含卡培他滨联合方案一线化疗后卡培他滨维持治疗转移性乳腺癌临床观察

目的:探讨转移性乳腺癌含卡培他滨联合方案一线化疗后继续卡培他滨维持化疗的疗效和毒副反应。方法:入组20例转移性乳腺癌患者,一线采用多西他赛/吉西他滨/长春瑞滨联合卡培他滨化疗6个周期,疗效评价无进展的患者采用卡培他滨维持化疗持续到疾病进展或出现不能耐受毒副反应为止。结果:一线治疗CR 1例,PR 7例,SD 12例,卡培他滨平均维持化疗周期为10个周期。中位PFS为12.2个月,中位TTP为7.7个月,中位OS为20.2个月。主要毒副反应为手足综合征、骨髓抑制、腹泻等,均可控制。结论:卡培他滨可作为转移性乳腺癌的维持治疗,可改善患者生存,毒副反应轻。     

Capecitabine maintenance therapy for XT chemotherapy-sensitive patients with metastatic triple-negative breast cancer

Objective： To investigate the efficacy and safety of capecitabine maintenance therapy（MT） after initial capecitabine plus docetaxel（XT） chemotherapy in patients with metastatic triple-negative breast cancer（m TNBC）.
Methods： Fifty-five m TNBC patients treated with XT chemotherapy between May 2007 and June 2013 were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, capecitabine was continued for 32 patients（MT）, while 23 patients remained without any treatment（nonMT）. We compared progression-free survival（PFS） and safety of both groups.
Results： The median PFS of 55 patients was 8.1 months, overall median PFS time of 32 patients in the capecitabine MT group and 23 in the non-MT group was 10.1 vs. 6.7 months（P=0.032）, respectively. When compared PFS time of maintenance treatment, single-agent capecitabine prolonged PFS by 7.1 months, for non-MT patients, the PFS without any treatment was 3.1 months, and this between-group difference was statistically significant（P=0.003）. Adverse events, including of hematologic toxicity, gastrointestinal toxicities, hand-foot syndrome and abnormal liver function were not significantly different between two groups.
Conclusions： After initial disease control was achieved with the XT combination chemotherapy, capecitabine MT can significantly prolong PFS time with a favorable safety profile in m TNBC patients.     

卡培他滨维持治疗转移性乳腺癌的疗效观察

目的:观察卡培他滨维持治疗转移性乳腺癌的疗效和毒副反应。方法:2009年10月-2013年7月,31例转移性乳腺癌一线或二线含卡培他滨联合化疗4-6个周期后,疾病达缓解或稳定的患者,接受卡培他滨维持治疗,卡培他滨1000mg/m2,d1-14,休息7天,21天为1个周期,维持化疗进展或不能耐受毒副反应者化疗停止,每个患者接受至少2个周期维持治疗。结果:卡培他滨维持治疗转移性乳腺癌有效率（RR）为6.5%,临床获益率（CBR）（＞6个月）为35.5%,疾病控制率（DCR）为74.2%,中位无进展生存期（PFS）为5.8个月。主要的毒副反应为手足综合征（HFS）,发生率为67.7%,多为Ⅰ-Ⅱ度,1例Ⅲ度患者应用大剂量维生素B6且卡培他滨减量后好转。Ⅲ-Ⅳ度白细胞、中性粒细胞下降分别为9.7%和12.9%,明显低于卡培他滨联合化疗时Ⅲ-Ⅳ度白细胞、中性粒细胞下降发生率的35.5%和38.7%（P＜0.05）。结论:卡培他滨是维持治疗转移性乳腺癌的有效药物,患者耐受性好,毒副反应较轻。     

