Xelox方案与替吉奥联合奥沙利铂治疗68例晚期结直肠癌病例疗效及不良反应研究

目的 探讨卡培他滨联合奥沙利铂(Xelox)与替吉奥联合奥沙利铂两种治疗方案对晚期结直肠癌的临床疗效及不良反应比较,为临床应用提供理论和实践的依据。方法 选取68例符合入组标准的晚期结直肠癌患者,随机分成卡培他滨联合奥沙利铂治疗组为(A组)35例,替吉奥联合奥沙利铂方案(B组) 33例,通过观察两组方案的近期疗效、疾病进展时间及不良反应,分析评价两种方案的临床效果。结果 两种方案的近期疗效、疾病进展时间和不良反应发生情况,差异均无有统计学意义(P>0.05)。结论 卡培他滨联合奥沙利铂与替吉奥联合奥沙利铂治疗晚期结直肠癌疗效相当,不良反应无明显差异,两种方案均可作为晚期结直肠癌患者治疗的较好选择。     

Oral drugs in the treatment of metastatic colorectal cancer

Introduction: Intravenous administration of fluoropyrimidine-based chemotherapy has been the cornerstone of treatment in metastatic colorectal cancer (mCRC) for decades. The availability of oral capecitabine has improved the tolerability in monotherapy schedules, and has simplified combination schedules. Since then, other oral drugs have proven efficacy in this setting.

Areas covered: We review the available evidence and most recent data concerning oral drugs with proven efficacy in mCRC, including capecitabine, S-1, trifluridine-tipiracil (TAS-102) and regorafenib.

Expert opinion: The use of capecitabine is widely implemented in the care of mCRC. However, with recent data supporting its prolonged use, the relatively high incidence of hand-foot syndrome (HFS) may impair quality of life. In Asian populations, S-1 is associated with equivalent efficacy but lower incidence of HFS compared to capecitabine. Further studies evaluating the effects of S-1 in Western populations are needed. Both regorafenib and TAS-102 improve the overall survival of patients in whom all other treatment options have failed. Since only a subset of patients appears to benefit, future studies to identify predictive biomarkers are needed.     

Neo‐adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource‐poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

The majority of clinical trials of neo‐adjuvant therapy for breast cancer have been conducted in resource‐rich countries. We chose Nigeria, a resource‐poor country, as the major site for a phase II feasibility open‐label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo‐adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m² twice daily (2,000 mg/m² total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11–59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20–70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand–foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo‐adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.     

Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.     

The Effects of Phyllanthus niruri Linn on Infiltrating Dendritic Cell and Ratio of Neutrophile/Lymphocytes in Chemotherapy of Sprague-Dawley Rats with Colorectal Cancer

Background: Chemotherapy as part of colorectal cancer management can cause death to immunologically active tumor cell, but also it has immune suppressive effect. Phyllanthus niruri Linn is known to has immunomodulatory effect. This study was intended to prove P. niruri Linn effect on infiltrating dendritic cells and Neutrophil/lymphocyte ratios (NLRs) in Sprague–Dawley rats with colorectal cancer which were given capecitabine chemotherapy. Methods: The study was randomized post–test only control group design. The samples were 39 Sprague–Dawley male rats, with body weight around 170–220 grams, induced by 1,2-dimetylhydrazine (DMH) 30 mg/kgBW once per week subcutaneously. On 9th,11th and 13th week, there were four induced rats sacrificed each week to detect colorectal cancer (CRC) development. On the 13th week, all of the 4 sacrificed rats developed colon cancer, so the induction had to be stopped. The rest of 27 induced rats were randomly divided into three groups: control-group (K) were left untreated (9 rats), group P1 (9 rats) were given Capecitabine and group P2 (9 rats) were given Capecitabine with combination of P. niruri Linn extract 13.5 mg/kgBW orally. After 17th week, all rats were terminated and tumor lesion of colon were processed to be paraffin blocks and were stained with HE for evaluating the NLRs, and immunohistochemistry (S100) for evaluating infiltrating dendritic cells. Data was analyzed by using Oneway-Anova-test and post-Hoc LSD-test. Considered significant if p was <0.05. Results: The mean±standard deviation of infiltrating dendritic cells showed increasing value in group P2 (62.11±31.35) compared to group P1 (52.78±29.24) though not statistically significant. The mean of NLRs also showed statistically significant elevation of value in group P2 (0.13±0.05) compared to group P1 (0.04±0.01). Conclusion: Extract of Phyllanthus niruri Linn increasing immunologic status through elevation of infiltrating dendritic cells and NLRs in animal model colorectal cancer with Capecitabine chemotherapy.     

