两种蒽环类化疗药物不良反应的对照分析

目的　观察分析临床两种常用蒽环类化疗药物的不良反应 ,为临床合理用药提供依据。方法　对照分析43例恶性肿瘤患者化疗过程中不良反应的发生情况。结果　脱发方面吡柔比星与阿霉素存在显著差异 ,消化道反应及骨髓抑制方面无统计学差异 ,由于累积剂量有限 ,所以心脏毒性方面未做分析。结论　患者对吡柔比星的耐受情况优于阿霉素 ,而且治疗组生活质量高于对照组     

Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III,HER2-positive breast cancer patients: a phase 2, open-label,multicenter, randomized trial

This trial was designed to compare the efficacy and safety between epirubicin (E) and carboplatin (C) in combination with paclitaxel (P) and trastuzumab (H) in neoadjuvant setting. In 13 Chinese cancer centers, 100 patients with HER2-positive, locally advanced breast cancer were 1:1 randomized to receive medication as follows: trastuzumab and paclitaxel weekly combined with carboplatin weekly for PCH group, or epirubicin every 3 weeks for PEH group. Patients were given 4 to 6 cycles of chemotherapy. The primary endpoint was pathologic complete response (pCR) rate, which was no significant difference in PCH and PEH regimen (39.1% vs. 48.8%; p=0.365). However, PEH regimen achieved higher pCR in luminal-B (HER2-poitive) subgroup (55.0% vs. 24.0%; p = 0.033), but not in ERBB2+ subgroup (42.9% vs. 57.1%; p = 0.355). PEH regimen showed a favorable efficacy in PIK3CA mutated subgroup (69.2% vs.23.5%, p=0.012). No significant difference was observed in the subgroup analysis of TP53 mutation status, PTEN expression, FCGR2A SNP and FCGR3A SNP. Both regimens as neoadjuvant chemotherapy achieve similar efficacy and safety. PEH might improve pCR rate, especially in the luminal-B subtype and PIK3CA mutation subtype. PEH is feasible and less likely to increase the incidence of acute cardiac events compared to PCH.     

Q-T间期离散度和心脏超声对蒽环类药物早期心肌损伤的预测价值

目的：探讨Q-T间期离散度和心脏超声对预测蒽环类药物引起的早期心肌损伤的敏感性及应用价值。方法入选29例乳腺癌患者,且均采用含蒽环类药物的方案化疗,应用表阿霉素剂量为75 mg /m2,进行2～6个周期,随化疗进行体内蒽环类药物累积剂量不同,动态监测心电图Q-T间期离散度及心脏超声变化,并进行分析与评价。结果化疗后Q-T间期离散度较化疗前明显延长,差异有显著性意义,P＜0．001。化疗后左室舒张末期前后径较化疗前轻度增大、左室射血分数较化疗前轻度下降,但差异无显著性意义, P＞0．05。结论化疗药物对心肌损伤的评价指标中,心电图Q-T间期离散度较心脏超声的左室舒张末期前后径和左室射血分数更为敏感,具有对蒽环类药物引起的心肌损伤的早期预测价值,通过监测心电图Q-T间期离散度变化,能及早在心肌损伤亚临床阶段发现其心脏毒性的发生与进展。     

三阴性乳腺癌TAC方案治疗及预后分析

 目的    研究三阴性乳腺癌(triple-negative breast cancer,TNBC)应用TAC化疗方案的疗效,并分析其影响因素。 方法    回顾性研究本院自2006年至2013年应用TAC化疗方案治疗的TNBC 87例,中位随访25个月,描述临床病例资料［年龄、月经状况、肿瘤体积、组织学分级、淋巴结转移、脉管侵犯、化疗不良反应、2年的无病生存期(disease free survival,DFS)及总生存期(overall survival,OS)等］,通过单因素及多因素分析方法分析生存预后的影响因素。 结果    87例TNBC绝经前45例(51.7%),绝经后42例(48.3%);平均肿瘤大小(2.90±1.68) cm (1.0~11.0cm),T1 35例(40.2%)、T2 45例(51.7%)、T3 7例 (8.0%);腋窝淋巴结转移率为41.4%,N0 51例(58.6%),N1 26例(29.9%),N2 7例(8.0%),N3 3例(3.4%);脉管侵犯率为25.3%;77例行全乳切除根治性手术(88.5%),9例行保乳术 (10.3%);77例行辅助化疗(88.5%),10例行新辅助化疗(11.5%);TAC化疗方案主要不良反应是中性粒细胞减少。复发转移9例,77.8%的复发转移为内脏脏器的转移,死亡5例。2年DFS为87%,2年OS为94%。单因素分析得出肿瘤大小、淋巴结分期、脉管侵犯、化疗方式均是DFS和OS的影响因素(P <0.05)。Cox回归多因素分析得出肿瘤大小是DFS的独立影响因素(P=0.003),肿瘤大于5 cm的复发转移风险是肿瘤小于2 cm的23.52倍,以上各因素均不是OS的独立影响因素(P >0.05)。 结论   TNBC早期远处转移率高,肿瘤体积大者易早期发生复发转移。除了淋巴结转移途径外,可能存在其他重要机制促使肿瘤发生早期远处转移。     

