Correlations of survival with progression-free survival,response rate,and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

Background:

The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS).

Methods:

We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated.

Results:

Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r²=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r²-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents.

Conclusions:

The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development.     

Efficacy of capecitabine-based combination therapy and single-agent capecitabine maintenance therapy in patients with metastatic breast cancer

Objective

The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer (MBC).

Patients and methods

A total of 98 MBC patients were treated with capecitabine combined with vinorelbine (NX).

Results

The median number of treatment was 6 cycles (1-7 cycles). There were two cases of complete remission (CR), 58 partial remission, 27 stable disease (SD), 11 progression disease. The overall response rate (ORR) (CR + PR) was 61.2%. The clinical benefit rate (CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR (CR + PR) was 4%. The CBR was 48%. The median progression-free survival (PFS) was 12 months. In maintenance therapy or not, the median post metastasis survival rate (MSR) was 63 and 28 months, respectively. In the combination therapy group, the major grade 3/4 toxicities included hand-foot syndrome (3.1%), skin pigmentation (2.0%), diarrhoea and abdominal distension (5.1%), stomatitis (1.0%), and leukopenia (20.4%).

Conclusions

Capecitabine-based combination therapy and single-agent capecitabine maintenance therapy were well tolerated and effective to MBC.     

Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials

The purpose of this study was to estimate in all randomised trials the relative risk of overall response rate (ORR), clinical benefit (CB), time to progression (TTP), overall survival (OS), and toxicity of aromatase inhibitors (AI), compared with tamoxifen (Tam) as first-line endocrine therapy in postmenopausal metastatic breast cancer (PMBC) women. Prospective randomised studies were searched through computerised queries of MEDLINE, EMBASE, and the American Society of Clinical Oncology (ASCO) abstract database. Relative risk, 95% confidence interval, and heterogeneity were derived according to the inverse variance and Mantel-Haenszel method and Q statistics. Six phase III prospective randomised trials including 2787 women were gathered. A significant advantage in ORR (P = 0.042), TTP (P = 0.007), and CB (P = 0.001) in favour of AI over Tam was detected at the fixed effects model. These results were not significant at the random effects model, owing to the significant heterogeneity. On the contrary, no difference was registered for OS (P = 0.743) with no significant heterogeneity. Regarding toxicity, Tam caused more frequently thromboembolic events (P = 0.005) and vaginal bleeding (P = 0.001) compared with AI. Aromatase inhibitors appear to be superior to Tam as first-line endocrine option in PMBC women. Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones. Investigators should assess heterogeneity of trial results before deriving summary estimates of treatment effect.     

Efficiency and safety of trastuzumab plus chemotherapy in Her-2 overexpressing metastatic breast cancer patients

Objective： The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer （MBC） patients. The primary endpoint was overall response rate （ORR） and the second endpoint was clinical benefit rate （CBR） and toxcities. Methods： Estrogen recep- tor （ER） （-）, progesterone receptor （PR） （-）, Her-2 （＋＋＋） patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group （H group） and 75 of them were assigned to the Control group （C group）. They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results： Response rate （RR） of the H group and the C group were 51.0% and 24.0% separately, and the difference were statistically significant （P 〈 0.05）. CBR of the two groups were 76.4% （H group） and 64.0% （C group）, had significant difference （P 〈 0.05）. Complete response rate （CRR） of the two groups were 21.5% and 6.6%, there were no significant difference between the two groups （P = 0.055）. Grade 3-4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy （17.6%） and 4 patients with chemotherapy （5.4%）, with no statistical significance （P = 0.054）. In the subgroup of antharcycline-containing regimens, Grade 1-4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracyciine contained chemotherapy （H ＋ ACCT arm; 40.9%, g/22）], and 4 patients in the antharcycline- containing chemotherapy arm （ACCT arm; 12.5%, 4/32）. There was statistical significant difference between the two arms （P 〈 0.05）. Grade 3--4 cardiac toxicity, the occurance rates were 18.1% （4/22） in H ＋ ACCT arm and 6.3% （2/32） in ACCT arm, and there was no significant statistical difference （P = 0.352）. Grade 3-4 granulocytopenia     

