Pharmacotherapy of endometrial cancer

Background: Endometrial cancer is the seventh most common malignancy among women worldwide. Despite most cases being diagnosed at an early stage, the death rate has increased steadily over the past 20 years. The lack of an effective, standardized adjuvant treatment for women at a high risk of recurrence has contributed to these disappointing results. Objectives: The goal of this review was to assess the role of hormonal and cytotoxic therapies in the adjuvant treatment of endometrial cancer. Once defined, an evidence-based management algorithm for this neoplasm was proposed. Methods: A thorough literature search was undertaken using the Cochrane and Pubmed databases. Systematic reviews, meta-analyses, and randomized controlled trials were first collected and critically analyzed. Other study types were secondarily considered when pertinent. Conclusions: The choice of the adjuvant therapy in early-stage endometrial cancer must be a patient-specific decision. Preliminary data suggest a role for chemotherapy in high-risk subgroups. However, further research is necessary to confirm this. To date, hormonal therapy has not been widely used in the management of early-stage disease, other than for conservative treatment in a fertility-sparing setting. Both hormonal and chemotherapy represent valuable therapeutic tools for the management of patients affected by advanced disease.     

两组新辅助化疗方案对局部晚期宫颈癌的临床疗效比较

目的探讨局部动脉介入栓塞化疗与静脉化疗治疗局部晚期宫颈癌的疗效比较。方法选取我科30例确诊为局部晚期宫颈癌患者,按照FIGO分期,Ib期12例,IIa期8例,IIb期10例。随机分两组,A组(动脉介入栓塞化疗)16例,B组(静脉化疗)14例。每例按剂量个体化进行化疗,均最多进行两疗程。比较两组疗效、不良反应及手术结果。结果 A组完全缓解5例(31.3%),部分缓解9例(56.2%),无缓解2例(12.5%);B组完全缓解2例(14.2%),部分缓解4例(28.5%),无缓解8例(57.1%),有显著统计学差异。A组不良反应较B组轻,有统计学差异。结论动脉介入栓塞化疗治疗局部晚期宫颈癌患者疗效优于静脉化疗,不良反应发生率低,在患者经济条件允许前提下值得在临床推广。     

Pharmacotherapy of head and neck cancer

Introduction: There are over 55,000 new cases of head and neck cancer diagnosed annually in the United States. Historically surgical resection was the standard of care, but due to vital structures in the head and neck region this led to severe morbidity. The integration of pharmacotherapy has rapidly expanded over the years into a multimodality treatment paradigm for locally advanced head and neck cancer, allowing organ-sparing treatment approaches. Here we discuss the various approaches and settings in which chemotherapy can be incorporated into the management of head and neck squamous cell carcinoma (HNSCC).

Areas covered: Chemotherapy in HNSCC can be administered in several different treatment circumstances: in the metastatic setting for palliation of symptoms and prolongation of survival, before definitive local treatment (induction), as part of definitive treatment simultaneously with radiation (concurrent) or after definitive local therapy (adjuvant).

Expert opinion: The incorporation of chemotherapy into the management of patients with head and neck cancer has allowed organ preservation approaches and improved survival. Because of the toxicities of chemotherapy, it is imperative that chemotherapy is only administered to the appropriate patient population who are more likely to benefit. Cisplatin 100 mg/m² given in combination with radiation in the non-metastatic setting is the most widely tested regimen and remains the reference regimen. Cetuximab is also an alternative, but there is no data to support the use of cetuximab in a laryngeal preservation approach or in the postoperative setting.     

Pharmacotherapy for male breast cancer

Breast cancer in males is uncommon, occurring at ~ 1% of the rate of female breast cancer. Male breast carcinomas tend to be highly positive for hormone receptors, including oestrogen, progesterone and androgen receptors. Owing to this, hormone therapy is recommended as the primary treatment modality. Adjuvant therapy is recommended for male breast cancers with large size or positive axillary nodes. For metastatic disease, options for therapy include tamoxifen, orchiectomy, anti-androgens with or without luteinising hormone releasing hormone analogues or combination chemotherapy. The newer hormonal treatments, such as the selective aromatase inhibitors or novel antioestrogens, have not yet been well studied in male breast cancer but have potential for efficacy in this disease.     

