高剂量表阿霉素治疗非小细胞肺癌的随机研究

目的：观察以高剂量表阿霉素联合方案治疗非小细胞肺癌（NSCLC）的疗效和毒副反应。方法：每个病人给予两周期的EVpP方案治疗,每个周期表阿霉素（Eqinubicin)55mg/m2,cl1,2或d1,14;Vp16 100mg/d,d1-4,DDP 80mg/m2,d1。结果：可评价疗效20例患者中10例有效（PR）,总有效率50．0％,主要毒副反应为骨髓抑制,脱发,呕吐,口腔炎,结论：高剂量表阿霉素为主的联合化疗方案是治疗非小细胞肺癌有效的方案。     

Identification of the highest dose of docetaxel associable with active doses of epirubicin. Results from a dose-finding study in advanced breast cancer patients

Purpose:To determine the maximum tolerated dose (MTD) and thedose limiting toxicity (DLT) of docetaxel in combination with fixed doses ofepirubicin. Patients and methods:Women with locally advanced or metastaticbreast cancer were given docetaxel, 60 mg/m² in escalated doses bysteps of 10 mg/m², in association with two fixed doses ofepirubicin (90 mg/m², and 75 mg/m²). Since neutropeniawas foreseen to be the most likely DLT, a third group with prophylactic G-CSFsupport was planned to define the MTD of docetaxel with 90 mg/m²of epirubicin. Selected patients underwent pharmacokinetic evaluation ofdocetaxel. Results:Fifty-eight patients entered the study. At the first step(90 mg/m² of epirubicin) the MTD was obtained at 60mg/m² of docetaxel. At the second step (75 mg/m² ofepirubicin) the MTD of docetaxel was 80 mg/m². At the third step(epirubicin 90 mg/m²) G-CSF allowed a safe escalation of docetaxelup to 90 mg/m². Neutropenia was the most common hematologicaladverse event. Without G-CSF, grade 4 neutropenia occurred in 69% ofcycles, of which 11% was complicated by fever. In G-CSF group, grade4 neutropenia and neutropenic fever occurred in 31% and 3%,respectively. Most frequent non-hematological adverse effects were asthenia(45%), nausea (39%) and mucositis (36%). No patientdeveloped congestive heart failure. Two toxic deaths occurred. Overallresponse rate was 73% in 42 out of 58 patients, with no apparentepirubicin dose-related effect. No statistically significant effect of the twodoses of epirubicin was observed in docetaxel pharmacokinetics. Conclusions:On the basis of the toxicity profile, the docetaxelpharmacokinetics and the response rate observed, epirubicin 75mg/m² combined with docetaxel 80 mg/m² can berecommended for further studies.     

腺病毒介导IL-24联合化疗药物增强对肝癌细胞PLC/PRF/5增殖的抑制

目的：研究腺病毒介导IL-24基因（Ad.IL-24）与化疗药物联用对肝癌细胞株PLC/PRF/5增殖的抑制作用。方法：用Ad.IL-24分别联合化疗药物氟尿嘧啶（fluorouracil,5-Fu）和表柔比星（epirubicin,EPI）处理培养的肝癌细胞株PLC/PRF/5,MTT法检测细胞增殖抑制率,流式细胞术（FCM）检测细胞周期和凋亡率。结果：10 MOI Ad.IL-24与25μg/ml5-Fu联合应用后72h,PLC/PRF/5细胞增殖抑制率达（67.4±0.58）%,显著高于单用Ad.IL-24组的（46.8±0.74）%和5-Fu组的（29.3±0.60）%（均P〈0.05）;10MOIAd.IL-24与2.5μg/mlEPI联合应用后72h,PLC/PRF/5细胞增殖抑制率达（72.5±0.92）%,显著高于单用Ad.IL-24组的（46.8±0.74）%和EPI组的（32.2±0.69）%（均P〈0.05）。流式细胞术检测结果显示,Ad.IL-24与5-Fu或EPI联合应用明显导致细胞在G2/M期阻滞;Ad.IL-24＋5-Fu组细胞凋亡率为（52.15±2.32）%,显著高于单用Ad.IL-24组的（28.36±3.49）%和5-Fu组的（8.27±2.61）%（均P〈0.05）;Ad.IL-24＋EPI组细胞凋亡率为（58.67±1.73）%,显著高于单用Ad.IL-24组的（28.36±3.49）%和EPI组的（11.82±1.91）%（均P〈0.05）。结论：Ad.IL-24与5-Fu或EPI联用能显著提高对肝癌细胞株PLC/PRF/5增殖的抑制作用。     

晚期乳腺癌联合化疗的临床观察

目的 观察紫杉醇联合表阿霉素（TE方案）及诺维本联合表阿霉素（NE方案）治疗晚期乳腺癌的临床疗效和不良反应。方法 对120例晚期乳腺癌患者随机分为TE组58例和NE组62例，分别进行治疗观察。结果 TE组总有效率（65.5 %）和复治有效率（61.8 %）高于NE组（38.7 %和27.8 %），中位疾病进展时间长于NE组（P＜0.05）；两组初治有效率和中位生存期无显著差异（P＞0.05）；不良反应以骨髓抑制、胃肠反应和脱发为主，两组无显著差异性；NE组静脉炎、TE组关节肌肉酸痛的发生率相对高，但均可耐受。结论 紫杉醇联合表阿霉素和诺维本联合表阿霉素对晚期乳腺癌均有较好疗效，但TE组对复治患者疗效更好，可作为复治的晚期乳腺癌患者首选化疗方案。     

Sensitization of human renal cell carcinoma cell lines to TRAIL-induced apoptosis by anthracyclines

