastrointestinal cancers due to its more convenient oral route of administration when compared to 5FU. Despite its widespread use, there are only a few reports on capecitabine CNS toxicity, while the pathogenic basis of such toxicity remains unclear.CaseA 69-year-old male presented with recurrent generalized seizures 2.5 months after preoperative chemoradiotherapy with capecitabine in locally advanced rectal cancer. Brain MRI revealed a diffuse, subcortical white matter alteration suggestive of vasogenic edema. The diagnosis of toxic encephalopathy was supported after elimination of alternative causes of the neurological dysfunction and complete resolution of clinical and imaging findings after 3 months of no further chemotherapy.ConclusionsGiven the expanding use of capecitabine, physicians should be aware of this potential complication when a neurological worsening occurs during or after treatment with this chemotherapeutic agent. In our case, as in previously described cases encephalopathy was characterized by a favorable course after cessation of the drug. Vasogenic edema rather than cytotoxic edema may play a pivotal pathogenetic role in this form of encephalopathy.     

Prospective DPYD genotyping to reduce the risk of fluoropyrimidine-induced severe toxicity: Ready for prime time

5-Fluorouracil (5-FU) and capecitabine (CAP) are among the most frequently prescribed anticancer drugs. They are inactivated in the liver by the enzyme dihydropyrimidine dehydrogenase (DPD). Up to 5% of the population is DPD deficient and these patients have a significantly increased risk of severe and potentially lethal toxicity when treated with regular doses of 5-FU or CAP. DPD is encoded by the gene DPYD and variants in DPYD can lead to a decreased DPD activity. Although prospective DPYD genotyping is a valuable tool to identify patients with DPD deficiency, and thus those at risk for severe and potential life-threatening toxicity, prospective genotyping has not yet been implemented in daily clinical care. Our goal was to present the available evidence in favour of prospective genotyping, including discussion of unjustified worries on cost-effectiveness, and potential underdosing. We conclude that there is convincing evidence to implement prospective DPYD genotyping with an upfront dose adjustment in DPD deficient patients. Immediate benefit in patient care can be expected through decreasing toxicity, while maintaining efficacy.     

The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis

IntroductionBreast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs.Material and methodsWe searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and the European Union Clinical Trials Register for studies reporting data on L, singly or in combination with C, for the treatment of HER-2+ BC with BMs. Primary end-points were overall response rate (ORR) and disease control rate (DCR); these were pooled to provide an aggregate value. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Data were pooled using number of events/number of evaluable patients, according to a fixed or random effect model.ResultsOverall, 12 studies were included in the present meta-analysis, for a total of 799 patients with BMs. The pooled overall response rate (ORR) was 21.4% (95% CI 11.7–35.9). After exclusion of patients that received L alone, ORR reached 29.2% (95% CI 18.5–42.7). The pooled median PFS and OS were 4.1 (95% CI 3.1–6.7) and 11.2 (95% CI 8.9–14.1) months, respectively.ConclusionsDue to its activity on BMs, the L + C combination may be considered for HER-2+ BC that has progressed in the brain, when local therapy has been performed or failed and re-irradiation is not feasible.