Sequential doxorubicin and docetaxel as first-line treatment in metastatic breast cancer: a GEICAM-9801 phase II study

Purpose. To evaluate the efficacy and the toxicity profile of the sequential administration of doxorubicin and docetaxel as first-line chemotherapy in metastatic breast cancer (MBC). Patients and methods. Eighty-one patients received a total of 436 cycles of chemotherapy: 236 of doxorubicin (75 mg/m²) and 200 of docetaxel (100 mg/m² every 21 days). The first 35 patients received doxorubicin every 14 days with G-CSF support, and in the other 46 cases doxorubicin was administered every 21 days without G-CSF. Results. After entire treatment the overall response rate was 65% (18 complete responses). With a median follow-up of 19 months (range, 1–48 months), the median time to progression was 11.3 months and the median survival time was 31 months. As expected, febrile neutropenia was the most important toxicity and it appeared in 26 cycles (6%) and 19 patients (23%). In the patients that received doxorubicin every 14 days, the febrile neutropenia incidence was higher during docetaxel treatment, especially after its first administration. Conclusions. The dose and schedule of doxorubicin and docetaxel used in this trial seems to be active in first-line treatment of patients with MBC. The toxicity profile appears to be better than observed with concomitant schedules.     

Survival benefit of chemotherapy in metastatic colorectal cancer: a meta-analysis of randomized controlled trials

To estimate the magnitude of benefit of chemotherapy in prolonging survival for patients with metastatic colorectal cancer, a meta-analysis of randomized controlled trial was performed. A systematic search was performed to identify randomized trials comparing chemotherapy with observation or supportive care alone. Trials were assessed for quality of reporting, publication bias and heterogeneity. Relative risks for outcomes from published data were pooled using a random-effects model. Seven trials with 614 patients were included. All trials used fluoropyrimidine-based chemotherapy, through a variety of routes and schedules, including intravenous, intra-portal and hepatic arterial infusion. Compared with the 'no-chemotherapy' arm, chemotherapy significantly reduced 1-year mortality (risk ratio 0.69; 95% confidence interval (CI) 0.60-0.81, P < 0.00001). The mortality at 2 years was not significantly different (risk ratio 0.93; 95% CI 0.87-1.00, P = 0.053). Between-trial comparisons demonstrated benefit with a variety of routes and schedules. Chemotherapy significantly prolongs 1-year survival for patients with metastatic colorectal cancer, and should be offered to those with good performance status.     

The role of biological therapy in metastatic colorectal cancer after first-line treatment: a meta-analysis of randomised trials

Purpose:

Biologic agents have achieved variable results in relapsed metastatic colorectal cancer (mCRC). Systematic meta-analysis was undertaken to determine the efficacy of biological therapy.

Methods:

Major databases were searched for randomised studies of mCRC after first-line treatment comparing (1) standard treatment plus biologic agent with standard treatment or (2) standard treatment with biologic agent with the same treatment with different biologic agent(s). Data were extracted on study design, participants, interventions and outcomes. Study quality was assessed using the MERGE criteria. Comparable data were pooled for meta-analysis.

Results:

Twenty eligible studies with 8225 patients were identified. The use of any biologic therapy improved overall survival with hazard ratio (HR) 0.87 (95% confidence interval (CI) 0.82–0.91, P<0.00001), progression-free survival (PFS) with HR 0.71 (95% CI 0.67–0.74, P<0.0001) and overall response rate (ORR) with odds ratio (OR) 2.38 (95% CI 2.03–2.78, P<0.00001). Grade 3/4 toxicity was increased with OR 2.34. Considering by subgroups, EGFR inhibitors (EGFR-I) in the second-line setting and anti-angiogenic therapies (both in second-line and third-line and beyond settings) all improved overall survival, PFS and ORR. EGFR-I in third-line settings improved PFS and ORR but not OS.

Conclusions:

The use of biologic agents in mCRC after first-line treatment is associated with improved outcomes but increased toxicity.     