口服小剂量环磷酰胺联合卡培他滨维持治疗晚期三阴性乳腺癌的疗效

目的:观察小剂量环磷酰胺（CTX）联合卡培他滨（CAP）维持治疗晚期三阴性乳腺癌的疗效及安全性。方法:回顾性分析我院收治的经含卡培他滨方案两药联合化疗后达临床稳定的晚期三阴性乳腺癌患者68例,实验组34例给予口服环磷酰胺 50 mg/d,d8~21,每3周重复,联合卡培他滨1 000 mg/m2,bid,d1~14,休息7天。对照组34例患者仅给予口服卡培他滨单药维持治疗。观察2组患者的ORR、DCR、TTP、安全性及对生活质量的影响。结果:经维持治疗后实验组ORR 为29.4%,DCR为85.3%;对照组ORR 为14.7%,DCR为64.7%。实验组中位TTP为12个月,明显高于对照组中位TTP 6.9个月(P＜0.05)。两组的主要不良反应为手足综合征,实验组的胃肠道反应及血液学毒性稍高于对照组,均为Ⅰ-Ⅱ度。两组患者的生活质量评分均较治疗前明显提高,治疗后组间差异无统计学意义(P＞0.05)。结论:口服小剂量环磷酰胺联合卡培他滨维持治疗晚期三阴性乳腺癌有较好的疗效,不良反应可以耐受,可作为复发转移较快的晚期三阴性乳腺癌患者维持治疗的一种选择,具有一定的临床推广应用价值。     

Hormonal therapy might be a better choice asmaintenance treatment thancapecitabine afterresponse toifrst-line capecitabine-based combination chemotherapy forpatients withhormone receptor-positive andHER2-negative,metastatic breast cancer

Background:Both hormonal therapy (HT) and maintenance capecitabine monotherapy (MCT) have been shown to extend time to progression (TTP) in patients with metastatic breast cancer (MBC) after failure of taxanes and anthracycline?containing regimens. However, no clinical trials have directly compared the effcacy of MCT and HT after response to ifrst?line capecitabine?based combination chemotherapy (FCCT) in patients with hormone receptor (HR)?positive and human epidermal growth factor receptor 2 (HER2)?negative breast cancer. Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, in Beijing, China. The median number of ifrst?line chemotherapy cycles was 6 (range, 4–8); combined agents included taxanes, vinorelbine, or gemcitabine. Of these 138 patients, 79 received MCT, and 59 received HT. Single?agent capecitabine was administered at a dose of 1250mg/m2 twice daily for 14days, followed by a 7?day rest period, repeated every 3weeks. Of the 59 patients who received HT, 37 received aromatase inhibitors (AIs), 8 received selective estrogen receptor modulators (SERMs), and 14 received goserelin plus either AIs or SERMs. We then compared the MCT group and HT group in terms of treatment effcacy. Results:With a median follow?up of 43months, patients in the HT group had a much longer TTP than patients in the MCT group (13 vs. 8months,P=0.011). When TTP was adjusted for age, menopausal status, Karnofsky performance status score, disease?free survival, site of metastasis, number of metastatic sites, and response status after FCCT, extended TTP was still observed for patients in the HT group (hazard ratio: 0.63; 95% conifdence interval: 0.44–0.93;P=0.020). We also observed a trend of overall survival advantage for patients in the HT group vs. patients in the MCT group, but the difference was not signiifcant (43 vs. 37months,P=0.400). In addition, patients in the HT group gen?erally tolerated the treatment well, whereas patients in the MCT group experienced grades 3–4 adverse events, the most frequent of which were hand?foot syndrome (15.8%) and hematologic abnormalities (7.6%). Conclusion: For HR?positive and HER2?negative MBC patients, HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.     

吉西他滨联合卡培他滨治疗耐药转移性乳腺癌56例临床分析

为了评估吉西他滨(GEM)和卡培他滨(CAP)3周联合化疗方案在蒽环类和(或)紫杉类耐药的转移性乳腺癌(MBC)患者中的有效性和毒性,对56例既往用过蒽环类和紫杉类的MBC患者给予GEM1000mg/m2,静脉滴入30min,d1、d8;CAP2000mg/m2,分2次口服,d1～d14,每3周为1个周期。所有患者均评估毒性,至少用过2个周期的患者评估疗效。结果:56例患者共完成196个周期化疗,中位化疗周期数为3.5个周期。完全缓解4例,部分缓解22例,稳定18例,进展12例,有效率为46.4%(26/56)。最常见的毒副反应为骨髓抑制和手足综合征。初步研究结果提示,GEM和CAP联合化疗方案在既往接受过蒽环类和紫杉类药物的MBC患者中是安全有效的,血液学和非血液学毒性都可耐受。     

