Chemotherapy-induced amenorrhea: influence on disease-free survival and overall survival in receptor-positive premenopausal early breast cancer patients.

BACKGROUND: The aim of this study was to evaluate the influence of early chemotherapy-induced amenorrhea (CIA) on disease-free survival and overall survival in premenopausal patients with receptor-positive early breast cancer treated with adjuvant chemotherapy without any hormonotherapy. PATIENTS AND METHODS: Retrospectively, we reviewed data from 130 premenopausal patients with localized hormone-sensitive breast cancer. These patients were treated between 1985 and 1995 at the same institution. They all underwent a loco-regional treatment and adjuvant chemotherapy. Early CIA was defined as an amenorrhea arising during the first year following the beginning of chemotherapy. Predictors of early CIA were examined. The survival analyses were done using the Kaplan-Meier method and Cox analysis. RESULTS: Median follow-up was 9 years. Mean age was 42.9 +/- 5 years. Ninety-two per cent of patients had histologically-proven positive axillary nodes. Adjuvant chemotherapy contained no anthracycline in 63%. Early CIA occurred during or after adjuvant chemotherapy in 57% of the patients. It was definitive in 91%. In our study, age was the only CIA predictor in univariate analysis. Women who experienced early CIA tend to have a longer disease-free survival, but the difference was not significant. This trend was lost in multivariate analysis, most probably due to the small sample size. The overall survival was not different. CONCLUSION: Although not statistically significant, our results on a very selected population of patients suggest that a chemotherapy-induced amenorrhea might have its own therapeutic effect besides the cytotoxic action of chemotherapy.     

Cost-effectiveness analysis of breast cancer adjuvant treatment: FEC 50 versus FEC 100 (FASG05 study).

BACKGROUND: The aim of the study was to assess the incremental cost-effectiveness ratio (ICER) of the FEC 100 compared with the FEC 50 in the FASG05 trial. MATERIALS AND METHODS: A cost-effectiveness analysis was performed using a multi-state Markov process model. Relevant clinical data introduced into the model were obtained from 10-year follow-up of the clinical trial FASG05. Survival curves for each health state were assessed by survival parametric model. The model allowed assessments from the start of adjuvant chemotherapy until death. The costs of adjuvant treatment and follow-up were estimated. The costs of recurrence were evaluated from the medical records of 146 patients. A prospective survey was performed on a cohort of 87 patients to quantify the resources external to the hospital (including cost of transportation). The inpatient costs were evaluated using the French diagnosis-related groups. The ambulatory costs were assessed using the French nomenclature. Costs were expressed in 2002 Euro (), according to the French societal perspective. The ICER assessed the cost of one additional life year saved. A discount rate of 5% per year was used for cost, and alternatively 0%, 3% and 5% for effectiveness. We validated the results with a probabilistic sensitivity analysis incorporating parametric and non-parametric bootstraps, and with the acceptability curves. RESULTS: The mean total discounting cost of adjuvant treatments was 11 465 for FEC 50 and 13 815 for FEC 100; the mean total discounting cost of recurrences was 14 636 and 13 503, respectively. According to the discount rate of effectiveness, the life expectancy was 16.5, 11.4 and 9.3 years for FEC 50 and 18.4, 12.5 and 10.2 years for FEC 100. The ICER (cost per life year saved) were 642, 1084 and 1460, respectively. The probability according to which FEC 50 is strictly dominated by FEC 100 was 0.15. CONCLUSION: The clinical benefit of FEC 100 generates a negligible cost increase when compared with FEC 50.     

Cost-effectiveness of new guidelines for adjuvant systemic therapy for patients with primary breast cancer.

BACKGROUND: In this study, the potential impact of a new national guideline for adjuvant systemic therapy in breast cancer (introduced in The Netherlands in 1998) was assessed, as well as the modifications of this guideline, issued in 2001. Both the change in total number of patients eligible for adjuvant therapy, as well as the cost-effectiveness of the changed clinical management of these patients were analysed. PATIENTS AND METHODS: Percentages of patients who would be eligible for adjuvant therapy in 1994, 1998 and 2001 were estimated, based on clinical data from 127 patients, who were operated on in 1994. Ten-year overall survival rates were used as a measure of effectiveness, based on the two most recent EBCTCG meta-analyses. Actual resource costs were calculated. With a decision analytic model, the incremental cost-effectiveness ratios (1998 versus 1994, and 2001 versus 1998) were calculated. RESULTS: The introduction of the 1998 guideline resulted in a relative increase of 80% in the total number of patients eligible for adjuvant therapy, compared with 1994 (from 40% to 72% of all patients with primary breast cancer). With an estimated absolute increase of 10-year overall survival of 2%, the 1998 guideline was found to have an expected incremental cost-effectiveness ratio of about 4837 per life-year gained. CONCLUSIONS: Introduction of the new guideline considerably affected the number of patients eligible for adjuvant systemic therapy for breast cancer. The associated incremental cost-effectiveness ratio is well within the range of values that are generally considered acceptable.     