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 and safety of anlotinib as a third-line treatment of advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

Anlotinib is a novel multitarget tyrosine kinase inhibitor, which has been indicated to inhibit both tumor angiogenesis and signal transduction pathways associated with proliferation. The main proposed mechanism of anlotinib inhibiting tumor angiogenesis is that anlotinib inhibits the activation of VEGFR2, PDGFRβ and FGFR1, and downstream ERK signal transduction. The aim of the present study was to systematically evaluate the efficacy and safety of third-line treatment with anlotinib for advanced non-small cell lung cancer (NSCLC). To meet this aim, studies published up to February 2022 were searched in PubMed, Web of Science, the Cochrane Library and several Chinese databases. Only randomized controlled trials (RCTs) were included and a metaanalysis was performed using RevMan 5.3 software. A total of 18 RCTs were identified and included in the present study, comprising 1,658 patients. The anlotinib treatment group was indicated to be better than the control group at prolonging progression-free survival [hazard ratio (HR), 0.33; 95% confidence interval (95% CI), 0.28-0.37] and overall survival (HR, 0.70; 95% CI, 0.60-0.81). Anlotinib also provided a significant improvement in the disease control rate [risk ratio (RR), 1.51; 95% CI, 1.27-1.79], objective response rate (1.75, 95% CI, 1.51-2.03) and Karnofsky performance status (mean difference, 9.85; 95% CI, 6.26-13.43). Compared with the control group, the incidence of adverse events (AEs), such as hypertension and hemoptysis, was increased by anlotinib. Through subgroup analysis, it was determined that, compared with the placebo, the incidence of AEs was increased by anlotinib, although compared with other therapeutic drugs, no significant differences were observed. In conclusion, the findings of the present study suggested that the thirdline treatment of advanced NSCLC with anlotinib is more effective compared with other control measures and that the AEs are also controllable. However, given the limitations of the quantity and the quality of the included studies, further studies are required to gain a more complete understanding of the effects of anlotinib.     

Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer

Purpose To evaluate the efficacy and safety of erlotinib in advanced breast cancer. Experimental design Multicenter, phase II study of erlotinib (150 mg orally daily). Cohort 1: progression after anthracyclines, taxanes, and capecitabine (n = 47). Cohort 2: progression after >1 chemotherapy for advanced-stage disease (n = 22). Primary endpoint was response rate (World Health Organization criteria). Secondary endpoints were safety, time to progression, and survival. Results One patient in each cohort (n = 2, 3.0%) had a partial response. Response duration was 17 weeks for the Cohort 1 patient and 32 weeks for the Cohort 2 patient. Median time to progression was 43 days for Cohort 1 (range 1–204) and 43 days for Cohort 2 (range 25–419). Common adverse events were diarrhea, rash, dry skin, asthenia, nausea, anorexia. Conclusion Erlotinib had minimal activity in unselected previously treated women with advanced breast cancer. Predictive factors are needed to identify breast cancer patients who may derive benefit from erlotinib treatment.     

All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial

Background:

This multicentre, international phase II trial evaluated the efficacy and safety profile of a first-line combination of oral vinorelbine plus capecitabine for women with metastatic breast cancer (MBC).

Methods:

Patients with measurable, HER2-negative disease received, as a first line in metastatic setting, 3-weekly cycles of oral vinorelbine 80 mg m⁻² (after a first cycle at 60) on day 1 and day 8, plus capecitabine 1000 mg m⁻² (750 if ⩾65 years of age) twice daily, on days 1–14. Treatment was continued until progression or unacceptable toxicity.

Results:

A total of 55 patients were enrolled and 54 were treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST) in 49 evaluable patients was 51% (95% confidence interval (CI), 36–66), including complete response in 4%. The clinical benefit rate (response or stable disease for ⩾6 months) was 63% (95% CI, 48–77). The median duration of response was 7.2 months (95% CI, 6.4–10.2). After a median follow-up of 41 months, median progression-free survival was 8.4 months (95% CI, 5.8–9.7) and median overall survival was 29.2 months (95% CI, 18.2–40.1). Treatment-related adverse events were manageable, the main grade 3–4 toxicity was neutropaenia (49%); two patients experienced febrile neutropaenia and three patients had a neutropaenic infection (including one septic death). A particularly low rate of alopaecia was observed.

