Oral capecitabine as postoperative adjuvant chemotherapy in stage III colon cancer patients

Capecitabine(Xeloda?)has been a global standard drug for the treatment of colon cancer since large randomized controlled trials demonstrated its efficacy and safety in treating patients suffering from the disease. Few studies have been conducted to assess the effects of oral capecitabine treatment on Japanese patients. Therefore, we conducted this study to evaluate oral capecitabine as postoperative adjuvant chemotherapy in 50 patients who underwent surgery for stage III colon cancer at our department. Patients received an 8 courses treatment with capecitabine during the study, and the incidence of adverse events, treatment completion rate, and treatment compliance were assessed. Adverse events were reported in a total of 46 patients(92%). The most common adverse event was hand foot syndrome(HFS), reported in 39 patients(78%), whereas bone-marrow toxicity and diarrhea were reported in as few as 2(4%)and 3(6%)patients, respectively. Both these events were mild in severity, and no patients required hospitalization, nor were they associated with treatment-related deaths. The median treatment duration was 8 courses ranging from 3 to 8 courses, and the 8 courses treatment completion rate was 96%. The relative dose intensity, which was used as a treatment compliance index, is expressed as the actual dose taken by the patient divided by the dose planned at baseline. The median and mean of the relative dose intensity were 100%(ranging from 37% to 100%)and 93%, respectively. The results of this study showed that the safety profile of oral capecitabine therapy was generally favorable, with a lower incidence and lesser severity of life-threatening bone-marrow toxicity and diarrhea, although the treatment is still associated with frequent HFS. This is the great advantage of capecitabine when it is used as postoperative adjuvant chemotherapy for gastrointestinal cancer. Indeed, a satisfactory treatment completion rate was achieved in this study while maintaining a sufficient dose and treating HFS, by reducing the dose, interrupting treatment, or providing appropriate corrective measures.     

Cost-effectiveness of oxaliplatin and capecitabine in the adjuvant treatment of stage III colon cancer

For many years, the standard treatment for stage III colon cancer has been surgical resection followed by 5-fluorouracil in combination with folinic acid (5-FU/LV). Ongoing clinical trial evidence suggests that capecitabine and oxaliplatin (in combination with 5-FU/LV) may improve disease-free survival and overall survival when compared against 5-FU/LV alone in the adjuvant setting. This study evaluates the cost-effectiveness profiles of these two regimens in comparison to standard chemotherapy, using evidence from two international randomised controlled trials. Survival modelling techniques were employed to extrapolate survival curves from the two trials in order to estimate the long-term benefits of alternative treatment options over the remaining lifetime of patients. The health economic analysis suggests that capecitabine is expected to produce greater health gains at a lower cost than 5-FU/LV. Oxaliplatin in combination with 5-FU/LV is estimated to cost pounds 2970 per additional QALY gained when compared to 5-FU/LV alone. Future research should attempt to elucidate uncertainties concerning the optimal roles of capecitabine and/or oxaliplatin in the adjuvant setting in order to achieve the maximum level of clinical benefit.     

卡培他滨辅助治疗结肠癌的研究进展

结直肠癌是最常见的恶性肿瘤之一,据统计,2007年全球新发病例120万,居恶性肿瘤第3位,同年死亡病例为60万.手术切除是治愈结直肠癌最好的手段,而术后辅助化疗能减少复发和转移风险,进一步提高疗效.除传统药物5-氟尿嘧啶(5-Fu)外,近年来,出现了很多被证明对结肠癌有确实疗效的药物,如卡培他滨、伊立替康和奥沙利铂,这些药物都在全球范围内进行并完成了结肠癌的临床试验,其中卡培他滨和奥沙利铂被证明应用于辅助治疗有效.这些循证医学的证据使得结肠癌的辅助化疗发生了很大的变化,并趋于规范.本文在循证医学证据的基础上,就结肠癌的辅助治疗,尤其是卡培他滨应用方面的进展进行回顾.     