Advances in cervical cancer pharmacotherapies

While widely employed in the management of cervical cancer, the overall utility of systemic anti-neoplastic agents in this clinical setting is quite modest. Cisplatin, the single most studied agent, is currently administered concurrently with external beam radiation as a component of “standard-of-care” in the management of locally advanced cervical cancer. Cisplatin (or carboplatin) combined with paclitaxel is the most commonly utilized regimen in the metastatic/recurrent disease setting (assuming the absence of evidence the cancer is resistant to platinum agents). Recently reported phase 3 trial data have demonstrated that the addition of bevacizumab to either a cisplatin/paclitaxel or paclitaxel/topotecan chemotherapy regimen improves overall survival in metastatic/recurrent cervical cancer.     

Integration of bevacizumab with chemotherapy doublets for advanced cervical cancer

Introduction: Historically, treatment options were limited for women diagnosed with late-stage or recurrent cervical cancer until recently. The publication of the results of GOG240 marks the beginning of the anti-angiogenesis era in cervical cancer. This randomized controlled trial showed significant improvements in response rates, progression-free survival and overall survival when bevacizumab was added to conventional chemotherapy in patients with metastatic, recurrent, or persistent cervical cancer. Bevacizumab is the first new drug to be approved in this disease in over 8 years. It is also the first biologic agent to be approved for use in patients with a gynecologic malignancy.

Areas covered: This review will highlight the evolution of combination chemotherapy for advanced cervical carcinoma, with particular emphasis on the recent ground-breaking research on the anti-angiogenesis therapy.

Expert opinion: Experts believe that the discoveries surrounding angiogenesis inhibitors have changed the standard of practice for women with incurable invasive cervical cancer. We will explore the advantages and disadvantages of anti-angiogenesis therapies. Ultimately, we hope that the research summarized here will one day alter the face of this disease by offering this high-risk population a rare commodity: survivorship.     

Plants and cervical cancer: an overview

Introduction: Cervical cancer, the second most common gynecological malignant tumor seriously harmful to the health of women, remains a leading cause of cancer-related death for women in developing countries. Although a large amount of scientific research has been reported on plants as a natural source of treatment agents for cervical cancer, it is currently scattered across various publications. A systematic summary and knowledge of future prospects are necessary to facilitate further plant studies for anti-cervical cancer agents.

Areas covered: This review generalizes and analyzes the current knowledge on the anti-cervical cancer properties and mechanisms involved for plants, and discusses the future prospects for the application of these plants.

Expert opinion: This review mainly focuses on the plants which have been scientifically tested in vitro and/or in vivo and proved as potential agents for the treatment of cervical cancer. The failure of conventional chemotherapy to reduce mortality as well as serious side effects involved makes natural products ideal candidates for exerting synergism and attenuation effects on anticancer drugs. Although the chemical components and mechanisms of action of natural plants with anti-cervical cancer potential have been investigated, many others remain unknown. More investigations and clinical trials are necessary to make use of these medical plants reasonably.     

An update on the current pharmacotherapy for endometrial cancer

Introduction: Endometrial cancer (EC) is the most common gynecologic malignancy in the developed world and is increasing in incidence. While the mainstay of treatment for EC is surgery followed by chemotherapy and/or radiation therapy, the available pharmacotherapies are rapidly and constantly evolving. Understanding these new therapies is an important part of the research and clinical care of women with EC. A review of available literature from MEDLINE (1879–2015) was conducted for the historic treatments and current therapies available for endometrial tumors.

Areas covered: This article reviews the current conventional therapies and discusses novel therapeutic agents, some of which are available to clinicians while others are currently being investigated in the preclinical setting.

Expert opinion: Genomic and immunohistochemical characterization of endometrial cancer may soon be the best approach for the identification of aggressive forms of tumor. Targeted therapies will soon be standard in the management of endometrial cancer.     