曲妥珠单抗联合吉西他滨治疗ＨＥＲ２阳性的转移性乳腺癌

目的：探讨曲妥珠单抗（赫赛汀）联合吉西他滨（ＧＥＭ）治疗表皮生长因子受体２（ＨＥＲ２）阳性的转移性乳腺癌（ＭＢＣ）的疗效和不良反应。方法：ＨＥＲ２阳性的ＭＢＣ女性患者９例,给予ＧＥＭ１０００ｍｇ／ｍ^２,静脉滴注,ｄ１、ｄ８、ｄ１５,４周重复;赫赛汀静脉滴注,首次４ｍｇ／ｋｇ,其后每周１次,２ｍｇ／ｋｇ,连续使用。结果：９例患者中,ＣＲ１例（１１.１％）,ＰＲ６例（６６.７％）,ＳＤ和ＰＤ各１例（１１.１％）,有效率（ＲＲ）为７７.８％,疾病控制率（ＤＣＲ）为８８.９％;中位肿瘤进展时间（ＴＴＰ）为１８个月,中位总生存时间（ＯＳ）为２３个月。主要毒性反应是骨髓抑制和消化道反应,且均为Ⅰ ～Ⅱ度。结论：赫赛汀联合吉西他滨对于难治性转移性乳腺癌是有效且安全的治疗方案。     

Phase 2 trial of a novel capecitabine dosing schedule in combination with bevacizumab for patients with metastatic breast cancer

BACKGROUND:

Capecitabine has antitumor activity in metastatic breast cancer (MBC); however, its optimal dose and schedule remain unclear. Mathematical modeling predicts that a capecitabine schedule 7 days of treatment followed by 7 days of rest (7—7) will improve efficacy and minimize toxicity. Bevacizumab has demonstrated the ability to improve outcomes when it is added to chemotherapy, including capecitabine, in the first‐line and second‐line settings.

METHODS:

Patients with measurable MBC received oral capecitabine (2000 mg twice daily; 7—7), and intravenous bevacizumab (10 mg/kg every 2 weeks). The primary endpoint was the response rate. Secondary endpoints included toxicity, the clinical benefit rate, and progression‐free survival (PFS).

RESULTS:

Forty‐one patients were treated. After a median of 7 cycles (range, 1‐32 cycles), partial responses were observed in 20% of patients, and stable disease for ≥6 months was noted in 35% patients. The median PFS was 8 months. The most common treatment‐related toxicities were hand‐foot syndrome (49% grade 2, 20% grade 3/4) hypertension (12% grade 2, 10% grade 3/4), and fatigue (12% grade 2, 2% grade 3/4). Diarrhea (5% grade 2, 0% grade 3/4), nausea (0% grade 2‐4), and vomiting (0% grade 2‐4) were rare.

CONCLUSIONS:

Capecitabine administered for 7 days followed by a 7‐day rest in combination with bevacizumab had modest efficacy and an acceptable toxicity profile in patients with MBC. Gastrointestinal toxicity with this schedule was minimal. Cancer 2011;. © 2011 American Cancer Society.     

Multicenter phase II study of combination chemotherapy with capecitabine and intravenous vinorelbine in patients with pretreated metastatic breast cancer

