Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer).

BACKGROUND: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. PATIENTS AND METHODS: Women with stage III or IV breast cancer aged > or =70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m(2) was administered weekly for 3 weeks every 28 days. RESULTS: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5-18.7) and median survival was 35.8 months (95% CI 19-not defined). CONCLUSIONS: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherapy.     

紫杉醇耐药的研究进展

紫杉醇是继阿霉素和顺铂之后，又一新的具有良好抗癌效果的药物，它使多种肿瘤治疗的有效率得到了大幅度的提升，具有极高的开发利用价值。目前，紫杉醇被用于治疗各种类型的肿瘤，包括膀胱癌、乳腺癌、食道癌、胃癌、肺癌、卵巢癌和前列腺癌，但由于它耐药的产生极大地限制了其临床疗效。本文将对其耐药机制及相应研究做一小结。     

MiR-634 sensitizes nasopharyngeal carcinoma cells to paclitaxel and inhibits cell growth both in vitro and in vivo

Resistance to chemotherapy is one of the key causal factors in cancer death and increasing evidence has revealed that microRNAs (miRNAs) are involved in chemoresistance in many kinds of human cancers. Paclitaxel has been used for treatment of advanced nasopharyngeal carcinoma (NPC); however, treatment failure often occurs due to development of acquired paclitaxel resistance. In this study, based on miRNA microarray screening and qRT-PCR validation, we found six differentially expressed miRNAs in our induced paclitaxel-resistant NPC CNE-1/Taxol cells. Furthermore, we clarified the role of miR-634, most significantly downregulated in the paclitaxel-resistant CNE-1/Taxol, in regulating the paclitaxel sensitivity in NPC cells. We restored miR-634 expression in the CNE-1/Taxol cells by lentivirus infection, and found restoration of miR-634 re-sensitized the CNE-1/Taxol cells to paclitaxel in vitro by MTT assay and colony formation assay. In xenograft mouse model, we found that miR-634 inhibited tumor growth and enhanced paclitaxel sensitivity. Thus, our findings provide important information for the development of targeted gene therapy for reversing paclitaxel resistance in NPC.     

Copy number changes of 4-gene set may predict early relapse in advanced epithelial ovarian cancer after initial platinum-paclitaxel chemotherapy

For advanced epithelial ovarian cancer (EOC), time to recurrence (TTR) is an important indicator to gauge the therapeutic efficacy of postoperative adjuvant chemotherapy. Our objective was to determine the genes that could potentially distinguish patients with short versus long TTR after initial administration of platinum-paclitaxel combination chemotherapy in advanced EOC. Tumor samples of 159 patients were obtained during the primary cytoreduction. Array comparative genomic hybridization (CGH) was carried with genomic DNA from 17 EOC samples (8 with TTR > 15 months and 9 with TTR ≤ 6 months) to screen candidate gene set, copy-number changes (CNC) of which were significantly different between early and late relapse cases. Seventeen candidate genes were identified by array CGH. The analysis of consistency between real-time PCR and array CGH revealed that 4 genes displayed consistent results, namely GSTT1, ISG20L1, STARD5 and FREM1. In a 142-case validation set, CNC of 4 candidate genes was evaluated and verified by real-time PCR. Sixty five point five percent of the patients were correctly divided into early (TTR ≤ 10 months) and late (TTR > 10 months) recurrent group by CNC of the 4 genes using discriminant analysis. The results showed that CNC of 4-gene set could potentially determine early (TTR ≤ 10 months) or late relapse (TTR > 10 months) after initial platinum-paclitaxel combination chemotherapy in advanced EOC.     

Utilisation des ballons actifs dans l’angioplastie coronaire : indications actuelles et perspectives

The paclitaxel-eluting balloon is an emerging percutaneous coronary angioplasty tool which aim is to prevent restenosis by delivering a high intravessel paclitaxel dose during balloon inflation. It has been already approved in the treatment of bare metal stent restenosis and is being investigated in drug-eluting stent restenosis. For the treatment of de novo lesions, it could be used alone or in combination with bare metal stent implantation. Most interesting results were obtained by a drug-eluting balloon alone strategy in small vessels angioplasty. Current and upcoming results of this evolving technology are reviewed.     

乳腺癌Survivin表达意义及苦参临床疗效分析

目的:探讨乳腺癌（breast cancer，BC）Survivin表达与以紫杉醇为主的化疗疗效之间的关系，并进一步研究复方苦参注射液对化疗疗效的影响。方法:筛选119例乳腺癌患者，通过回顾性分析，依据既往用药情况分为:含紫杉醇化疗组（A组）和化疗联合复方苦参注射液组（B组）。应用免疫组化法检测患者肿瘤组织中Survivin表达水平，再分为阳性表达组和阴性表达组。分别以χ2检验和Kaplan-Meier方法分析有效率和生存时间的差异。结果:A组阴性表达患者化疗有效率为83.3%，明显高于阳性表达组（P=0.031）；且PFS、OS均较阳性组延长，但仅PFS差异具有统计学意义（P=0.046）。B组阳性表达与阴性表达者在化疗有效率、PFS、OS方面均无明显差异。两组之间比较发现:联合苦参B组阳性表达患者有效率较单纯化疗A组阳性表达者有明显升高趋势(P=0.026)。阳性表达者PFS在联合苦参后由12.761月提高到16.197月，具有统计学差异（P=0.027）。OS由30.789月提高到36.570月，但差异并没有统计学意义（P>0.05）。结论:对Survivin表达水平的检测有望成为乳腺癌含紫杉醇化疗方案的预测指标，且针对Survivin高表达患者联合复方苦参注射液可能提高化疗的有效率，甚至延长PFS。     

Nanotechnology for targeted cancer therapy

Cancer nanotechnology is currently under intense development for applications in cancer imaging, molecular diagnosis and targeted therapy. The basic rationale is that nanometer-sized particles, such as biodegradable micelles, semiconductor quantum dots and iron oxide nanocrystals, have functional or structural properties that are not available from either molecular or macroscopic agents. When linked with biotargeting ligands, such as monoclonal antibodies, peptides or small molecules, these nanoparticles are used to target malignant tumors with high affinity and specificity. In the ‘mesoscopic’ size range of 5–100 nm in diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to multifunctional nanoparticle probes for molecular and cellular imaging, nanoparticle drugs for targeted therapy, and integrated nanodevices for early cancer detection and screening. These developments have opened exciting opportunities for personalized oncology in which cancer detection, diagnosis and therapy are tailored to each individual’s molecular profile, and also for predictive oncology, in which genetic/molecular information is used to predict tumor development, progression and clinical outcome.     

Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer.     

Gemcitabine,paclitaxel, and oxaliplatin (GEMPOX) in the treatment of relapsed/refractory intracranial nongerminomatous germ cell tumors

Intracranial germ cell tumors (GCT) account for less than 5% of all central nervous system tumors in children in Western countries. Approximately 40% are nongerminomatous GCT (NGGCT). Despite correct treatment, 16% to 47% of the patients will relapse. There are no standard approaches in case of recurrence, and treatment in this situation remains a challenge. We report three patients diagnosed with relapsed intracranial NGGCT treated with gemcitabine, paclitaxel, and oxaliplatin, in whom the tumor showed a remarkable response with normalization of tumor markers.