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new member of the tumor necrosis factor family. The present study investigated whether anthracyclines enhance TRAIL-induced apoptosis and cytotoxicity in renal cell carcinoma (RCC) cells. METHODS: Cytotoxicity was measured using the microtiter assay. Apoptosis was monitored using DNA ladder analysis. Caspase activity was determined using a quantitative colorimetric assay. RESULTS: Treatment of ACHN and Caki-1 human RCC lines with TRAIL, in combination with subtoxic concentrations of epirubicin (EPI) or pirarubicin (THP), enhanced induction of apoptosis and cytotoxicity. Sequential treatment with EPI followed by TRAIL induced significantly more cytotoxicity than the inverse treatment. The combined cytotoxicity of TRAIL and EPI was significantly inhibited by the TRAIL-neutralizing fusion protein DR5:Fc, although EPI did not affect the mRNA expression of DR4, DR5, DcR1 or DcR2. The combination treatment with TRAIL and EPI activated caspase-6 and -3, which were downstream molecules of the death receptor. Furthermore, the combined cytotoxicity of TRAIL and EPI was almost completely inhibited by Z-VAD-FMK, and partly inhibited by Ac-DMQD-CHO. CONCLUSION: These findings indicate that anthracyclines sensitize RCC cells to TRAIL-induced apoptosis and cytotoxicity through activation of caspases, suggesting that TRAIL, in combination with anthracyclines, has a therapeutic potential in the treatment of RCC.     

Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer – Results from the prospective German TMK cohort study

Data on treatment and outcome of advanced breast cancer in routine practice are rare, especially concerning recurrent disease, but important to complement the results from clinical trials and to improve the standard of care. We present data on choice of systemic first-line treatment, number of treatment lines, and survival of patients treated by medical oncologists in Germany.1395 patients recruited by 124 sites at start of first-line therapy into the ongoing, prospective German clinical cohort study TMK (Tumour Registry Breast Cancer) between February 2007 and October 2015 were analysed.The median OS was 33.8 months (95% CI 30.2–40.2) for HR-positive/HER2-negative, 38.2 months (95% CI 31.3–43.0) for HER2-positive and 16.8 months (95% CI 11.5–22.0) for triple negative breast cancer. Patients with triple negative tumours more often died before start of a third-line therapy than patients with HR-positive or HER2-positive tumours (44% vs. 25%). Use of taxane-based chemotherapies has increased since 2007, with 65% of all first-line chemotherapy-treatments containing taxanes in 2013–15 (60% HR-positive/HER2-negative, 75% HER2-positive, 56% triple negative). 52% of the patients with HR-positive/HER2-negative tumours received first-line endocrine therapy in 2013–15; when restricted to patients with only non-visceral metastases this percentage increased to 63%.To our knowledge, this is the first cohort study showing systemic first-line therapy for all subtypes of advanced breast cancer. Overall survival in the TMK is comparable to that reported by clinical trials despite the inclusion of older and comorbid patients.     

Phase II study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as first-line therapy in patients with non-resectable gastric cancer

Epirubicin, cisplatin and continuous infusion of 5-FU is a widely used palliative regimen in patients with gastric cancer. If cisplatin is substituted by oxaliplatin and 5-FU by capecitabine this regimen can be administered in the outpatient setting. Dose-limiting toxicity of oxaliplatin is peripheral sensory neuropathy and it is recommended to give oxaliplatin as a 120 min infusion. However, in patients with colorectal cancer a 30 min infusion of oxaliplatin can safely be administered without increasing neurotoxicity, standard infusion time is 30 min at our departments. In our phase I study the recommended doses of EXE was established (Dupont et al, 2006). Patients with non-resectable gastric adenocarcinoma were eligible. Patients received EXE (epirubicin 50 mg m⁻² day 1; capecitabine 1000 mg m⁻² day⁻¹ continuously and oxaliplatin 130 mg m⁻² day 1) as outpatient therapy every third week for a maximum of 8 cycles. From June 2004 to September 2005, we enroled 54 patients. Median age was 60 years (31–74 years) Median number of courses was 6 (1–8). Response rate was 45%. Median PFS was 6.8 (5.2–7.9) months and median survival was 10.1 (7.9–11.1) months. Most important grade 3 toxicities were as follows: nausea, vomiting, and diarrhoea (6%). Neurotoxicity grade 2 was seen in 36.5%. We therefore conclude, that EXE every third week is a convenient regimen that easily can be administrated in the outpatient setting but the regimen needs further evaluation in a phase III study.     

Effect of therapeutic concentrations of anthracyclines on monocyte phagocytosis of yeast cells

Summary The effect of therapeutic concentrations of doxorubicin, epirubicin, and mitoxanthrone on mature leukocyte function has been examined by measuring phagocytosis of yeast cells by surface-bound monocytes, using a fluorescence-quenching method. There was a 10% inhibition of monocyte phagocytosis by doxorubicin, but epirubicin and mitoxanthrone had no effect on monocyte phagocytosis. Anthracyclines may have a major immunosuppressive effect due to bone marrow depression. The lack of interference with mature monocyte function by epirubicin and mitoxanthrone provides a potential advantage in comparison with the parent compounds.     

Low Dose Intermittent 5-Fluorouracil,Epirubicin and Cyclophosphamide (FEC) in Poor Risk Patients with Advanced Transitional Cell Bladder Cancer: a Pilot Study

Summary

Fifteen patients with locally advanced or metastatic bladder carcinoma and with cardiac and/or renal impairment were treated with a combination of 5-fluorouracil, 400 mg/m², epirubicin, 40 mg/m², and cyclophosphamide, 400 mg/m². No complete or partial remissions were observed among the 14 evaluable patients. The toxicity level was very low. We are now trying to «tailor» platinum-based combinations to renal function.