Background: Capecitabine and i.v. vinorelbine are both active in metastatic breast cancer with non‐overlapping toxicities. This study examined the efficacy and safety of the combination of these agents in patients with pretreated metastatic breast cancer. Methods: Patients previously treated for breast cancer, maximum of one prior metastatic regimen, received capecitabine 1000 mg/m² b.d. for days 1–14 and vinorelbine 25 mg/m² i.v. days 1 and 8 every 21 days. All patients had measurable disease and adequate baseline organ function. The primary endpoint was response and secondary endpoints time to progression, duration of response, survival and safety. Results: Twenty‐two patients (median age 56 years) received a median of six cycles. All patients had received anthracyclines and 64% taxanes. Objective responses were seen in 7/21 (33%, 95% confidence interval [CI] 18–57%), with two complete responses; stable disease was seen in 5/21 (24%, 95% CI 8–42%). Median duration of response was 6.9 months (95% CI 4.7–13.1), time to progression was 5.8 months (95% CI 2.8–6.8) and survival was 13.5 months (95% CI 6.9–19.9). The median dose intensity of vinorelbine was 75% of the intended dose and of capecitabine 85% of intended dose. The main toxicity was myelosuppression including 16 episodes of G3–4 neutropenia in 11 patients (50%). Other toxicities were generally mild to moderate. Conclusion: The combination of capecitabine and i.v. vinorelbine is active and well tolerated in patients with pretreated metastatic breast cancer. The recent availability of oral vinorelbine provides an opportunity to explore a fully oral combination.     

Phase ii trial of a metronomic schedule of docetaxel and capecitabine with concurrent celecoxib in patients with prior anthracycline exposure for metastatic breast cancer

Background

This phase ii clinical trial examined the activity of a metronomic dosing schedule of docetaxel and capecitabine chemotherapy in patients with advanced breast cancer. Patients also received daily oral celecoxib in an effort to improve outcome measures and to ameliorate some of the common side effects of chemotherapy.

Methods

Patients received docetaxel at a starting dose of 15 mg/m² weekly, oral capecitabine 1250 mg/m² once daily, and oral celecoxib 200 mg twice daily. The primary endpoint was clinical benefit: percentage of patients experiencing either an objective response or stable disease (sd) for more than 6 months. In the absence of significant neutropenia, the dose of docetaxel was escalated after 4 and 8 weeks of treatment. Therapy was given until disease progression or development of unacceptable toxicity. The level of thymidine phosphorylase expression in peripheral white blood cells of patients was measured before and during treatment to determine the effect on this capecitabine-activating enzyme.

Results

Of 47 patients enrolled, 38 (81%) completed treatment to a disease endpoint. No complete responses were achieved, but 13 of the 38 patients (34%) experienced a partial response, and another 3 patients (8%) experienced sd for more than 6 months. The clinical benefit rate was therefore 42% (95% confidence interval: 27% to 57%). The median time to disease progression for all evaluable patients was 3.6 months (range: 0.9–21.7 months). The most common nonhematologic toxicities were diarrhea, plantar– palmar erythrodysesthesia, fatigue, mucositis, and vomiting. Most patients (89%) received combination chemotherapy until disease progression.

Conclusions

The present study demonstrates that metronomic docetaxel–capecitabine chemotherapy with daily celecoxib can produce significant anticancer activity, with predictable toxicity. Efficacy fell short of expectations, with outcome measures being similar to those obtained when the study agents are given in conventional dosing. Furthermore, there is mounting evidence to indicate that a low dose of taxanes fails to induce thymidine phosphorylase expression, an effect believed to be important in achieving therapeutic synergism when taxanes are given concurrently with capecitabine.     

Phase II trial of simple oral therapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: SWOG S0430

Background.

Interest in oral agents for the treatment of metastatic breast cancer (MBC) has increased because many patients prefer oral to i.v. regimens. We evaluated a simple oral combination of capecitabine with cyclophosphamide (CPA) for MBC.

Methods.

The trial was designed to determine whether or not combination therapy would achieve a 42% response rate (RR) using the Response Evaluation Criteria in Solid Tumors (RECIST) in MBC. Patients with two or fewer prior chemotherapy regimens for MBC were eligible. Those with estrogen receptor–positive MBC had to have progressed on endocrine therapy. Patients had measurable disease or elevated mucin (MUC)-1 antigen and received CPA, 100 mg daily on days 1–14, and capecitabine, 1,500 mg twice daily on days 8–21, in 21-day cycles.

Results.

In 96 eligible patients, the median progression-free survival (PFS) interval was 5.9 months (95% confidence interval [CI], 3.7–8.0 months) and median overall survival (OS) time was 18.8 months (95% CI, 13.1–22.0 months). The RR was 36% (95% CI, 26%–48%) in 80 patients with measurable disease. The MUC-1 antigen RR was 33% (95% CI, 20%–48%), occurring in 15 of 46 patients with elevated MUC-1 antigen. Toxicity was mild, with no treatment-related deaths.

