口服与注射长春瑞滨联合卡培他滨治疗蒽环类，紫杉类耐药性晚期乳腺癌的比较研究

目的 探讨口服长春瑞滨联合卡培他滨治疗葸环类、紫杉类耐药的转移性乳腺癌的疗效及不良反应。方法 80例确诊葸环类、紫杉类耐药的转移性乳腺癌患者随机分为两组。口服长春瑞滨联合希罗达组（试验组）：40例患者口服江苏豪森酒石酸长春瑞滨软胶囊45．50mg／（m^2-d），第1、8、15天服用，口服卡培他滨1650mg／（m^2·d），连服1—14d，每3周为1个周期，连用4个周期。注射长春瑞滨联合希罗达组（对照组）：40例患者，长春瑞滨（江苏豪森）25mg／（m^2·d）第1、8天静脉滴注，口服卡培他滨1650mg／（m^2·d），连服1-14d，每3周为1个周期，连用4个周期。治疗结束2周后评价疗效。结果 入组患者80例均可评价疗效，试验组有效率为42．5％，1年生存率为45．0％，中位进展时间4．7月，中位生存时间11．0月；对照组有效率为37．5％，1年生存率为42．5％，中位进展时间4．6月，中位生存时间10．6月；两组比较差异无统计学意义（P〉0．05）。在毒副反应方面，Ⅲ／IV便秘、局部静脉炎、HB下降、WBC下降、ANC下降、总Ⅲ／IV反应率两组比较。差异均有统计学意义（P〈0．05）。结论 口服长春瑞滨联合卡培他滨治疗葸环类、紫杉类耐药的转移性乳腺癌与静脉剂型疗效一致，并且在毒副反应上，口服长春瑞滨明显较静脉剂型轻，并且应用方便。     

草酸铂联合卡培他滨治疗晚期胃癌的近期疗效分析

目的：探讨草酸铂联合卡培他滨治疗晚期胃癌的近期疗效。方法：对32例晚期胃癌采用草酸铂联合卡培他滨方案治疗共76周期。结果：CR6例，PR16例，NC8例和PD2例，总有效率(CR PR)为68．75％(22／32)。中位缓解期8个月，中位生存期12个月，1年生存率为55％；临床受益者共30例(93．75％)。不良反应可耐受，经积极对症治疗后均见好转，无相关死亡出现。无患者因为不良反应中止治疗。结论：草酸铂加卡培他滨方案而组成的OX方案治疗晚期胃癌疗效较好，毒性反应能够耐受，可作为经济状况好的患者的一线方案在更多的病人中应用，以进一步探讨其疗效。     

卡培他滨联合肝动脉栓塞化疗治疗原发性肝癌

目的 :探讨卡培他滨联合经肝动脉栓塞化疗 (TACE)治疗晚期肝癌的有效性。方法 :6 2例不能手术切除的晚期肝癌患者 (TNM分期Ⅱ～Ⅳ )随机分成两组 :①单纯TACE组 30例 ;②卡培他滨联合TACE组 32例 ,在TACE治疗后第 2天 ,口服给药 14天。全部患者随访两年。比较两组患者的中位生存时间 ,死亡患者平均生存时间、一年生存率、二期手术切除率。结果 :卡培他滨联合TACE治疗组患者的中位生存时间为 14 .5个月 ,一年生存率为 75 .0 % ,二期手术切除率 2 5 .0 % ;而单纯TACE组患者的中位生存时间为 6个月 ,一年生存率为 39.3% ,二期手术切除率 6 .7% ,两组比较有显著差异 (P <0 .0 5 )。结论 :卡培他滨联合TACE治疗晚期原发性肝癌患者的疗效优于单纯TACE。     

Capecitabine and vinorelbine in elderly patients (> or =65 years) with metastatic breast cancer: a phase I trial (SAKK 25/99).