替吉奥及卡培他滨联合奥沙利铂一线治疗晚期大肠癌的近期疗效比较

目的 比较替吉奥联合奥沙利铂(SOX方案)与卡培他滨联合奥沙利铂(XELOX方案)一线治疗晚期大肠癌的有效性和安全性.方法 53例晚期大肠癌患者按拆信封法分为两组,SOX方案组26例,奥沙利铂130 mg/m2静脉滴注3h,第1天;替吉奥40 mg/ m2分早晚2次餐后口服,第1天至第14天,3周为1个周期.XELOX方案组27例,奥沙利铂130 mg/m2静脉滴注3h,第1天;卡培他滨1000 mg/m2分早晚2次餐后口服,第1天至第14天,3周为1个周期.2个周期评价疗效及毒性.结果 53例均可评价疗效,SOX方案组、XELOX方案组的有效(RR)率分别为46.1％(12/26)和48.1％(13/27),疾病控制率为76.9％(20/26)和74.1％(20/27),两组RR差异均无统计学意义(x2=0.013,P=0.909).两组不良反应主要包括血液学毒性、肝肾功能异常、恶心呕吐、腹泻、末梢神经毒性和手足综合征等,以Ⅰ～Ⅱ级为主,均可耐受,其中SOX方案组的恶心呕吐发生率[61.5％(16/26)]明显高于XELOX方案组[33.3％(9/27)](x2=4.462,P=0.035),但XELOX方案组的腹泻、手足综合征发生率[均44.4％(12/27)]则明显高于SOX方案组[19.2％(5/26)、3.8％(1/26)](x2=4.366、P=0.037,x2=11.699、P=0.001).结论 替吉奥联合奥沙利铂与卡培他滨联合奥沙利铂治疗晚期大肠癌的疗效相当,不良反应均可耐受.     

肠道支架植入术后卡培他滨联合恩度治疗晚期结肠癌的临床研究

目的  探讨卡培他滨联合重组人血管内皮抑制素（恩度）治疗肠道支架植入术后的晚期结肠癌患者的疗效及安全性。方法  选取2010年1月至2017年1月收治的不能手术切除且伴肠梗阻的晚期结肠癌患者79例,根据其后续治疗方案分为治疗组（39例）和对照组（40例）。所有患者入院后均行肠道支架植入术,解除肠梗阻后,治疗组给予卡培他滨联合恩度治疗,对照组给予卡培他滨单药治疗。治疗周期结束后比较两组的近期疗效和不良反应,并随访两组的无疾病进展生存期和总生存期。结果  所有患者均成功植入肠道支架解除肠梗阻,并完成化疗计划。治疗组患者的总有效率较对照组高,但差异无统计学意义（46.15% vs 30.00%,χ²=2.921,P=0.087）;治疗组疾病控制率亦高于对照组,差异有统计学意义（69.23% vs 50.00%,χ²=3.978,P=0.046）。两组患者化疗及肠道支架植入术相关不良反应发生率相当 （P>0．05）。治疗组中位无疾病进展生存期较对照组延长3个月（16个月 vs 13个月,P＜0.05）,中位总生存期延长6个月（25个月 vs 19个月,P＜0.05）。结论  肠道支架植入术可有效解除结肠癌患者肠梗阻,后续卡培他滨联合恩度治疗的疗效优于卡培他滨单药治疗,且未增加不良反应,患者可耐受。     

Anti-angiogenesis participates in antitumor effects of metronomic capecitabine on colon cancer

Inhibitory effects and potential mechanisms of capecitabine metronomic chemotherapy on colon cancer were investigated in this study. Metronomic chemotherapy with fluorouracil or capecitabine inhibited proliferation of colon cancer cells both in vitro and in vivo. Capecitabine metronomic chemotherapy demonstrated equal effects as CTX metronomic chemotherapy. Metronomic capecitabine or CTX chemotherapy decreased vascular endothelial growth factor (VEGF) but elevated thrombospondin-1 (TSP-1) expression, reduced CEP levels and decreased microvessel density (MVD). These results indicated anti-angiogenesis may be correlated with the antitumor effects of metronomic capecitabine in colon cancer.     