Conclusions.

PFS, OS, and RR outcomes with capecitabine plus CPA compare favorably with those of capecitabine monotherapy and combination therapy with bevacizumab, sorafenib, or ixabepilone. The addition of these other agents to capecitabine does not improve OS time in MBC patients, and this single-arm study does not suggest that the addition of CPA to capecitabine has this potential in an unselected MBC population. When OS prolongation is the goal, clinicians should choose single-agent capecitabine.     

相同剂量长春瑞滨序贯或联合卡培他滨一线治疗转移性乳腺癌的Ⅱ期随机对照临床试验

Objective  

It remains unclear whether simultaneous use of two chemotherapeutic drugs is better than sequential use. This trial was designed to explore efficacy and safety of sequential vs simultaneous use of vinorelbine and capecitabine at the same dosage as first-line therapy in metastatic breast cancer (MBC).     

多西紫杉醇联合卡培他滨治疗蒽环类药物耐药性晚期乳腺癌的初步临床结果

目的观察多西紫杉醇(docetaxel)联合卡培他滨(capecitabine)治疗蒽环类耐药性晚期乳腺癌的疗效.方法2002年6月～2003年10月,以此方案治疗蒽环类药物耐药的晚期乳腺癌16例.全组化疗共52周期,中位周期数3周期(2～6周期).结果CR 2例,PR 7例,SD 4例,PD 3例,总有效率(CR PR)56.2%.全组中位缓解期5个月(2～14个月).主要剂量毒性为骨髓抑制、胃肠道反应和手足综合征,骨髓抑制以白细胞减少为主,Ⅲ～Ⅳ度白细胞减少发生率为18.7%.结论多西紫杉醇联合卡培他滨对蒽环类药物耐药的转移性乳腺癌有较好的疗效,且毒性可以耐受,可以考虑作为解救化疗方案.     

Phase II study of an all-oral combination of vinorelbine with capecitabine in patients with metastatic breast cancer

Purpose  Combination of intravenous (i.v.) vinorelbine and capecitabine was shown to be feasible and effective in metastatic breast cancer (MBC). In an effort to improve patient convenience and to prolong infusion-free survival, we investigated in first-line treatment a regimen combining oral vinorelbine and capecitabine in a phase II study. Patients and methods  Fifty-two patients (median age, 60 years) with MBC received the combination consisting of oral vinorelbine 60 mg/m² on days 1, 8 and 15 plus capecitabine 1,000 mg/m² bid given from day 1 to day 14 in an open-label, multicentre phase II study [the recommended doses were established in a phase I study (Nolé et al. in Ann Oncol 17:332–339, 2006)]. Cycles were repeated every 3 weeks. Results  Seventy-nine percent of the patients had received prior adjuvant chemotherapy and 81% presented with visceral involvement. The median number of administered cycles per patient was 7 (range 1–18). Twenty-three responses were documented and validated by an independent panel review, yielding response rates of 44.2% (95% CI, 30.5–58.7) in the 52 enrolled patients and 54.8% (95% CI, 38.7–70.2) in the 42 evaluable patients. Median progression-free survival and median overall survival were 8.4 and 25.8 months, respectively. Neutropenia was the main dose-limiting toxicity but complications were uncommon, only one patient having experienced febrile neutropenia. Other frequently reported adverse events included, fatigue, nausea, vomiting, diarrhoea and constipation, stomatitis and hand-foot syndrome, which were rarely severe. Conclusions  This regimen combining oral vinorelbine with capecitabine is effective and manageable in the first-line treatment of MBC. Oral vinorelbine on days 1, 8 and 15 with capecitabine from days 1 to 14 every 3 weeks represents a convenient option which offers an all-oral treatment to the patients and prolongs their infusion-free survival.     