IL-10与可溶性鸡Ⅱ型胶原对实验性关节炎的联合治疗作用

目的 :考察重组人白细胞介素 10 (rhIL 10 )对可溶性鸡Ⅱ型胶原 (SCCⅡ )治疗大鼠佐剂性关节炎(AA)疗效的影响。方法 :通过测量足肿胀度、体重、胸腺与脾脏系数 ,观察不同部位淋巴细胞ConA增殖反应并检测腹腔巨噬细胞 (PMΦ)与滑膜组织细胞(SMCs)产生IL 1的水平。结果 :与SCCⅡ(0 .0 3mg·kg-1·d-1,ig)或IL 10 (1,2 μg·d-1,sc)单独治疗比较 ,二者联合治疗大鼠AA ,明显改善上述观察指标 ,同时使SCCⅡ的口服耐受诱导期缩短 ,增强了治疗效果。结论 :IL 10能提高SCCⅡ治疗大鼠AA的治疗效果。     

军地融合共建新型医疗联合体探讨——以福建中医药大学附属第三人民医院为例

目的 探讨绝经前乳腺癌化疗致闭经(CIA)的影响因素,了解化疗后卵巢功能的变化规律及CIA与绝经的关系。 方法 回顾性收集300例接受化疗(至少4个周期)的绝经前乳腺癌的临床资料,记录患者的年龄、病理类型、肿块分期、腋窝淋巴结转移数、激素受体、人表皮生长因子受体-2(HER-2)、化疗方案、放疗、内分泌治疗、靶向治疗、月经变化等情况和血清性激素水平[卵泡剌激素(FSH),黄体生成素(LH),雌二醇(E2)]并进行分析。采用ROC曲线、Fisher精确概率检验及卡方检验分析各因素与CIA之间的关系。使用Kaplan-Meier生存分析统计CIA发生时间与性激素水平达到绝经时间的差异。 结果 204 例患者出现CIA,年龄与CIA发生具有明显相关性,曲线下面积为0.899(P<0.001,95%CI:0.863～0.935),年龄影响CIA的最佳临界值为43 岁。CIA的发生与病理类型、肿块分期、腋窝淋巴结转移数、雌激素受体(ER)、孕激素受(PR)、HER-2状态无关、化疗方案、是否放疗、曲妥珠单抗靶向治疗、内分泌治疗无关(P>0.05)。CIA患者中,年龄≤45 岁者更易恢复月经(91.4% vs 35.8%,P<0.001),月经恢复的中位时间为6.7 月(3.0～11.3 月); 绝经更多见于年龄>45 岁者(1.4% vs 50.0%,P<0.001)。Kaplan-Meier分析显示,CIA的发生时间明显早于性激素水平达到绝经的时间(2.6月 vs 13.6月,P<0.001); 在46～50岁、>50岁两个年龄组中,CIA均明显早于性激素水平达绝经的时间[(2.6月 vs 17.2月,P<0.001),(1.9月 vs 12.1月,P<0.001)]。 结论 年龄是CIA发生、月经恢复的独立且具有预测意义的重要影响因素。绝经多发生在确诊乳腺癌时年龄>45岁的患者,月经恢复多见于≤45岁患者。CIA的发生明显早于性激素水平达绝经状态,这一时间间隔对乳腺癌患者出现CIA后绝经状态的判断具有重要的参考价值,对合理选择内分泌治疗药物具有重要的临床意义。     

Noninterferon-based adjuvant therapy for high-risk melanoma

High-dose interferon is the only treatment approved by the FDA for adjuvant therapy of melanoma. However, its efficacy in this setting is questionable and its administration is associated with considerable toxicity. Many new agents are being tested clinically that hold the promise of greater efficacy and less toxicity but none of these have yet shown efficacy in controlled trials. These include biologics such as vaccines, cytokines, monoclonal antibodies, gene transfer, cellular therapies and angiogenesis inhibitors as well as chemotherapy combinations.     