BACKGROUND: Few chemotherapy regimens are suitable for the treatment of elderly patients with advanced breast cancer. With the aim of finding a regimen with a low burden of subjective non-overlapping toxic effects, vinorelbine and capecitabine were chosen to be investigated in a phase I dose-finding study. PATIENTS AND METHODS: Thirty-six patients with advanced breast cancer were stratified for the presence of bone and non-bone involvement and treated at four dose levels from capecitabine 800 mg/m2 orally days 1-14 and vinorelbine 20 mg/m2 intravenously days 1 and 8, to capecitabine 1250 mg/m2 orally days 1-14 and vinorelbine 25 mg/m2 intravenously days 1 and 8, for a maximum of six cycles. None of the patients had received prior chemotherapy for metastatic/advanced disease. Fifty-three per cent of patients with bone metastases and 67% of patients without bone metastases had visceral disease. The median age was 70 years for the 15 with bone involvement patients and 73 years for the 21 without bone involvement patients. RESULTS: Twenty-eight patients were fully evaluable for hematological dose-limiting toxicity (DLT), and all patients for other DLTs and for antitumor activity. One DLT with grade 3 venous thrombosis at dose level 2 and two dose-limiting neutropenia events at level 3 occurred in patients without bone involvement. Two dose-limiting neutropenia events were observed at dose level 2 for patients with bone involvement. Thus, the recommended dose was defined at level 1 (capecitabine 1000 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8) for patients with bone involvement. For patients without bone involvement, the recommended dose was at level 2 (capecitabine 1250 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8). For patients without bone involvement the overall response rate was 48% and the time to progression (TTP) was 4.5 months [95% confidence interval (CI) 3.3-6.9]. For patients with bone involvement the overall response rate was 53% and TTP was 5.3 months (95% CI 2.7-7.8). CONCLUSIONS: This regimen of capecitabine and vinorelbine is well tolerated and effective in elderly patients with metastatic breast cancer. Toxicity was mainly hematological and was observed at a lower dose in patients with bone involvement. A phase II study with the two different dose levels for elderly patients with and without bone involvement is currently being conducted.     

Lower dose capecitabine has a more favorable therapeutic index in metastatic breast cancer: retrospective analysis of patients treated at M. D. Anderson Cancer Center and a review of capecitabine toxicity in the literature.

BACKGROUND: Capecitabine is active against anthracycline- and taxane-pretreated metastatic breast cancer. Post-marketing use of capecitabine at the FDA-approved dose (2500 mg/m2/day) leads to unacceptable toxicity in many patients. Dose reductions anecdotally improve tolerability without compromising efficacy. This retrospective analysis was designed to verify these anecdotal reports. Patients and methods: We retrospectively reviewed the records of 141 consecutive patients with metastatic breast cancer identified from pharmacy records as receiving capecitabine outside of a clinical trial between May 1998 and February 1999. Responses were defined as clinical improvement (ID), stabilization of disease (SD) for 6 weeks or longer, or progression (PD). Patients were grouped according to the starting dose level of capecitabine: A=2500+/-5% (dose range 2385-2560) mg/m2/day; B=2250+/-5% (range 2130-2350) mg/m2/day; C < or = 2000+5% (range 1000-2100) mg/m2/day. We also reviewed the safety profile of capecitabine at these doses and performed a safety review of capecitabine in phase II and III metastatic breast and colorectal cancer trials. RESULTS: Clinical data were available for 113 patients (105 for response, 106 for toxicity). The median age was 52.5 years and the mean number of prior metastatic chemotherapy regimens was 2 (range 0-7). The mean capecitabine starting dose was 2220 mg/m2/day and the median number of cycles administered was 4 (range 1-19). The mean tolerated dose was 2040 mg/m2/day (range 960-2670). Grade 3/4 toxic effects at dose levels A, B and C, respectively, included palmar-plantar erythrodysesthesia (33%, 63%, 20%), diarrhea (13%, 12%, 3%), stomatitis (8%, 0%, 3%), and nausea/vomiting (4%, 6%, 5%). Forty per cent of all patients required capecitabine dose reductions; fewer patients treated with 2000 mg/m2/day required dose modification (28%). Five per cent of the patients required discontinuation of capecitabine owing to toxicity. Patients started at the lowest doses of capecitabine did not have poorer response rates or shorter time to progression. CONCLUSIONS: This retrospective analysis supports a starting dose of 2000 mg/m2/day because of its superior therapeutic index; however, patients may still have toxic effects and individualization of dosing is necessary. A phase III, multicenter, randomized study to establish the safety and efficacy of different doses of capecitabine is urgently needed.     

卡培他宾治疗晚期肝癌临床观察

目的 探讨卡培他宾在晚期肝癌临床治疗中的疗效。方法 将我科收住的34例肝癌病人随机分为两组：①治疗组：希罗达2000mg／m^2，分2次／d 口服、连用14d，休息7d，为一周期，至少用药二周期以上；②对照组：单纯支持治疗，至少6wk。治疗前后查肝肾功能，血常规，AFP，ECG，CT或MRI、B超等。疗效和不良反应按WHO疗效及不良反应评价标准评价，统计分析方法采用x^2检验，P〈0．05为有统计学意义。结果 治疗组：CR无病例，PR2例，SD10例，PD6例；总有效例数2例，总有效率为11．8％，稳定率58．8％。12例AFP增高中5例下降，下降率为41．7％。生存期最短的为3mo，最长的7mo，中位生存期为5．3mo。希罗达最少为2周期，最多6周期，共40周期。对照组：CR无病例，PR无病例，SD2例，PD15例；总有效率为零，稳定率11．8％。11例AFP增高病人中无AFP下降。生存期最短的为1．5mo，最长的4mo，中位生存期为2．3mo。采用x^2检验，P〈0．05，两组有显著的统计学差异。不良反应，治疗组3例恶心、呕吐，3例中性粒细胞减少，3例出现腹泻，皮肤红肿、脱屑等手足综合征，这些副反应均在1乏级。发生最多的是手足综合症，发生率为：29．4％。结论 本组病例说明希罗达2000mg／d，分二次口服，连用14d，休息7d为一周期，在晚期肝癌中的临床应用是可行、安全而有效的。主要不良反应表现为手足综合症，可以对晚期肝癌进一步推广应用。     