Oral capecitabine in anthracycline- and taxane-pretreated advanced/metastatic breast cancer

An open-label, non-randomized, compassionate-use study was carried out to investigate the effects of oral capecitabine at a dose of 1 250 mg/m2 twice daily on days 1 to 14 every 21 days in anthracycline- and taxane-pretreated advanced/metastatic breast cancer patients. Forty-eight patients were enrolled from April 2000 to December 2001. Twenty-four patients (50%) had metastases to the liver, 18 to bone, 13 to lung, 10 to regional lymph nodes, 8 to pleura, 7 to the thoracic wall, 5 to skin, 3 to the mediastinum, 1 to breast and 1 had metastasis to the abdomen. Thirty-three patients (69%) had metastases to more than one site. Median age of the patients was 55 years (range 35-74). Three patients had an ECOG performance status (PS) of 0, 32 PS 1 and 13 PS 2, respectively. Fourteen patients (29%; 95% CI 16 to 42%) obtained a partial response (PR) while 16 (33%) had stable disease (SD) as the best response, of whom 6 had stabilization for more than 24 weeks. This gives a clinical benefit (PR + SD > 24 weeks) of 42% (95% CI 28 to 56). Dose reduction was necessary in 29% of the patients. Median dose reduction was 25%. Grades 2 and 3 hand-foot syndrome (PPE) was observed in 17 patients (36%). Eleven patients experienced grades 2 and 3 gastrointestinal toxicity, and haematological toxicity grade 3 was observed in 3 patients (6%). Median time to progression was 107 days (CI 95% 85 to 129), and median overall survival was 281 days (CI 95% 164 to 398). Third-line, oral capecitabine in anthracycline- and taxane-pretreated metastatic breast cancer appears to be effective and has an acceptable toxicity profile.     

Oral fluoropyrimidines in the adjuvant therapy of colon cancer

Oral chemotherapy offers several potential benefits over intravenous treatment, and the majority of patients would prefer oral therapy provided that it does not compromise efficacy. We review the evidence that oral fluoropyrimidines can replace intravenous 5-fluorouracil (5-FU) in the adjuvant therapy of colon cancer, without loss of efficacy, while at the same time improving tolerability and reducing the use of medical resources. The addition of oxaliplatin to intravenous 5-FU improves disease-free survival in patients with resected colon cancer and both uracil/tegafur and capecitabine can be combined safely with oxaliplatin. The effect on efficacy of replacing intravenous 5-FU with oral fluoropyrimidines in combination regimens is being assessed in ongoing trials.     

草酸铂联合卡培他滨方案治疗食管癌转移瘤的疗效观察

目的:探讨应用草酸铂(L-OHP)与卡培他滨联合方案治疗食管癌转移瘤患者的疗效及安全性,并随访观察中位至疾病进展时间和中位总生存时间.方法: 48例食管癌转移瘤患者使用草酸铂130mg/m2,静脉滴注,第1天;卡培他滨1000 mg/m2口服,每日2次,第1-14天;每3周为一个周期,至少应用2周期,评价疗效和毒性,并进行随访.结果: 48例患者疗效均可评价,完全缓解(CR)2例(4.2%),部分缓解(PR)16例(33.3%),稳定(SD)23例(47.9%),进展(PD)7例(14.6%).有效率(CR PR)为37.5%.中位无进展生存期4.5个月,中位生存期8个月.化疗中主要毒副反应为骨髓抑制、消化道反应、神经毒性等.结论: 草酸铂联合卡培他滨治疗食管癌转移瘤疗效肯定,毒副反应能耐受,值得进一步研究.     

Oral cancer treatment

Opinion statement Oral cancer is the sixth most common cancer in the world, and it continues to represent a serious public health problem. Oral cancer is a preventable disease, related to behavioral and lifestyle factors, including tobacco and alcohol. Prevention and early detection of oral cancer remain the goals of national efforts to reduce the impact of this disease on the public. Surgical treatment is the mainstay of therapy for patients with oral cancer, particularly in advanced stages of cancer. External beam radiation therapy and brachytherapy have been used successfully as the primary modality for treating patients with early stage oral cancer, and they are the standard of care for use as adjuvant therapy in postoperative cases of patients with advanced stage oral cancer. There is an emerging trend for the use of chemotherapy in combination with radiation therapy and surgery for patients with advanced, recurrent, and metastatic head and neck cancer, although evidence is limited regarding survival benefit when used for treating patients with oral cavity carcinoma. Any report on the treatment of oral cancer is incomplete without consideration of functional and aesthetic outcomes, particularly addressing speech, swallowing, masticatory efficiency, and dental rehabilitation. Future generations will continue to fight these dreadful diseases until scientists and clinicians are provided the opportunities to expand efforts to prevent, detect (early), and eradicate oral and other head and neck cancers.     