卡培他滨维持治疗转移性结肠、直肠癌的疗效及安全性观察

目的评价卡培他滨维持治疗以延长转移性结肠、直肠癌一线化疗后的无疾病进展时间（TTP）的疗效及安全性。方法 50例转移性结肠、直肠癌患者一线化疗后达到稳定,按患者意愿分成2组,治疗组（n=30）给予单药卡培他滨口服,2次/d,餐后服用,2 500 mg/（m2.d）,连续服用14 d后停药7 d,治疗周期为21 d,至少治疗2个周期,直至病情进展或毒性不能耐受;对照组（n=20）采用持续化疗,定期监测,直至病情进展。结果治疗组中位TTP（mTTP）为9.2个月,中位疾病控制时间（mDDC）13.7个月;对照组mTTP为6.1个月,mDDC为9个月,2组mTTP、mDDC差异均有统计学意义。治疗组不良反应多数为Ⅰ~Ⅱ级。结论转移性结肠、直肠癌患者在一线化疗达到稳定后给予单药卡培他滨维持化疗,可显著延长患者TTP,且耐受性良好。     

多西他赛联用替吉奥或卡培他滨治疗胃癌的成本—效果分析

目的比较替吉奥与卡培他滨分别联合多西他赛(TXT)治疗进展期胃癌的有效性、安全性及经济效果。方法试验分A、B两组,第1天均给予多西他赛75 mg/m2,静脉滴注2 h;第1～14天,A组每天给予卡培他滨2 000 mg/m2,B组每天给予替吉奥胶囊60 mg/m2,两组给药均分为两等份于早晚餐后0.5 h用水吞服,服用2周后休息1周,3周为1个周期,至少完成2个周期,最多完成6个周期后评价。结果 50例均可评价疗效。A、B两组的总有效率分别为46.21%和50.00%,疾病控制率为76.92%和75.00%(P>0.05),平均成本分别为17 158.90元和10 094.37元。成本–效果比分别为371.81和201.89。两组不良反应主要包括骨髓抑制、恶心呕吐、腹泻、口腔黏膜炎和手足综合征等,以1～2级为主,均可耐受。结论两组治疗晚期胃癌的疗效相当,不良反应均可耐受,但B组成本–效果明显低于A组,因此替吉奥联合多西他赛治疗进展期胃癌方法更优,值得临床推广。     

Identification of novel germline polymorphisms governing capecitabine sensitivity

BACKGROUND:

Capecitabine, an oral 5‐fluorouracil (5‐FU) prodrug, is widely used in the treatment of breast, colorectal, and gastric cancers. To guide the selection of patients with potentially the greatest benefit of experiencing antitumor efficacy, or, alternatively, of developing toxicities, identifying genomic predictors of capecitabine sensitivity could permit its more informed use.

METHODS:

The objective of this study was to perform capecitabine sensitivity genome‐wide association studies (GWAS) using 503 well genotyped human cell lines from individuals representing multiple different world populations. A meta‐analysis that included all ethnic populations then enabled the identification of novel germline determinants (single nucleotide polymorphisms [SNPs]) of capecitabine susceptibility.

RESULTS:

First, an intrapopulation GWAS of Caucasian individuals identified reference SNP 4702484 (rs4702484) (within adenylate cyclase 2 [ADCY2]) at a level reaching genome‐wide significance (P = 5.2 × 10^?8). This SNP is located upstream of the 5 methyltetrahydrofolate‐homocysteine methyltransferase reductase (MTRR) gene, and it is known that the enzyme for MTRR is involved in the methionine‐folate biosynthesis and metabolism pathway, which is the primary target of 5‐FU‐related compounds, although the authors were unable to identify a direct relation between rs4702484 and MTRR expression in a tested subset of cells. In the meta‐analysis, 4 SNPs comprised the top hits, which, again, included rs4702484 and 3 additional SNPs (rs8101143, rs576523, and rs361433) that approached genome‐wide significance (P values from 1.9 × 10^?7 to 8.8 × 10^?7). The meta‐analysis also identified 1 missense variant (rs11722476; serine to asparagine) within switch/sucrose nonfermentable‐related, matrix‐associated, actin‐dependent regulator of chromatin (SMARCAD1), a novel gene for association with capecitabine/5‐FU susceptibility.

CONCLUSIONS:

Toward the goal of individualizing cancer chemotherapy, the current study identified novel SNPs and genes associated with capecitabine sensitivity that are potentially informative and testable in any patient regardless of ethnicity. Cancer 2011. © 2011 American Cancer Society.     

塞来昔布联合卡培他滨节拍化疗治疗老年患者晚期结肠癌的疗效观察

目的 探讨塞来昔布联合卡培他滨节拍化疗治疗老年患者晚期结肠癌的临床疗效。方法 回顾性研究35例老年晚期结肠癌病例,所有患者均给予口服卡培他滨500 mg,2次/d,塞来昔布200 mg,2次/d,连续服药直至病情进展,至少2月后评价疗效以及毒副反应。结果 治疗总有效率为37.1%,疾病控制率为77.1%,生活质量总改善率82.9%,中位疾病进展时间为8个月,中位生存期为14个月。所有患者均以Ⅰ、Ⅱ级毒副反应为主,主要为白细胞减少、手足综合征、恶心呕吐、腹泻、食欲减退等。结论 塞来昔布联合卡培他滨节拍化疗治疗老年晚期结肠癌具有安全、有效、毒副反应小以及患者依从性好等优点。