转移性结直肠癌患者不同化疗方案的成本效益分析

目的了解治疗转移性结直肠癌的主要化疗方案FOLFIRI（伊立替康、亚叶酸钙和氟尿嘧啶）和FOLFOX6（奥沙利铂、亚叶酸钙和氟尿嘧啶）的成本效益。方法以V308临床研究为基础，根据复旦大学附属中山医院的2007年第一季度的收费标准，分别计算FOLFIRI和FOLFOX6两种化疗方案序贯治疗的最小成本，并进行成本效益分析。结果在转移性结直肠癌患者的序贯治疗中，如果一线采用FOLFIRI方案，二线采用FOLFOX6方案治疗。与相反治疗顺序相比，每例患者的平均最小成本分别为206365．78元和170468．89元，每例患者总生存期增加1个月，前者较后者多花费39885．44元人民币。结论FOLFIRI和FOLFOX6方案可使转移性结直肠癌患者的总生存期延长，但治疗成本相当昂贵，FOLFOX6方案更具成本效益比。     

卡培他滨联合奥沙利铂治疗晚期结直肠癌的近远期效果观察

为观察卡培他滨联合奥沙利铂治疗晚期结直肠癌的近远期效果,将晚期结直肠癌患者60例随机分为对照组和观察组,每组30例。对照组患者采用卡培他滨联合奈达铂化疗方案治疗,观察组患者采用卡培他滨联合奥沙利铂(XELOX)化疗方案治疗,比较2组患者近期临床疗效、远期生存率以及观察治疗过程中2组患者出现的不良反应情况。结果显示,观察组患者的近期临床总有效率明显高于对照组(P <0.05)。随访1年,2组患者的远期生存率比较差异无统计学意义(P>0.05);随访2年观察组患者的远期生存率高于对照组(P <0.05),随访3年观察组患者的远期生存率明显高于对照组(P <0.05)。2组患者不良反应发生率比较差异无统计学意义(P>0.05)。结果表明,采用XELOX化疗方案治疗晚期结直肠癌患者可明显提高近期临床疗效和远期生存率,且药物的安全性良好,值得临床推广应用。     

应用氟尿嘧啶肠腔化疗辅助结,直肠癌根治术的远期效果

本文报告８２例大肠癌随机分为两组：试验组４５例，除施行根治术外。辅加肠腔５－ＦＵ化疗和术后第１、２天５－ＦＵ全身化疗；对照组３７例，单纯施行根治术。Ｄｕｋｅｓ’Ｃ期病人试验组３年、５年和８年生存率分别为７５．５％、６５．４％、和２８．５％，而对照组仅５８．３％、２５．０％和５．６％，两者差异有显著性（Ｐ＜０．０５）。另外，试验组肝转移比对照组少。故此法是提高结、直肠癌根治术疗效和防止肝转移的重要措施，值得推广应用。     

结直肠癌化疗药物和方案的选择

恶性肿瘤是当前疾病死亡的主要原因之一。结直肠癌(CRC)又为发病和死亡均占重要位置的恶性肿瘤。IARC的资料显示：全世界恶性肿瘤的发病例数在1975年为587万，至1990年上升为807万，上升37．4％。到2000年，已达1006万，又上升了24．7％。如以2000年与1975年相比．则上升了71．4％。2000年全球癌症死亡人数为620万，共有现     

