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.     

Other uses of dexrazoxane: savene,the first proven antidote against anthracycline extravasation injuries

Dexrazoxane has been in clinical use for more than 25 years for prevention of cardiotoxicity in anthracycline based anticancer therapy. However, we discovered another property of the compound, i.e. the ability to prevent the devastating tissue necrosis after accidental extravasation of anthracyclines. The preclinical and clinical studies leading to the clinical implementation of Savene™ (dexrazoxane) as the first and only proven antidote in anthracycline extravasation are described in short.     

心肌背向散射积分参数评价蒽环类抗肿瘤药心脏毒性的临床研究

目的 :探讨背向散射积分参数分析技术在评价蒽环类抗肿瘤药 (ATC)心脏毒性方面的应用价值。方法 :应用 HP Sonos550 0型超声诊断仪及其配置的背向散射联机分析软件测定 83例接受 ATC化疗的肿瘤患者及 50例正常对照组心肌背向散射积分参数 :心肌背向散射积分均值 (IBS) ;背向散射积分的心动周期变化幅度 (CVIB) ;心肌校正的背向散射积分均值 (IBS% )和背向散射积分周期变异率 (CVIB% )。结果 :ATC化疗组与对照组心肌 IBS均呈周期性变化 ,但 ATC化疗组变化幅度明显减低 ;ATC化疗组心肌 IBS%较对照组明显增高 (P<0 .0 5) ,CVIB和 CVIB%则较对照组明显减低 (P<0 .0 5,P<0 .0 1) ;ATC化疗组中 3 0例 (3 6.1% )患者出现左心室舒张功能指标异常 ,其中 E/A明显低于对照组。但左心室收缩功能参数和室间隔 (IVS)及左室后壁 (L VPW)的室壁增厚率 (Δ T% )在 ATC化疗组和对照组之间无显著性差异 ;IBS参数与 ATC累积剂量、距首次化疗时间、心功能参数及相应节段的室壁增厚率均无显著相关性。结论 :ATC化疗组患者心肌组织背向散射积分参数与对照组显著不同 ,背向散射积分参数测定可作为评价 ATC早期心脏毒性的手段之一。     

蒽环类药物对肿瘤患者左心功能影响的组织多普勒评价

目的探讨组织多普勒技术(TDI)在评价蒽环类药物(ATC)对肿瘤患者左心功能早期损害的临床应用价值。方法测定并比较26例肿瘤患者ATC化疗前和化疗后6个月的常规超声心动图参数及TDI参数。结果TDI显示ATC化疗后二尖瓣环的收缩期运动速度峰值(Sm)及舒张早期运动速度峰值(Em)较化疗前明显降低(P<0.05),心房收缩期运动速度峰值(Am)较化疗前明显升高(P<0.01),Em/Am较化疗前明显降低(P<0.01),但舒张早期左室充盈峰速度(E)、心房收缩期左室充盈峰速度(A)、E/A、E峰减速时间(DT)、左室等容舒张时间(IVRT)及射血分数(EF)、短轴缩短率(FS)等常规心功能指标化疗前后差异无显著性(P>0.05)。结论TDI技术能更早、更敏感地评价ATC对肿瘤患者左室功能损害。     

组织速度成像对蒽环类药物心脏毒性的评价

目的探讨利用组织多普勒定量组织速度成像QTVI技术对蒽环类药物早期心脏毒性进行评估。方法30例在江北人民医院化疗的肿瘤患者,所用化疗方案以表阿霉素（Epi）为主,表阿霉素总累计量（450±75）mg／m^2,每个疗程治疗前进行组织多普勒定量组织速度成像和常规超声心动图检查。同时设健康对照组20例。常规超声心动图指标包括左室舒张末内径（LVDd）,左室收缩末内径（LVDs）,左室射血分数（LVEF）,室间隔与左室后壁厚度（IVSTd、LVP．WTd）,二尖瓣口血流速度（早期速度E、晚期速度A及两者比值E／A）;定量组织速度成像测量二尖瓣环上左室侧壁及后间隔两个位点的峰值速度（收缩期峰值Vs、收缩期加速度a,舒张期峰值Ve）。结果与第一次治疗前对比,常规超声指标LVDd、LVDs、IVSTd、LVPWTd差别无统计学意义（P〉0．05）,左室射血分数在累积量达到450mg／m^2时差别有统计学意义（50．1±7．3与68．0±9．0,P〈0．05）。舒张期指标E／A在累积量达到375mg／m^2时差别有统计学意义（0．71±0．14与1．20±0．21,P〈0．05）。利用组织多普勒QTVI技术检测对比发现,收缩期指标Vs、a在累积量达300mg／m^2时差别有统计学意义[（5．70±1．07）cm／s与（7．84±1．10）cm／s、（132±14）cm／s^2与（219±31）cm／s^2,P〈0．05],舒张期指标Ve在累积量达到225mg／m^2差别有统计学意义[（6．86±1．04）cm／s与（8．74±1．32）cm／s,P〈0．05]。结论在监测表阿霉素心脏毒性上,组织多普勒超声心动图较常规超声心动图能较早期和较敏感发现心脏损害,且舒张功能的损害早于收缩功能。     

Docetaxel and epirubicin salvage regimen in relapsed anthracycline-sensitive metastatic breast cancer patients after anthracycline-containing adjuvant therapy

Summary  Our aim in this paper is to verify the efficacy and safety of a epirubicin and docetaxel salvage regimen for anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy. Thirty-two metastatic breast cancer patients were treated with epirubicin and docetaxel every 21 days. Of the 31 evaluable patients, there were 13/31 (41.9%) partial responses and no complete responses. Median time to progression was 12 months (95% CI, 4–60 months) and median survival duration was 41 months (95% CI, 1.2–80.8 months). According to the Cox model, ECOG performance and response group were statistically significant variables, and visceral metastasis was a borderline significant variable with regards to overall survival. Although this salvage regimen showed a high rate of hematologic toxicities, it was a relatively active regimen with manageable toxicities and no cardiac dysfunction. We propose that this salvage regimen could be carefully used in anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy.     

Sequential taxane and anthracycline-containing neoadjuvant regimens: The sequential order impact

Background

One can consider as a standard neoadjuvant treatment for breast cancer, the sequence of 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel. Based on the belief that the sequence order between anthracycline and taxane might be of interest, this study assessed the impact of the sequence order.

Methods

One hundred and twenty three patients with breast cancer were treated with neoadjuvant chemotherapy in 5 oncologic centers between 2003 and 2007. This study compared 65 patients treated with 4 cycles of docetaxel followed by 4 cycles of anthracycline-based chemotherapy (cohort T), versus another cohort of 58 patients treated with 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (cohort A).

Results

The overall dose intensity of docetaxel and clinical complete responses were significantly higher in cohort T. No statistically significant differences were observed in terms of conservative surgeries or histological responses. The sequence of chemotherapy did not significantly influence other treatment-related toxicities. Mild neurotoxicity was higher in patients treated in cohort T. Anemias (≥Grade 1) were higher in cohort A (52% versus 81%; p = 0.0008).

Conclusion

The present study failed to identify an impact of the sequence of taxane administration on the efficacy. Nevertheless, starting neoadjuvant chemotherapy by taxane reduces the occurrence of anemia. These findings might allow a selection of the sequence order based on the toxicity profile.