紫杉类联合顺铂+氟尿嘧啶治疗局部晚期头颈部鳞癌效果的系统评价

目的系统评价紫杉类联合顺铂+氟尿嘧啶与顺铂+氟尿嘧啶比较治疗局部晚期头颈鳞癌的有效性和安全性。方法计算机检索h e Cochrane Library(2013年第1期)、PubMed、EMbase、Web of Science、CBM、CNKI、VIP和WanFang Data数据库,收集所有紫杉类联合顺铂+氟尿嘧啶与顺铂+氟尿嘧啶比较诱导化疗治疗局部晚期头颈鳞癌的随机对照试验(RCT),检索时限均从建库至2013年4月1日。由2位评价员按纳入与排除标准独立筛选文献、提取资料并评价质量后,采用RevMan 5.2软件进行Meta分析。结果共纳入7个RCT,2088例患者,其中紫杉类联合顺铂+氟尿嘧啶诱导化疗组(TPF组)1051例,顺铂+氟尿嘧啶诱导化疗组(PF组)1037例。Meta分析结果显示:TPF组与PF组在1年总生存率[RR=1.12,95%CI(1.02,1.23),P=0.02]、2年总生存率[RR=1.20,95%CI(1.11,1.29),P<0.00001]、3年总生存率[RR=1.18,95%CI(1.07,1.31),P=0.0007]、1年无进展生存率[RR=1.18,95%CI(1.08,1.28),P=0.0002]、2年无进展生存率[RR=1.20,95%CI(1.06,1.36),P=0.003]、3年无进展生存率[RR=1.48,95%CI(1.25,1.74),P<0.00001]、完全缓解率[RR=1.67,95%CI(1.26,2.23),P=0.0004]和总反应率[RR=1.18,95%CI(1.11,1.27),P<0.00001]方面差异均有统计学意义,TPF组均优于PF组。在不良反应方面,与PF相比,TPF组中性粒细胞减少症发生率[RR=1.42,95%CI(1.24,1.63),P<0.00001]、脱发发生率[RR=16.09,95%CI(4.59,56.38),P<0.0001]和中性粒细胞减少性发热发生率[RR=2.21,95%CI(1.29,3.80),P<0.004]更高。结论紫杉类联合顺铂+氟尿嘧啶诱导化疗治疗局部晚期头颈鳞癌具有较好的治疗效果,但不良反应较多。     

The best use of adjuvant chemotherapy: New drugs and new use of “old” drugs

Modern chemotherapy has diminished the risks of distant relapse and death in many subgroups of patients with early stage breast cancer. Although the initial trials relied on empirically designed regimens, studies are increasingly based on preclinical science and reflect the growing understanding of the molecular basis of cancer. Empiric clinical trials proved the worth of combination chemotherapy, the limited value of very long courses of treatment, and the benefits of adding first anthracyclines and then later taxanes. More recent trials have demonstrated the limits on empiric dose escalation and the benefits of optimized scheduling. Many trials are currently focused on novel targeted agents. Based on several decades of studies in thousands of women it is reasonable to consider a combination of chemotherapy agents for patients with hormone unresponsive or otherwise high-risk tumors. Anthracyclines and taxanes should be incorporated into the treatment plans of patients in the higher risk subsets and the specific regimens should be taken from the several randomized studies. When available, eligible patients should be enrolled on prospective clinical trials.     

Advances in Breast Oncology: The 2002 ASCO Meeting

Summary

At this year's American Society of Clinical Oncology (ASCO) meeting, a number of important advances in breast cancer diagnosis, treatment and prevention were reported. In this article, we review these current developments, focusing particularly on the ASCO technology assessment report - which discussed the adjuvant use of aromatase inhibitors in breast cancer - and other significant studies which were presented or updated: the role of taxanes in neoadjuvant and adjuvant therapy; current

concepts regarding the timing of hormonal therapy during adjuvant chemotherapy; and cyclooxygenase-2 (COX-2) as a target for disruption in breast cancer treatment and prevention. With regards to advances in surgery, we review studies which were presented concerning the evolving role of sentinel lymph node biopsy in the management of the axilla in breast cancer, and review the latest meta-analysis on this subject presented at the meeting.     

Anti-tumour activity of a panel of taxanes toward a cellular model of human cervical cancer

Using a model of human cervical cancer (ME-180 cells), the anti-tumour activity of paclitaxel was compared to that of docetaxel and IDN5109, a newly developed taxane. The growth inhibition effect of taxanes was assessed after 3 days of exposure. DNA analysis, the taxane-dependent modulation of the expression of the α and β subunits of tubulin and DNA fragmentation were assessed by flow cytometry. The presence of apoptosis was confirmed by morphological analysis using a laser scan cytometer. For the evaluation of “in vivo” anti-tumour activity, taxanes were administered to nude mice intravenously once daily, according to a q3/4d × 4 schedule. Docetaxel, IDN5109 and paclitaxel obtained “in vitro” IC₅₀ values of 0.86, 1.4 and 2.4 nM, respectively. DNA analysis demonstrated a transient block at the G₂/M phase of the cell cycle only after 12 h of culture in the presence of taxanes and an increase of nuclear fragmentation suggestive for apoptosis after additional 12 and 60 h of exposure. Morphological analysis confirmed the presence of apoptosis. Taxanes induced a down-modulation of the α subunit of tubulin in the G_0/1 phase of the cell cycle, and an overexpression of the β subunit in the G₂/M phase. A strong anti-tumour activity was obtained “in vivo” for nude mice xenografted using ME-180 cells (T/C=0% for all drugs). These data indicate that the three taxanes are strongly active both “in vitro” and “in vivo” toward ME-180 cells. Clinical studies are now needed to ascertain if the higher anti-tumour activity observed “in vitro” using docetaxel and IDN5109 yields a better clinical response in advanced cervical carcinoma with respect to paclitaxel. Received: 4 May 1999 / Accepted: 9 July 1999     