结直肠癌术后顺铂和5-氟尿嘧啶化疗及枢复宁对胃肠动力的影响

14例结直肠癌术后化疗病人进行胃肠动力采用 PC Polygraf HR 台式高分辨八导消化道动力监测系统进行测压;第一天为对照期,第二天为化疗期,方案为顺铂40mg 和5-FU 500mg;第三天为枢复宁期,继续化疗药物,化疗前5min 静推枢复宁8mg。结果显示对照期 MMC 个数为9.14±2.54个/人,化疗期增至13.14±3.96个/人(P<0.01)。枢复宁期MMC 数为13.07±3.60个/人。MMC 周期对照期为170±50min,化疗期期缩短至122±47min(P<0.05)。枢复宁期为124±65min。MMC 移行速度对照期为0.114±0.028cm/sec,化疗期加快至0.161±0.049cm/sec,枢复宁期 MMC 的移行速度平均为0.13±0.017cm/sec。MMCⅢ相收缩波数对照期为453±109个/人。化疗期增加至664±196个/人(P<0.01)。枢复宁期 MMCⅢ相收缩波数为646±209个/人。MMCⅢ相收缩波幅植对照期为4.09±0.99kPa,化疗期为4.13±1.13kPa(P<0.05)。枢复宁期为3.92±1.19kPa。应用化疗药物后14例病人中9例发生呕吐,发生呕吐的时间为280±28min。应用枢复宁后,无病人再发生呕吐(P<0.05),但不增强胃肠道平滑肌的收缩强度。枢复宁可抑制化疗药物引起的呕吐,化疗药物引起胃肠动力加快和呕吐属于两不同的机制,两者间无因果关系。     

卡培他滨为主的联合方案治疗晚期转移性乳腺癌

目的探讨以卡培他滨(希罗达)为主的联合化疗方案治疗转移性乳腺癌的临床效果及毒副反应。方法 42例转移性乳腺癌患者中,23例为既往使用蒽环类治疗失败,给予希罗达联合诺维本治疗(诺维本25 mg/m2,化疗周期的第1天及第8天各静脉滴注1次;希罗达2 000 mg/m2,口服,2次/d,服用2周,每3周为1个周期);1 9例既往未曾采用蒽环类治疗,给予希罗达联合吡柔比星(吡柔比星35 mg/m2,化疗周期的第1天及第8天各静脉滴注1次;口服希罗达,剂量、用法疗程同上)。所有患者至少接受化疗6周期后方可评价疗效。结果希罗达联合诺维本组完全缓解(CR)5例,部分缓解(PR)12例,稳定(SD)4例,进展(PD)2例;有效率为73.91%(17/23);中位疾病进展时间(TTP)为8.4个月,中位生存期(MST)为18.1个月。希罗达联合吡柔比星组CR 5例,PR 7例,SD2例,PD 5例;有效率为6 3.1 6%(1 2/1 9);TTP为个7.8个月,MST为17.5个月。两组之间化疗有效率无明显差异(P>0.05)。两组主要毒副反应为白细胞减少,其中III～IV度占52.4%;手足综合征II～III级者占1 9...     

结直肠癌患者口服卡培他滨化疗不同时期的服药依从性及其影响因素分析

目的:探讨结直肠癌患者口服卡培他滨化疗不同时期的服药依从性及其影响因素。方法:选取2021年1～12月于我院就诊并接受卡培他滨口服化疗的120例结直肠癌患者为观察对象,患者化疗初期(第1个周期)、中期(第4个周期)、末期(第8个周期)均接受Morisky服药依从性问卷、服药信念特异性问卷、癌症生活质量问卷调查,分析化疗不同时期患者的服药依从性及其影响因素。结果:本组共20例患者放弃服用药物,其中16例于化疗前3个周期内放弃用药。坚持用药的患者化疗初期、中期、末期服药依从性评分分别为(7.41±1.02)分、(6.94±1.09)分和(6.81±1.27)分,各期患者服药依从性评分比较差异有统计学意义,P<0.05。影响化疗用药初期服药依从性的因素主要有食欲丧失、服药信念和文化程度,影响用药中期服药依从性的因素主要有疲乏、造口与否,影响用药末期服药依从性的因素主要为居住地。结论:结直肠癌口服卡培他滨化疗前3个周期最易放弃服药,能坚持用药的患者服药依从性较好,但化疗不同时期患者用药依从性受不同因素影响,医护人员应有针对性予以护理干预。     