Adjuvant capecitabine chemotherapy using a tailored-dose strategy in elderly patients with colon cancer

BackgroundThis study was conducted to analyze the feasibility of adjuvant capecitabine therapy using a tailored-dose escalation strategy in elderly patients with colon cancer (CC).MethodsCC patients (≥70 years of age) who received adjuvant capecitabine were enrolled. The starting dosage of capecitabine was 2000 mg/m²/day (days 1–14, every 3 weeks). On the second cycle, the dosage was escalated to 2500 mg/m²/day if the patient tolerated the first cycle. Dose intensity (DI), toxicity, and the change in quality of life (QoL) were evaluated.ResultsOf 82 patients enrolled, 67 completed eight cycles. Dose escalation to 2500 mg/m²/day was possible in 56 patients, and this dosage was maintained in 24 patients until the completion of chemotherapy (eight cycles). Forty-one patients completed therapy with a DI ≥ 1333 mg/m²/day [relative dose intensity (RDI) ≥ 80%]. Toxic effects were tolerable and the QoL was not compromised during treatment. Creatinine clearance <50 ml/min and Charlson-Age comorbidity index ≥8 were related to a reduced capecitabine dosage (RDI < 80%).ConclusionsA tailored-dose escalation strategy was feasible in elderly CC patients receiving adjuvant capecitabine chemotherapy. Decreased renal function and an increased number of comorbidities were independently predictive of reduced administration of the capecitabine dose.     

Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum

Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FU) by 3 sequential steps of enzyme reactions. We investigated the possibility of using capecitabine to prevent metastasis with a metastasis model of gastrointestinal cancer developed by the intrarectal injection of green fluorescent protein (GFP)-expressing colon cancer HT-29 cells (HT-29-GFP) into nude mice. Lung and lymph node metastasis in the HT-29-GFP rectal xenograft was assessed through both observation of GFP fluorescence and quantification of metastasis by amplification of a cancer-related human DNA by TaqMan PCR. Furthermore, for each organ, we examined mRNA levels of cancer-specific thymidine phosphorylase (dThdPase), which is an essential enzyme for capecitabine activation, by the quantitative RT-PCR method. Capecitabine inhibited the HT-29-GFP xenograft growth by 60.8% and 43.8% in the subcutaneous and rectal xenograft models, respectively. Furthermore, it inhibited both lung and lymph node metastasis by 99.9%. dThdPase expression in the tumor cells of both the rectal xenograft and metastatic lung tumor cells was upregulated by 10.0- and 24.3-fold that in the HT-29-GFP cells in vitro, respectively. These results indicated that capecitabine might effectively inhibit or suppress metastasis via upregulation of dThdPase expression. Capecitabine administration might be highly expected to reduce metastasis and improve survival of patients with gastrointestinal cancers.     

Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma

BACKGROUND: The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma. METHODS: The authors performed a retrospective analysis of all patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or gallbladder carcinoma (GBC) who were ever treated with oral capecitabine. The medical records of 116 patients with hepatobiliary carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between July 1998 and March 1999 were reviewed. RESULTS: A total of 63 patients were treated with capecitabine (37 with HCC, 18 with CCA, 8 with GBC). Capecitabine 1000 mg/m(2) was administered twice daily for 14 days. Treatment was repeated every 21 days. Each patient received 1-15 treatment cycles. Nine patients (14%)-11% of patients with HCC, 6% of patients with CCA, and 50% of patients with GBC-had either a complete response (CR) or a partial response. A CR was radiologically confirmed in one patient with HCC and in two patients with GBC. The median survival times were 10.1 months (95% confidence interval [CI], 4.5-15.7 months) for patients with HCC, 8.1 months (95% CI, 7.4-8.9 months) for patients with CCA, and 9.9 months (95% CI, 4.4-15.4 months) for patients with GBC. The most common toxicity was hand-foot syndrome (37%). Grade 3 thrombocytopenia occurred in 8% of patients with HCC. No other significant toxicities were observed. For all patients, response to treatment was positively correlated with survival and decline in tumor markers. CONCLUSIONS: Capecitabine was found to be safe for patients with hepatobiliary carcinoma, including those with cirrhosis. The antitumor activity of single-agent capecitabine was most pronounced in patients with GBC, was modest in patients with HCC, and was poor in patients with CCA.     