Conclusion:

These results show that the all-oral combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for MBC.     

多西紫杉醇联合卡培他滨治疗蒽环类耐药的晚期乳腺癌

目的：观察多西紫杉醇联合卡培他滨方案治疗对蒽环类耐药的晚期乳腺癌的疗效及毒副反应。方法：24例患者给予多西紫杉醇75mg/m^2静滴d1,卡培他滨1650mg/m^2.d,口服,d1-d14。21天为1周期,至少用2个周期,中位化疗周期数3个（2-4周期）。结果：总有效率41.7%,疾病控制率为83.3%,中位生存期16.5个月,主要毒副作用为骨髓抑制和脱发。结论：多西紫杉醇联合卡培他滨治疗对蒽环类耐药的晚期乳腺癌疗效好,毒副作用轻,是治疗对蒽环类耐药晚期乳腺癌较好的方案。     

Phase II study of capecitabine and oxaliplatin as first-line treatment in advanced colorectal cancer.

BACKGROUND: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer. The aim of this phase II study is to determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced non-pretreated colorectal cancer. PATIENTS AND METHODS: Forty-three chemotherapy-na?ve patients were enrolled. Capecitabine 2500 mg/m(2)/day was administered orally twice a day continuously for 14 days and oxaliplatin 120 mg/m(2) was administered as a 2-h infusion on day 1, repeated every 3 weeks. RESULTS: Forty-three patients were assessable for toxicity and 39 for clinical activity: the main toxicity was grade 3 or 4 diarrhea, which occurred in 28% of the patients. The response rates were 44% [95% confidence interval (CI), 29.3% to 59.0%] and 48.7% (95% CI 33.0% to 64.4%) (intention-to-treat and per protocol analysis, respectively). The median overall survival was 20 months (95% CI 12-28). CONCLUSIONS: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer; therefore, the capecitabine dose we utilized is probably too high. The main toxicity is diarrhea, which is manageable with appropriate dose reductions.This combination may be preferable compared to a standard combination with infusional fluorouracil/leucovorin as it is more convenient and practical with similar efficacy. Thus, phase III trials are needed to clarify its role in the treatment of chemotherapy-na?ve advanced colorectal cancer patients.     

长春瑞滨联合卡培他滨治疗28例转移性乳腺癌

目的：观察长春瑞滨联合卡培他滨治疗转移性乳腺癌的疗效及安全性。方法：28例有可测量病灶的转移性乳腺癌患者，中心静脉持续滴注(Civ)长春瑞滨：6mg／m^2，第1—5天，21天为一个周期，同时联合卡培他滨治疗2—4个周期。所有患者既往均接受过1种以上化疗方案的治疗，其中19例接受过蒽环类和(或)紫杉类治疗。结果：28例患者中13例接受了2个周期化疗，15例完成4个周期的化疗。CR 1例(3．57％)，PR 6例(21．43％)，MR7例(25．0％)，SD7例(25．0％)，PD7例(25．0％)，有效率达50．0％。最常见的不良反应为中性粒细胞减少、手足综合症、神经毒性、皮肤色素沉着、乏力等。结论：长春瑞滨联合卡培他滨作为二线方案治疗转移性乳腺癌的疗效确切，且不良反应可以耐受。有望成为转移性乳腺痛的理想二线化疗方案。     

Efficacy and safety of camrelizumab plus chemotherapy versus chemotherapy alone in patients with untreated,HER2-negative,unresectable locally advanced,or metastatic gastric cancer or gastroesophageal junction cancer: a retrospective comparative cohort study