卡培他滨治疗蒽环类及紫杉类耐药的复发转移性乳腺癌的临床观察

目的:观察卡培他滨对蒽环类、紫杉类耐药的复发转移性乳腺癌的作用。方法:40例复发转移性乳腺癌患者,均经过蒽环类及紫杉类治疗后出现疾病进展。给予卡培他滨2510mg/(m2·d),分2次口服,连服2周,3周为1个周期。至少2个周期后评价疗效。结果:本组化疗均数为4个周期。CR1例,PR8例,SD23例,PD7例,有效率23.1%,疾病控制率(CR PR SD)为82.0%(32/39);TTP3.4个月;中位生存时间11.2个月。常见不良反应为手足综合征(70.0%)、皮肤色素沉着(60.0%)、恶心呕吐(52.5%)、腹泻(42.5%),2例出现3～4级严重腹泻而住院治疗。结论:卡培他滨对蒽环类、紫杉类耐药的复发转移性乳腺癌仍有一定的疗效,耐受性较好。     

Phase II study of capecitabine in combination with paclitaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer

The addition of oral capecitabine to docetaxel improves response rate, time to progression (TTP) and overall survival in anthracycline-pretreated metastatic breast cancer (MBC). This phase II study evaluates the efficacy and safety of a 21-day cycle of oral capecitabine (1000 mg m(-2) twice daily, days 1-14) plus i.v. paclitaxel (175 mg m(-2), day 1) in anthracycline-pretreated advanced/MBC. In all, 73 patients were enrolled at 13 Swedish and Spanish centres. The objective response rate was 52% (95% confidence interval (CI): 40-63%) in the intent-to-treat population, including complete responses in 11%. Disease was stabilised in a further 29%. The median time to disease progression (TTP) was 8.1 months and the median overall survival was 16.5 months. The combination was generally well tolerated with a predictable safety profile. The most common treatment-related nonhaematological adverse events were hand-foot syndrome (42%), alopecia (30%) and diarrhoea (26%). The only treatment-related Grade 3/4 adverse events occurring in >5% of patients were alopecia (22%) and hand-foot syndrome (11%). Grade 3/4 neutropenia and lymphocytopenia were reported in 12 and 14% of patients, respectively. Capecitabine plus paclitaxel is highly active with a favourable safety profile in anthracycline-pretreated MBC.     

Efficacy and safety of single agent capecitabine in pretreated metastatic breast cancer patients from the French compassionate use program

Background. A retrospective source review identifying predictive factors and assessing safety and efficacy in pretreated metastatic breast cancer (MBC) patients treated with capecitabine in a French compassionate-use program. Patients and methods. 197 patients received capecitabine at an initial total dose 0.25–3.0g/m²/day, twice daily for 14 consecutive days, every 3weeks. Results. Median patient age was 56years (range, 31–88), 19% had performance status (PS) 3–4. Prior palliative and adjuvant treatment was reported in 96 and 61% of patients respectively. Best overall response rate (ORR) was 15% (95% confidence interval [CI], 11–21%) and 49% had benefit (CR, PR or SD). Median time to progression (TTP) and overall survival were 4.8 and 14.7 months, respectively. Median TTP in responders was 8.9months (95%CI 6.1–11.7). Grade 3/4 neutropenia and grade 3 thrombocytopenia occurred in 8 and 3% of patients respectively. Hand-foot syndrome (grade 3/4 in 16% of patients), diarrhea, stomatitis and asthenia were prevalent. Multivariate analysis showed ORR was significantly influenced by PS2 (p=0.004), time from metastases diagnosis to capecitabine treatment (p=0.015) and presence of liver metastases at inclusion (p=0.047). Abnormal liver function tests at baseline were associated with severe thrombocytopenia and anemia. Four treatment-related deaths occurred. Conclusion. Capecitabine is active in heavily pretreated MBC patients and has a favorable toxicity profile with the added advantage of being an oral drug administered in an outpatient setting.     