Phase II trial of menogaril in advanced colorectal cancer

Summary Menogaril, a new semisynthetic anthracycline antibiotic, was administered to 35 patients with advanced colorectal cancer. The drug was infused over 2 hr at a dose of 160 mg/sqm or 200 mg/sqm repeated every 4 weeks. Twenty-seven patients were evaluable for response and no objective responses were achieved. Myelosuppression, only leukopenia, was usually of mild-moderate degree and occurred in 63% of the patients. Twenty-seven percent of the patients experienced severe leukopenia. Local erythema and phlebitis were frequently observed and were severe in 13% of the patients. Nausea/vomiting (66%) and alopecia (50%) were of mild-moderate degree.This study suggests that menogaril at these doses and schedule had no activity in advanced colorectal cancer.for the EORTC Early Clinical Trials Group (EORTC/ECTG)     

The clinical benefit of pegylated liposomal doxorubicin in patients with metastatic breast cancer previously treated with conventional anthracyclines: a multicentre phase II trial

This study evaluates the clinical benefit of pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC), previously treated with conventional anthracyclines. Seventy-nine women with MBC previously treated with anthracyclines received PLD 50 mg m(-2) every 4 weeks. All patients were previously treated with chemotherapy and 30% of patients had > or =3 prior chemotherapies for metastatic disease. Patients were considered anthracycline resistant when they had disease progression on anthracycline therapy for MBC or within 6 months of adjuvant therapy. The overall clinical benefit rate (objective response+stable disease > or =24 weeks) was 24% (16.1% in patients with documented anthracycline resistance vs 29% in patients classified as having non-anthracycline-resistant disease). There was no difference with respect to the clinical benefit between patients who received PLD >12 months and those who received PLD < or =12 months since last anthracycline treatment for metastatic disease (clinical benefit 25 vs 24.1%, respectively). Median time to progression and overall survival were 3.6 and 12.3 months, respectively. The median duration of response was 12 months, and the median time to progression in patients with stable disease (any) was 9.5 months. Fourteen patients (17.7%) had a prolonged clinical benefit lasting > or =12 months. In conclusion, PLD was associated with an evident clinical benefit in anthracycline-pretreated patients with MBC.     

Novel anthracycline prodrugs

This paper highlights recent patents in the field of anthracycline prodrugs, which are employed in tumour-selective chemotherapy. The prodrugs can be a part of a two-step directed enzyme prodrug therapy (DEPT), which involves the localisation of the prodrug trigger at the tumour site, followed by the administration of the prodrug and subsequent tumour-selective anthracycline release. In most cases this trigger is an enzyme, which is indirectly localised by an antibody (ADEPT) or a gene encoding for an enzyme (GDEPT). Furthermore, anthracyclines can be targeted to the tumour site via prodrug monotherapy. Anthracycline prodrugs exploiting differences in physiological conditions, such as a lower pH and a lower oxygen tension in tumour tissue compared to healthy tissue, tumour-specific enzymes, such as plasmin, cathepsin B and β-glucuronidase are discussed. Finally, prodrugs are reviewed that home to tumour-selective receptors. Promising advances in this field concern receptors that are required for angiogenesis.     

Anthracycline‐based chemotherapy in metastatic endometrial carcinoma: An update

The purpose of this review is to analyze clinical evidence about the activity and efficacy of anthracycline‐based chemotherapy in metastatic endometrial cancer and to identify the most important preclinical findings that would address future clinical trials. A literature search of published studies was undertaken. Studies were selected by predefined criteria. Clinical trials and preclinical studies were analyzed. The search identified eight phase 3 and 13 phase 2 clinical trials of patients with metastatic endometrial carcinoma treated with an anthracycline‐based regimen. The planned dose intensity of the anthracycline had no effect on response rates and survival. Survival increased for patients with a good performance status, and sometimes the duration of responses to anthracycline monotherapy can be very long‐lasting. The major findings of anthracycline resistance in preclinical models are reported. Possible future biomarkers targeting mechanisms of anthracycline resistance are suggested, and efforts to define a molecular classification of endometrial cancer are desirable.