Capecitabine and oral cyclophosphamide: A novel oral treatment combination for advanced cancer

Background: This dose escalation study assessed feasibility of a totally oral chemotherapy regimen using cyclophosphamide and capecitabine. The rationale for this combination was based on the observation that preclinical models of cyclophosphamide up‐regulated tumor thymidine phosphorylase and increased the activation of capecitabine. Methods: Eligible patients with advanced cancer were treated with oral cyclophosphamide and capecitabine on a 28‐day cycle. If no dose limiting toxicities (DLT) were encountered during the first two treatment cycles, the next patient group was assigned to the next highest dose level until the maximum tolerable dose (MTD) was determined. Results: Twenty‐seven patients entered treatment. The majority of non‐DLT were grades 1 and 2. DLT experienced in the first 8‐week observation period were grade 3 diarrhea (one patient, level III) and grade 3 emesis (two patients, level V). MTD was observed at level 5, 1331 mg/m²/day capecitabine days 1–28 with 125 mg/m²/day cyclophosphamide days 1–14 of the 28‐day cycle. The recommended phase II dose is therefore 1331 mg/m²/day capecitabine with 100 mg/m²/day cyclophosphamide. The best response evaluation showed four partial responses (breast, colon, ovary and pancreas). Conclusion: Cyclophosphamide and capecitabine can be combined at their full oral single agent dose with promising tolerability and activity.     

Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study.

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (GEM) combined with capecitabine (CAP) in untreated patients with inoperable or metastatic pancreatic cancer. PATIENTS AND METHODS: Fifty-three patients with pancreatic cancer (85% stage IV) were enrolled. Patients were treated with GEM 1000 mg/m2 on days 1 and 8 and CAP 1300 mg/m2 per day PO (per os), divided into two equal doses on days 1-14, in 21-day cycles. RESULTS: In an-intention-to-treat analysis, 10 (18.9%) objective partial responses were achieved (95% confidence interval 8.33% to 29.4%). Twenty-two (42%) patients had stable disease and 15 (28%) had progressive disease. The median response time was 3 months (range 1.5-7.0) and the median time to tumor progression was 6.5 months (range 3.5-15.5). Median overall survival time was 8 months (range 1.0-15.5) and 1-year survival was 34.8%. Pain improvement during treatment was observed in 23 of 43 (53%) patients, and eight of 18 (44%) patients who had been receiving opioids discontinued their use. Weight gain was observed in 12 of 33 (36%) patients. Grade 3 anemia occurred in five (9%) patients and grade 3-4 thrombocytopenia occurred in three (6%). Grade 3-4 neutropenia occurred in 13 (25%) and five (9%) patients, respectively, and two (4%) developed febrile neutropenia. Non-hematological toxicity was mild. CONCLUSION: In patients with pancreatic cancer, the combination of GEM with CAP is an active and well tolerated regimen that merits further evaluation in prospective randomized studies.     

卡培他滨单药治疗老年晚期胃癌临床分析

目的：观察卡培他滨单药治疗老年晚期胃癌的疗效和不良反应。方法：经病理确诊局部晚期或远处转移的老年晚期胃癌患者23例,应用卡培他滨单药化疗,剂量为1000mg／m^2,2次／日,连用14天,每3周为1个周期。结果：共完成治疗87个周期,最短1周期,最长9个周期。16例可评价疗效,部分缓解（PR）3例,稳定（SD）9例,进展（PD）4例,有效率18．8％,疾病控制率75％。中位疾病进展时间（TTP）5个月,中位总生存（OS）8个月,1年生存率22．7％。不良反应主要为胃肠道反应和手足综合征,大部分为I－Ⅱ度,耐受良好。结论：卡培他滨单药治疗老年晚期胃癌近期疗效确切,依从性好,不良反应可耐受。     

Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence‐free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non‐)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non‐academic hospitals were included. RFS and OS were analyzed with Kaplan‐Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five‐year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p = 0.91), adjusted HR = 0.99 (95%CI 0.68‐1.44); OS: 66% vs. 66% (p = 0.76), adjusted HR = 0.93 (95%CI 0.64–1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three‐year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR = 1.42 (95%CI 0.85–2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI 0.70–1.97)). Three‐year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11–3.84); OS: 65% vs. 80% (p = 0.01), adjusted HR = 2.00 (95%CI 1.12–3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.