Efficacy of S-1 in heavily pretreated patients with metastatic breast cancer: cross-resistance to capecitabine

Background  It is not clear what the optimal treatment of chemotherapy is for patients with heavily treated metastatic breast cancer (MBC). We have retrospectively examined the efficacy and safety of S-1 in patients with MBC who had been previously treated with anthracycline, taxane, and capecitabine. Methods  Patients with MBC who had been administered S-1, an oral modulated compound containing a fluoropyrimidine derivative, between November 2001 and June 2003 at the Cancer Institute Hospital were retrospectively reviewed. S-1 at a standard dose of 50 mg/body was administered twice daily for four weeks, followed by a two-week rest period. This was repeated every six weeks until disease progression or unacceptable toxicity. Results  Thirty-five patients were assessed. The patients were heavily pretreated with anthracycline (100%), taxane (paclitaxel or docetaxel) (100%), capecitabine (100%), vinorelbine (71%), and mitomycin (69%). Median follow-up time of patients was 9.6 months (range, 1.2–26.6). ORR was 3% (95% confidence interval: 0–9%), and CBR was 20% (95% confidence interval: 6–33%). Time to treatment failure was 2.8 months. Overall survival was 21.4 months. Grade 1 or 2 adverse events were observed in 17% and 13%, respectively. Grade 3 events occurred as anorexia (9%), nausea (9%), vomiting (9%), diarrhea (14%), fatigue (3%), and elevation of AST/ALT (3%). No grade 3 was seen as hand-foot syndrome. Neither grade 3 nor 4 was observed in bone marrow suppression. Conclusions  S-1 was fairly well tolerated, but demonstrated very limited activity in capecitabine-pretreated patients who had already been exposed to anthracycline and taxane. It was suggested that S-1 clinically exhibited cross-resistance to capecitabine.     

Efficacy and safety of capecitabine-based first-line chemotherapy in advanced or metastatic breast cancer: a meta-analysis of randomised controlled trials

We sought to evaluate the efficacy and safety of capecitabine-based therapy as first-line chemotherapy in advanced breast cancer. Randomised controlled trials of capecitabine monotherapy or combined treatment were included in the meta-analysis. PubMed, EMBASE, the Cochrane Library database and important meeting summaries were searched systematically. Outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and grades 3–4 drug-related adverse events.Nine trials with 1798 patients were included. The results indicated a significant improvement with capecitabine-based chemotherapy compared with capecitabine-free chemotherapy in ORR (relative risk [RR] 1.14, 95% confidence interval [CI] 1.03 to 1.26, P = 0.013) and PFS (hazard ratio [HR] 0.77, 95% CI 0.69 to 0.87, P < 0.0001). Overall survival favoured capecitabine-based chemotherapy, but this was not significant. There were more incidences of neutropenia and neutropenic fever in the capecitabine-free chemotherapy group and more vomiting, diarrhoea and hand–foot syndrome in the capecitabine-based chemotherapy group. There were no significant differences in nausea, fatigue, cardiotoxicity or mucositis/stomatitis between the two treatment regimens.Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS. Capecitabine-based regimens are suitable as first-line treatment for patients with advanced breast cancer.     

Clinical observation of capecitabine monotherapy in elderly patients with advanced breast cancer

Objective The aim of the study was to evaluate the safety and efficacy of capecitabine mono-chemotherapy in elderly patients with advanced breast cancer. Methods The data from 36 cases of capecitabine monotherapy in elderly patients with advanced breast cancer were retrospectively analyzed. Oral administration of capecitabine 2000 mg/m2 twice daily(D1–14) for 21 days constituted a cycle. The effect of the disease and main adverse reactions were evaluated every 2 cycles. Results The data from 36 elderly patients were studied. The median number of chemotherapy cycles was 4. The total effective rate was 30.6%(11/36) and the disease control rate was 72.2%(26/36). The number of patients with clinical complete remission was 2, clinical partial response was 9, stable disease was 15, and progressive disease was 10. Where treatment was effective, the median time to progression was 6 months and the median overall survival was 9.5 months. The main adverse events were gastrointestinal reactions, bone marrow suppression, and oral mucositis; most of the reactions were grade 1 to 2. Grade 3 to 4 adverse reactions included granulocytopenia in 2 patients(12.5%) and hand-foot syndrome in 1 patient(6.7%).Conclusion Capecitabine monotherapy was effective in controlling disease progression, and adverse reactions were tolerated by elderly patients with advanced breast cancer.