伊立替康联合氟尿嘧啶/亚叶酸钙治疗转移性结直肠癌

目的观察伊立替康联合亚叶酸钙及氟尿嘧啶方案治疗FOLFOX4方案失败的晚期结直肠癌的临床疗效及毒副反应。方法用CPT-11联合5-FU/CF方案治疗晚期结直肠癌患者28例,采用2周方案化疗,至少2个周期,即CPT-11180mg/m2静脉滴注,第1天;四氢叶酸200mg/m2静脉滴注,第1、2天;5-FU400mg/m2静脉推注,第1、2天;5-FU600mg/m2静脉滴注22h,第1、2天。按照WHO实体瘤近期客观疗效评定标准进行评价。结果全组28例患者均可评价疗效及不良反应。其中完全缓解0例,部分缓解10例,稳定9例,进展9例,有效率为35.7%。中位肿瘤进展时间TTP6.5个月,中位生存时间MST为12.5个月。不良反应主要是骨髓抑制,恶心、呕吐,脱发及延迟性腹泻。结论伊立替康联合5-FU/CF为二线治疗晚期结直肠癌安全有效的方案。     

伊立替康联合氟尿嘧啶一线治疗老年／年轻转移性结直肠癌患者：一组2691例的随机对照分析

目的目前还不能确定老年转移眭结直肠癌患者接受联合伊立替康一线化疗的获益是否与年轻患者一致。方法通过对比研究599例老年患者（≥70岁）和2092例年轻患者（〈70岁）的结直肠癌患者接受Ⅲ期临床试验的原始资料,总结分析氟尿嘧啶（FU）及亚叶酸（FA）和伊立替康的联合疗法及单一疗法在一线化疗方案中的安全性和有效性。结果老年患者和年轻患者中,以伊立替康为基础的联合化疗反应率较FU／FA高（分别为46．6％ vs 29．0％,P〈0．01;50．5％vs30.3％,P〈0．01）。伊立替康／FU／FA方案的无进展生存期在年轻患者[风险率（HR）=0．77,95％CI=0．70～0．85,P〈0．01]和老年（HR=0．75,95％CI=0．61～0．90,P〈0．01）患者中均较好。年轻患者（HR=0.83,95％CI=0．75～0．92,P〈0.01）联合化疗的总生存率较高,老年患者（HR=0.87,95％CI=0.72～1．05,P〈0.15）也具有同样的趋势。回归分析显示：年龄在治疗方案之间不具显著相关性。单一用药与联合用药对老年和年轻患者肝脏的毒性不同得到证明。以年龄作为可变量的分析,证明年龄（不包括70岁）在治疗中与肝脏毒性和呕吐无显著相关。结论在Ⅲ期试验中,伊立替康化疗对大于70岁的老年患者和年轻患者疗效相当,其对两者的毒性相似。     

结直肠癌术后顺铂和5-氟尿嘧啶化疗及枢复宁对胃肠动力的影响

14例结直肠癌术后化疗病人进行胃肠动力采用PC Polygraf HR台式高分辨八导消化道动力监测系统进行测压；第一天为对照期，第二天为化疗期，方案为顺铂40mg如和5-FU 500mg；第三天为枢复宁期，继续化疗药物，化疗前5min静推枢复宁8mg。结果 显示对照期MMC个数为9．14±2．54个从，化疗期增至13．14±3．96个从(P<0.01)。枢复宁期MMC数为13．07±360个／人。MMC周期对照期为170±50min．化疗期期缩短至122±47min(P<0．05)。枢复宁期为124±65min。MMC移行速度对照期为0．114±0.028cm／sec，化疗期加快至0.161±0．049cm／sec，枢复宁期MMC的移行速度平均为0．13±0.017cm／sec。MMCⅢ相收缩波数对照期为453±109个/人。化疗期增加至664±196个从(P<0.01)。枢复宁期MMCⅢ相收缩渡数为646±209个／人。MMCⅢ相收缩波幅植对照期为409±0．99kPa，化疗期为4．13±1．13kPa(P<0．05)。枢复宁期为3．92±1．19kPa。应用化疗药物后14例病人中9例发生呕吐，发生呕吐的时间为280±28min。应用枢复宁后，无病人再发生呕吐(P<0.05)，但不增强胃肠道平滑肌的收缩强度。枢复宁可抑制化疗药物引起的呕吐，化疗药物引起胃肠动力加快和呕吐属于两不同的机制，两间无因果关系。     