Cost-effectiveness analysis of adjuvant therapy for node positive breast cancer in Korea: docetaxel, doxorubicin and cyclophosphamide (TAC) versus fluorouracil, doxorubicin and cyclophosphamide (FAC)

Background This study evaluated the incremental cost–effectiveness (ICER) and cost–utility ratios (ICUR) of TAC compared with FAC following primary surgery for node positive breast cancer patients in Korea. Materials and methods A cost–effectiveness analysis was performed using the Markov model from the combined view of Korean National Health Insurance and patients. The model allowed assessment from the beginning of the first cycle of adjuvant chemotherapy following primary surgery until death. Relevant clinical data were obtained from the clinical trial BCIRG 001 and data for local treatment patterns and direct medical costs were obtained from three Korean hospitals. Results Over a life time horizon, the life expectancy of TAC was 0.9 years longer than that of FAC. The ICER was 8,025,879 Korean won (KW, €6,573) per life year gained and the ICUR was 8,885,794 KW (€7,277) per QALY gained when the cost and effectiveness were discounted at 5%. The model was most sensitive to the percent patient receiving prophylactic granulocyte colony stimulating factor (G-CSF) in TAC arm and the ICUR was 12,119,561 KW (€9,926) when assuming 100%. Conclusions TAC appears to be cost–effective in the management of early breast cancer in Korea. An invited commentary to this article can be found at doi:.     

Systemic chemotherapy in locally advanced and/or metastatic bladder cancer

Transitional cell carcinoma of the bladder is a common malignancy. Advanced urothelial cancer is a chemosenstive neoplasm. Whereas the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was long-considered the standard of care for patients with advanced disease, the evaluation of newer agents with retained activity and improved tolerability has been the focus of much investigation over the past decade. Combinations such as cisplatin-gemcitabine (GC) and intensified, G-CSF supported MVAC have shown more favourable toxicity profile and equal or even improved efficacy. Specific groups of patients (elderly, patients with renal dysfunction or poor performance status or co-morbidities) who cannot tolerate cisplatin-based therapy, should receive carboplatin, gemcitabine or taxane-based treatment. Continuing improvements in our understanding of the molecular phenotype of individual patient tumors may lead to the appropriate therapies that target molecular aberrations unique to this malignancy. This review will summarize recent developments in the management of locally advanced (T4b, N 2-3) and/or metastatic (M1) bladder cancer.     

Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer

Purpose. To determine the association of phosphorylated/activated HER2 (P-HER2) and response to taxane chemotherapy in patients with metastatic breast cancer (MBC). Materials and Methods. Archived tumor specimens of patients with MBC treated on clinical trials with taxane monotherapy were analyzed by immunohistochemistry (IHC) for the presence of phosphorylated HER2 using the PN2A monoclonal antibody. Chi-squared analysis was performed to evaluate the association of P-HER2 status and efficacy of single agent taxane therapy. Results. One hundred twenty-six cases were identified as evaluable for both IHC and clinical outcome. Twelve cases (10 percent) were positive for P-HER2, of which 5 had evidence of clinical progression and 7 had evidence of clinical benefit with taxane therapy. Of the 114 cases that were negative for P-HER2, 20 demonstrated progression and 94 had clinical benefit. Chi-squared analysis revealed a significant correlation between the presence of P-HER2 and resistance to taxane therapy, χ² = 3.9724 and p = 0.046. Conclusions. Phosphorylated/activated HER2 is associated with clinical resistance to single agent taxane therapy for MBC. The likelihood of direct progression of disease on taxane was greater in cases of PN2A-positive tumors (42 percent) as opposed to PN2A-negative ones (18 percent, p = 0.046). Functional assessment of HER2 status may provide unique predictive information not seen with conventional assessments.     

3D QSAR studies for the beta-tubulin binding site of microtubule-stabilizing anticancer agents (MSAAs): a pseudoreceptor model for taxanes based on the experimental structure of tubulin

The antimitotic agent paclitaxel continues to play an important role in the cancer chemotherapy. However, its inefficacy on certain resistant cells and toxic side effects have led to the search of new taxanes with improved biological activity. By means of a pseudoreceptor modeling approach, we have developed a binding site model for a series of taxanes. It is the first 3D QSAR model derived from the experimentally determined tubulin structure obtained by electron crystallography studies. The model is able to correlate quantitatively the structural properties of the studied compounds with their biological data.     

3D QSAR studies of the interaction between beta-tubulin and microtubule stabilizing antimitotic agents (MSAA). A combined pharmacophore generation and pseudoreceptor modeling approach applied to taxanes and epothilones

Based on the conformer of paclitaxel extracted from the experimental tubulin structure, a pharmacophoric model has been generated and used to find the chemical features common to the taxane and epothilone classes of compounds. This original alignment has been translated into the experimental tubulin binding site obtaining an assembly subsequently submitted to the pseudoreceptor modeling approach. As a result, an original 3D QSAR model, able to evaluate, at a quantitative level, the relationships between the molecular structures and biological data of the studied compounds, has been obtained.