Screening and appraisal for immunological adjuvant-active fractions from Platycodon grandiflorum total saponins

In this study, the total saponins from the root of Platycodon grandiflorum (PGS_t) was subjected to D101 macroreticular resin column chromatography to afford four fractions (PGS₃₀, PGS₅₀, PGS₇₅ and PGS₉₅). PGS_t and its four fractions were evaluated and compared for the haemolytic activities and adjuvant potentials on the specific cellular and humoral immune responses of ICR mice against recombinant hepatitis B surface antigen (HBsAg). PGS_t, PGS₃₀, PGS₅₀, PGS₇₅, and PGS₇₅ showed a slight haemolytic effect, with their concentration inducing 50% of the maximum haemolysis (HD₅₀) being 16.13?±?0.81, >200, 17.53?±?0.24, 20.16?±?0.76, 76.31?±?2.20?μg/mL against 0.5% rabbit red blood cell, respectively. PGS_t, PGS₅₀, and PGS₇₅ significantly not only enhanced the Con A-, lipopolysaccharide-, and HBsAg-induced splenocyte proliferation, but promoted the killing activities of natural killer (NK) cells from splenocytes in HBsAg-immunized mice (P?<?0.01 or P?<?0.001). HBsAg-specific IgG, IgG1, IgG2a, and IgG2b antibody levels in serum were also significantly enhanced by PGS_t, PGS₅₀, and PGS₇₅ compared with HBsAg control group (P?<?0.05, P?<?0.01, or P?<?0.001). Moreover, the adjuvant effects of PGS₅₀ and PGS₇₅ on the cellular immune responses and HBsAg-specific IgG2a and IgG2b antibody responses were more significant than those of Alum, PGS₃₀, and PGS₉₅. The results indicated that PGS₅₀ and PGS₇₅ could improve both cellular and humoral immune responses, and elicit a balanced Th1/Th2 response to HBsAg in mice, and that PGS₇₅ may be developed as an ideal candidate adjuvant for hepatitis B vaccine.     

Glucocorticoid and Starvation Effect on Glycosaminoglycans in Vascular Connective Tissue: Biochemical Studies on Repair Processes in Rabbit Aorta

Male rabbits were injured by a single mechanical dilatation injury of aorta and then injected with pred-nisone 2 mg/kg or saline for 14 days or subjected to starvation. The biosynthesis of the sulfated glycos-aminoglycans as evaluated by the uptake of ³⁵S-sulfate and the content of the glycosaminoglycans were measured on the intima-media layer of the descending thoracic aorta. The results indicate that prednisone may inhibit the biosynthesis of heparan and/or dermatan sulfate while starvation increases the biosynthesis of all the sulfated glycosaminoglycans. No alterations were observed in the total amount of glycosaminoglycans in aorta following glucocorticoid injection or starvation. The metabolism of aortic glycosaminoglycans during repair is less sensitive to the action of prednisone than in undamaged aorta2. This contrasts with the effect of prednisone on the metabolism of aortic collagen³.     

补体C3d-p28增强阿尔茨海默病DNA疫苗Th2型免疫反应的研究

目的 探讨补体C3d-p28作为分子佐剂,在阿尔茨海默病DNA疫苗免疫反应中的作用。方法 分别将重组质粒p(Aβ3-10)10,p(Aβ3-10)10-C3d-p28.3和空载体pc DNA3.1(+)用肌肉注射的方法免疫8~10周龄的雌性BALB/c鼠。质粒注射前24 h,布比卡因肌肉注射诱导轻微的肌肉变性。应用ELISA方法检测血清抗Aβ抗体的滴度、抗体分型、体外脾细胞培养上清液中IL-4和IFN-γ的含量。免疫组织化学染色法检测免疫血清与转基因鼠脑内Aβ斑的结合能力。结果 重组质粒疫苗p(Aβ3-10)10仅诱导出低滴度的抗Aβ抗体,产生了Th1/Th2混合型的免疫反应。而重组质粒疫苗p(Aβ3-10)10-C3d-p28.3诱导出较高滴度的抗Aβ抗体,体外脾细胞培养上清液中IFN-γ低和IL-4高,即引起了Th2型细胞免疫反应,同时产生的抗Aβ抗体能够与双转基因鼠APP/PS1脑中沉积的Aβ斑块结合。结论 补体C3d-p28分子佐剂能够增强抗Aβ抗体的产生并且诱发Th2型的免疫反应。