Method of Presenting Oncology Treatment Outcomes Influences Patient Treatment Decision-Making in Metastatic Colorectal Cancer

Background The methods used to communicate relevant outcomes in oncology to patients will likely influence treatment decisions. The purpose of this study was to examine the influence of three different methods of describing the efficacy of therapy on treatment decisions regarding management of metastatic colorectal cancer. Methods Participants reviewed a clinical scenario and randomly received one of three ways of describing efficacy of chemotherapy in metastatic colorectal cancer: (1) relative risk reduction, (2) tumor response rate, and (3) median overall survival. They received the same clinical scenario but were presented four treatment options: (1) observation and supportive care, (2) chemotherapy, (3) surgery, and (4) surgery and chemotherapy and the accompanying median overall survival estimate. Results Participants included 102 preclinical medical students. In the first scenario, 85% chose chemotherapy in the relative risk reduction group, as did 88% of the tumor response rate group, but significantly fewer participants did so in the median overall survival group (35%; P < .001). In the second scenario, there was a significant difference in treatment preferences, with 4% of participants choosing observation/supportive care. None chose chemotherapy only, 19% chose surgery only, and 77% chose surgery plus chemotherapy (P < .001). Conclusions This study demonstrated that different methods of describing oncology treatment outcomes associated with therapy for metastatic colorectal cancer to the liver can have a dramatic effect on patient treatment decisions.     

淋巴结转移率对结直肠癌患者预后的影响

为探讨淋巴结转移率（rN）对结直肠癌患者预后的影响,回顾分析362例结直肠癌患者的临床病理资料和随访情况,分析rN与结直肠癌患者预后的关系。结果显示,患者3年、5年生存率与rN分期有关,P〈O．05。结果表明,rN分期可帮助评估结直肠癌患者的预后。     

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

Background We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown. Methods Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m² 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen). Results Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively. Conclusions HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.     

转移性肝癌的外科治疗(附208例报告)

目的　探讨转移性肝癌手术治疗效果。方法　回顾性分析我院近7 年来收治的208 例转移性肝癌患者资料,根据治疗方式不同,将其分为切除性手术组(116 例)与非切除性手术组(92 例),比较两组的治疗效果。结果　全组手术无死亡,术后1、3、5年生存率分别为56.3%、23.1%和13.0%。切除性手术组患者1、3、5 年总生存率分别为74.1%、39.7%和23.3%,非切除性手术组患者1、3、5年生存率分别为33.7%、2.2%和0,前者的治疗效果明显好于后者(P<0.05)。结论　切除性手术是转移性肝癌有效的治疗方法,能耐受切除者应力争切除治疗。     

The Prognostic Importance of Metastatic Site in Men with Metastatic Castration-resistant Prostate Cancer

The presence of visceral metastases is adversely prognostic in men with metastatic castration-resistant prostate cancer (mCRPC), but the prognostic impact of the site of visceral metastasis is unclear. Men with mCRPC in the TAX 327 phase 3 trial receiving docetaxel or mitoxantrone every 3 wk or weekly docetaxel, each with prednisone, were analyzed retrospectively to study the impact of the site of visceral metastasis on overall survival (OS). Patients were assessed for OS by site of metastases: liver with or without other sites, lung with or without bone or lymph nodes, bone plus lymph nodes, bone only, and lymph nodes only. Cox proportional hazards regression, adjusted for treatment and stratification factors, was performed. Men with liver metastases with or without other metastases had shorter median OS (10.0 mo; 95% confidence interval [CI], 5.4–11.5) than men with lung metastases with or without bone or nodal metastases (median OS: 14.4 mo; 95% CI, 11.5–22.4). Men with lymph node-only disease had the best median OS (26.7 mo; 95% CI, 22.3–34.2), followed by men with bone-only metastases (median OS: 19.0 mo; 95% CI, 18.2–20.7) and bone-plus-node disease (median OS: 15.7 mo; 95% CI, 14.4–17.2). Thus, pattern of spread including site of visceral metastasis confers a differential prognostic impact. These data require validation and may inform trial design and therapy.     