BackgroundNivolumab combined with chemotherapy has been shown to improve prognosis in patients with untreated, human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (GC) and programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥5. However, the available first-line treatment options for advanced GC are limited. Analysis of efficacy and safety of other programmed cell death protein 1 (PD-1) antibodies combined with chemotherapy may provide alternative treatment options.MethodsThis retrospective study included patients with untreated, HER2-negative, unresectable locally advanced, or metastatic GC or gastroesophageal junction (GEJ) cancer who received either camrelizumab combined with oxaliplatin plus S-1 (SOX)/capecitabine plus oxaliplatin (CapeOX) or SOX/CapOX alone between November 2020 and April 2022. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety were evaluated.ResultsThis study included 49 patients in camrelizumab plus chemotherapy group and 54 in chemotherapy group. The baseline clinical characteristics beyond Epstein-Barr virus (EBV) status and PD-L1 CPS had no difference between combination group and chemotherapy group. ORR and DCR were significantly higher in combination therapy group than in chemotherapy group (59.18% vs. 38.89%, P=0.048; 83.67% vs. 62.96%, P=0.018). The median PFS in combination group was significantly longer than chemotherapy group [10.03 vs. 6.24 months, hazard ratio (HR) 0.603, 95% confidence interval (CI): 0.368–0.989, P=0.045]. The OS was not mature at the time of the OS analysis, with 40% patients died. Subgroup analyses showed that PFS was longer in patients with PD-L1 CPS ≥1 compared with CPS <1 and in patients with a neutrophil-lymphocyte ratio (NLR) <2.38 compared with ≥2.38. The most common grade 3–4 treatment-related adverse events (TRAEs) were granulocytopenia (57% in combination group vs. 54% in chemotherapy group), anemia (39% vs. 33%, respectively), and thrombocytopenia (39% vs. 33%, respectively). The proportion of reactive cutaneous capillary endothelial proliferation (RCCEP, 73% vs. 0%) was higher in combination group relative to chemotherapy group; all were grades 1–2.ConclusionsAmong patients treated with camrelizumab combined with chemotherapy, the clinical outcomes were superior to those patients treated with chemotherapy. However, these promising findings need to be confirmed in future clinical trials.     

XELOX与FOLFOX6方案一线治疗晚期结直肠癌的近期疗效及不良反应比较

目的:比较卡培他滨(希罗达)联合奥沙利铂(XELOX)方案与亚叶酸钙、5-氟尿嘧啶(5-FU)联合奥沙利铂(FOLFOX6)方案一线治疗晚期转移性结、直肠癌的疗效和不良反应.方法: 将62例晚期结、直肠癌患者随机分为两组,XELOX方案组(n=31):卡培他滨(capecitabine,Xeloda)1000mg/m2,2次/d,口服,第1天至第14天;奥沙利铂(oxaliplatin)130mg/m2,静脉滴注,持续3h,第1天;21天为1周期.FOLFOX6方案组(n=31):亚叶酸钙(CF)200mg/m2,静脉滴注,第1天,5-FU前;5-FU 400mg/m2,静脉推注,第1天,2400mg/m2,静脉持续滴注46h;奥沙利铂100mg/m2,静脉滴注,持续3h,第1天;14天为1周期. 结果: XELOX组缓解率(RR)为48.4%,中位肿瘤进展时间(TTP)6.8个月;FOLFOX6组RR为51.6%,TTP为7.1个月;两组比较各项指标差异无统计学意义(P＞0.05).不良反应中XELOX组手足综合征发生率高于FOLFOX组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX6组.结论: XELOX 方案一线治疗晚期结、直肠癌有确切疗效,不良反应能耐受,与FOLFOX6方案相当,但XELOX方案用药更为方便,安全性更好.     

Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: A meta-analysis of published randomised trials

Background:Several studies have investigated the possible roleof the adjuvant chemotherapy after curative resection for gastric cancerfailing to show a clear indication; previous meta-analyses suggested smallsurvival benefit of adjuvant chemotherapy, but the statistical methods usedwere open to criticisms. Materials and methods:Randomised trials were identified by meansof Medline and CancerLit and by selecting references from relevant articles.Systematic review of all randomised clinical trials of adjuvant chemotherapyfor gastric cancer compared with surgery alone, published before January 2000,were considered. Pooling of data was performed using the fixed effect model.Death for any cause was the study endpoint. The hazard ratio and its95% confidence intervals (95% CI), derived according to themethod of Parmar, were the statistics chosen for summarising the relativebenefit of chemotherapyversuscontrol. Results:Overall 20 articles (21 comparisons) were considered foranalysis. Three studies used single agent chemotherapy, seven combination of5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU withoutanthracyclines. Information on 3658 patients, 2180 deaths, was collected.Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82,95% CI: 0.75–0.89, P < 0.001). Association ofAnthracyclines to 5-FU did not show a statistically significant improvementwhen compared with the effect of the other regimens. Conclusions:Chemotherapy produces a small survival benefit inpatients with curatively resected gastric cancer. However, taking into accountthe limitations of literature based meta-analyses, adjuvant chemotherapy isstill to be considered as an investigational approach.     

Phase I, dose-finding study of capecitabine in combination with docetaxel and epirubicin as first-line chemotherapy for advanced breast cancer.

PURPOSE: Capecitabine is an oral fluoropyrimidine with considerable activity and minimal myelosuppression and alopecia. This phase I study evaluated the addition of capecitabine to epirubicin/docetaxel combination therapy as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: Twenty-three female patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin and docetaxel (75 mg/m2 i.v. on day 1). RESULTS: The maximum tolerated dose of capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no grade 4 non-hematological events and grade 3 events other than alopecia were rare. Alopecia occurred in all patients and treatment cycles, and asthenia occurred in all patients and in 84% of treatment cycles. Other frequent adverse events included nausea, vomiting, fever, paresthesia and elevated transaminase levels. An objective response to treatment was observed in 91% (95% confidence interval 72% to 99%) of patients. CONCLUSIONS: The addition of capecitabine to docetaxel/epirubicin combination therapy provides a well-tolerated and active first-line chemotherapy regimen in patients with advanced breast cancer, and merits phase II/III evaluation.     

卡培他滨单药或联合方案治疗晚期乳腺癌的疗效和安全性

目的 探讨卡培他滨单药或联合方案治疗晚期乳腺癌的疗效和安全性.方法 376例晚期乳腺癌患者接受如下方案治疗:(1)卡培他滨+多西紫杉醇方案:卡培他滨1000 mg/m2,口服,2次/d,第1～ 14天;多西紫杉醇60 ～75 mg/m2,静脉滴注,第1天;21 d为1个周期.(2)卡培他滨+长春瑞滨方案:卡培他滨1000 mg/m2,口服,2次/d,第1～14天;长春瑞滨25 mg/m2,静脉滴注,第1、8天;21 d为1个周期.中位治疗3个周期.(3)卡培他滨单药方案:卡培他滨1000 mg/m2,口服,2次/d,第1 ～ 14天,21 d为1个周期.结果卡培他滨单药组患者的有效率(ORR)为12.8％,临床获益率( CBR)为21.6％.一线治疗患者的ORR( 14.8％)与二线或二线以上治疗患者的ORR (12.2％)差异无统计学意义(P＞0.05),但一线治疗患者的CBR( 35.2％)高于二线或二线以上治疗者(17.1％),差异有统计学意义(P＜0.01).卡培他滨联合多西紫杉醇组患者的ORR为53.8％,其中一线治疗患者的ORR(48.5％)与二线或二线以上治疗患者的ORR(57.4％)比较,差异无统计学意义(P＞0.05).卡培他滨联合长春瑞滨组患者的ORR为36.4％,其中一线治疗患者的ORR (60.0％)明显高于二线或二线以上治疗患者(16.7％),差异有统计学意义(P＜0.01).结论 卡培他滨单药或者含卡培他滨联合方案不仅可以用于晚期乳腺癌一线治疗,也是二线或二线以上治疗的有效选择方案,患者不良反应可耐受.联合化疗有效后序贯至单药可以进一步延长乳腺癌患者的治疗时间.