多西紫杉醇联合卡培他滨治疗晚期乳腺癌22例的临床观察

背景与目的：对于复发转移性乳腺癌，卡培他滨和紫杉醇类药物均有确切肯定的疗效，由于紫杉醇类药物能增强肿瘤组织的TP活性，因而与卡培他滨有协同作用。本研究观察及评价多西紫杉醇联合卡培他滨治疗复发转移性乳腺痈的疗效和不良反应。方法：22例晚期乳腺癌患者均给予多西紫杉醇75mg／m^2，第1天；卡培他滨口服每日2次，餐后服用，1000mg／m^2／次，连续服用14天，治疗周期为21天，至少治疗2个周期。结果：本组完全缓解（CR）3例，部分缓解（PR）12例，稳定（SD）6例，疾病进展（PD）1例，总有效率68．2％，中位TTP6．5个月。不同转移部位或器官的有效率分别为：胸壁85．7％（6／7）；淋巴结80．0％（8／10）；肺脏75．0％（6／8）；骨骼40．0％（2／5）；肝脏30．0％（3／10）。Ⅰ／Ⅱ级不良反应为皮肤色素沉着16例，手足综合征14例，恶心呕吐12例，腹泻10例，白细胞下降16例。Ⅲ／Ⅳ级不良反应白细胞下降3例，恶心呕吐1例，贫血1例。结论：多西紫杉醇联合卡培他滨治疗晚期乳腺癌疗效肯定，患者耐受性良好。     

卡培他滨维持治疗晚期乳腺癌的临床观察

背景与目的：卡培他滨是晚期乳腺癌一线治疗方案用药,但在晚期乳腺癌的维持治疗中的研究较少。本文旨在探讨卡培他滨维持治疗晚期乳腺癌的疗效及不良反应。方法：将一线化疗后处于完全缓解(complete response,CR)、部分缓解(partial response,PR)或疾病稳定(stable disease,SD)的62例患者分为2组,卡培他滨治疗组(31例)患者予以单药口服卡培他滨维持治疗,对照组(31例)患者予以定期随访观察。每2个化疗周期后评价疗效。结果：卡培他滨治疗组中位疾病进展时间(time to progression,TTP)为12(2～24)个月,明显高于对照组的7(1～18)个月,且2组差异有统计学意义(P<0.05)。在亚组分析中,未绝经组、激素受体阳性组、HER-2阳性组、有内脏转移组、有肺转移组及既往未接受过卡培他滨化疗组的患者中,卡培他滨治疗组患者的TTP均显著高于对照组患者。卡培他滨治疗组总有效率(CR+PR)为19.4%(6/31),肿瘤控制率(CR+PR+SD)为74.2%(23/31)。主要不良反应为手足综合征及血液学不良反应,其次为胃肠道不良反应,但均可以耐受。卡培他滨治疗组的生活质量评分较对照组明显提高。结论：卡培他滨用于晚期乳腺癌一线治疗后的维持治疗可以延缓疾病进展,提高生活质量。     

Oral cancer treatment: developments in chemotherapy and beyond

Oncology is one of the few areas of medicine where most patients are treated intravenously rather than receiving oral drugs. Recently, several oral anti-cancer drugs have been approved and there are many more in development. Oral chemotherapy is attractive because of its convenience and ease of administration, particularly in the palliative setting. With an increasing number of oral agents emerging, we can expect to see a rapid rise in the use of oral chemotherapy in years to come. This article reviews recent developments in oral chemotherapy, both of traditional cytotoxics and novel, targeted agents, from the viewpoint of patients, physicians, drug developers and health-care providers.