Pilot Study of Low-Dose,Divided Maximum Tolerated Dose of CPT-11 in 21 Consecutive Patients with Metastatic Colorectal or Gastric Cancer

Purpose We devised a new treatment regimen, delivering a frequent low dose of CPT-11, calculated by dividing the maximum tolerated dose (MTD) to reduce its toxicity without impairing its efficacy.Methods CPI-11, 25mg/m², determined by dividing the MTD dose per month by 12, was given on days 1, 2, and 3 of every week, to 21 consecutive patients; 12 with metastatic colon cancer and 9 with metastatic gastric cancers.Results The total delivered dose of CPI-11 per patient was more than 1000mg in 17 (80.1%) of the 21 patients. Grade 3 marrow depression developed in 3 (14.3%) patients, and although nausea, vomiting, alopecia, and diarrhea developed in some patients, these side effects were all categorized as grade 2 or milder. The antitumor effect was evaluated in 18 patients with measurable lesions, who had received CPI-11 according to our regimen for at least 3 weeks. Of these 18 patients, 10, 7, and 1, respectively, had a found to have partial response, no change, or progression of disease, demonstrating a 55.6% efficacy rate [colon 6/10 (60.0%) and stomach 4/8 (50.0%)]. Moreover, time to progression (TTP) was greater than 90 days in 12 (75.0%) of these 18 patients.Conclusion These results show that our low-dose, divided MTD of CPI-11 regimen is a promising method of reducing toxicity and strengthening the antitumor effect, justifying further large-scale comparative clinical studies to verify this potential.     

Isolated Hepatic Perfusion for the Treatment of Patients With Colorectal Cancer Liver Metastases After Irinotecan-Based Therapy

Background Irinotecan given with 5-fluorouracil and leucovorin is currently used as first-line therapy for patients with metastatic colorectal cancer (CRC). However, the response duration is <1 year, and second-line systemic chemotherapy has limited efficacy. We analyzed the efficacy of isolated hepatic perfusion (IHP) for patients with progressive CRC liver metastases after irinotecan.Methods Between March 1993 and February 2003, 124 patients with CRC liver metastases underwent IHP on institutional review board–approved protocols. The overall treatment mortality was 4% (5 of 124). Twenty-five patients (10 women and 15 men; mean age, 53 years) were identified who had progressive liver metastases by carcinoembryonic antigen, imaging studies, or both after irinotecan. A 1-hour hyperthermic IHP (mean hepatic temperature, 40.0°C) with melphalan 1.5 mg/kg (mean total dose, 100 mg) was administered via laparotomy. Perfusion with an oxygenated extracorporeal circuit was established with inflow via a cannula in the gastroduodenal artery and common hepatic artery inflow occlusion. Outflow was via a cannula in an isolated segment of the inferior vena cava. During IHP, portal and inferior vena caval flow were shunted to the axillary vein. Patients were assessed for radiographical response, recurrence pattern, and survival.Results The mean number of prior irinotecan cycles in 25 patients was 6 (range, 2–14), and it was given primarily as second-line therapy. The median number of liver metastases before IHP was 10 (range, 1–50), and the median percentage of hepatic replacement by tumor was 25%. The mean operative time was 9 hours (range, 6–12 hours), and the median hospital stay was 11 days (range, 8–76 days). There was 1 complete response and there were 14 partial responses in 25 patients (60%), with a median duration of 12 months (range, 5–35 months). Disease progressed systemically in 13 of 25 patients at a median of 5 months (range, 3–16 months). The median overall survival was 12 months (range, 1–47 months), and the 2-year survival was 28%.Conclusions For patients with progressive CRC liver metastases after irinotecan, IHP has good efficacy in terms of response rate and duration. Continued evaluation of IHP with melphalan as second-line therapy in this clinical setting is justified.     

女性大肠癌卵巢转移的高危因素及治疗探讨

探讨女性大肠癌卵巢转移的高危因素。方法:对我院1990年4月至1996年4月经手术及病理证实的77例女性大肠癌进行临床及病理因素的单因素。多因素分析。结果:具有年龄≤50岁、肿瘤细胞分化程度低及肿瘤侵犯浆膜层三个因素者卵巢转移率明显增高。结论:上述三个因素是女性大肠癌卵巢转移的高危因素。建议女性大肠癌手术前常规作妇科及盆腔B超检查,术中认真探查双侧卵巢,高度重视卵巢的囊性改变。对未切除卵巢者,术后应密切随访卵巢情况。     

A Prospective Randomized Trial Comparing Intravenous 5- Fluorouracil and Oral Doxifluridine As Postoperative Adjuvant Treatment for Advanced Rectal Cancer

Background: Postoperative adjuvant chemoradiation treatment after curative resection for rectal cancer was needed to reduce recurrence and improve a survival rate. Intravenous 5-fluorouracil (5-FU) and leucovorin has been a mainstay of chemotherapy, but oral 5-FU derivatives have been shown a comparable antitumor activity. Intravenous 5-FU and oral doxifluridine were compared with respect to therapeutic efficacy, drug toxicity, and quality of life.Methods: A total of 166 patients were randomized to receive intravenous 5-FU (450 mg/m²/day) or oral doxifluridine (900 mg/m²/day) in combination with leucovorin (20 mg/m²/day) for depth of invasion, nodal status, metastasis (TNM) stage II and III patients between October 1997 and February 1999. Consecutive daily intravenous infusion for 5 days per every month for a total of 12 cycles (IV arm, n = 74) and oral doxifluridine daily for 3 weeks and 1 week rest for a total of 12 cycles (oral arm, n = 92). Drug toxicity and quality of life were observed. Quality of life was scored according to 22 daily activity items (good, 71; fair, < 70; poor, < 52).Results: There was no difference of sex between two groups (IV arm: male/female = 45/29, oral arm: male/female = 59/33). The mean age was 52.3 vs. 59.5, respectively. There was also no difference of TNM stage distribution and type of operation between groups (P = .05). Mean numbers of chemotherapy cycles were 6.5 ± 3.7 (IV arm) vs. 7.2 ± 4.3 (oral arm), respectively. The rate of recurrence was 9/74 (12.1%) in the IV arm and 6/92 (6.5%) in the oral arm, respectively (P = .937). Local recurrence was 2/74 (stage III; 2.7%) in the IV arm and 1/92 (stage II;1.1%) in the oral arm, respectively. Systemic recurrence was 7/74 (stage III; 9.4%) in the IV arm and 5/92 (stage III; 5.4%) in the oral arm, respectively. The most common site of systemic recurrence was the liver. Toxicity profile was as follows: leukopenia (30/74 vs. 17/92) and alopecia (21/74 vs. 13/92) were statistically more common in the IV arm. Diarrhea was more common in the oral arm. Poor quality of life score between two groups was observed at 1 month (23.9% vs. 13%) and 2 months (15.8% vs. 3.7%) after chemotherapy. Good quality of life score was observed at 1 month (19.5% vs. 49%) and 2 months (47% vs. 72%), respectively (P < .05).Conclusions: Oral doxifluridine with leucovorin shows a comparable therapeutic efficacy to intravenous 5-FU regimen with high quality of life as postoperative adjuvant therapy. The oral regimen also can be safely given with appropriate toxicity and tolerability.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.