Pharmacotherapy of relapsed metastatic testicular cancer

Background: Patients with metastatic testicular cancer exhibit an excellent prognosis. However, the outcome for patients with relapse after cisplatin-based chemotherapy remains unsatisfactory. Several larger studies have been recently published. Objective: To review the treatment of patients with testicular cancer after failure of first-line chemotherapy. Methods: A literature search was performed for studies investigating therapies for relapsed testicular cancer. Results/conclusions: The prognosis of patients relapsing after first-line cisplatin-based chemotherapy has improved with multimodality therapy, including conventional and high-dose chemotherapy, surgery and radiation. Prognostic factors are increasingly used to guide treatment intensity. High-dose chemotherapy has become an accepted treatment option, in particular in patients with poor risk factors at relapse. The outcome of patients with multiply relapsed or cisplatin-refractory disease remains particularly poor. Treatment of relapsed patients requires a close cooperation of medical oncologists, urologists, surgeons and radiation oncologists with extensive experience in this disease.     

PI3K/AKT/mTOR信号通路抑制剂在宫颈癌治疗中的研究进展

宫颈癌是女性常见恶性肿瘤之一。针对局部晚期及复发转移的宫颈癌患者尚未有令人满意的治疗手段,因此探索和发展更有效的治疗方案具有重要的意义。PI3K/AKT/m TOR信号通路在人类子宫颈癌细胞的增殖、分化和凋亡中具有重要的调节作用,有希望成为开发宫颈癌治疗药物的新型靶标。综述了近年来PI3K/AKT/m TOR信号通路的单一及双重靶点抑制剂针对宫颈癌的临床前及临床研究情况,包括PI3K抑制剂(wortmannin、LY294002、吲哚-3-甲醇)、AKT抑制剂(SC-66、MK-2206、木黄酮、冬凌草甲素和雷公藤)、m TOR抑制剂(替西罗莫司和依维莫司)及双重靶点抑制剂(GSK2126458、BEZ235、BGT226、PF04691502、GDC-0980和PKI-587)等。     

Pharmacotherapy of asthma

The pharmacotherapy of asthma is a complex and evolving topic. A detailed understanding of the pathophysiologic processes involved in the asthmatic response forms the basis for understanding the actions of drugs used to treat this condition. Likewise, a solid comprehension of the medicinal chemistry and pharmacologic properties of the numerous agents involved in the treatment of asthma is critical for rationalizing drug choices and understanding potential side effects. Asthma is addressed at several points in the PharmD curriculum at South University including in the Pathophysiology (quarter 2), Integrated Sequence III (quarter 6), and Critical Care (quarter 9) courses. Various teaching strategies are employed throughout, along with weekly case-based recitations. The content presented here includes a synopsis of the pathophysiology and pharmacology from our Integrated Sequence III block on inflammatory diseases and asthma. A short review of pertinent pathophysiology is followed by a detailed presentation on the various classes of asthma drugs which includes their chemistry, mechanism of action, pharmacokinetics, toxicity, and interactions. This presentation is designed to prepare students for asthma therapeutics, which follows next in the schedule. The complexities of asthma pharmacotherapy are stressed along with current controversies and future drug development.     

Pharmacotherapy of anemia in cancer patients

Anemia is common in cancer patients who are receiving chemotherapy treatment and may result in symptoms such as fatigue and reduced exercise tolerance. Treatment with recombinant human erythropoietin, an erythropoiesis-stimulating agent (ESA), in anemic patients with solid tumors and nonmyeloid hematological malignancies results in an improvement in mean hemoglobin concentration, a reduction in transfusion requirement along with an improvement in quality of life scores. In patients with myelodysplasia, the response to single-agent ESAs is disappointing but combining ESAs with granulocyte colony-stimulating factor improves the response rates substantially. Unfortunately, a significant proportion of people remain refractory to treatment. Possible causes of ESA refractoriness include true or functional iron deficiency and concomitant intravenous iron supplementation improves response rates when compared with supplementation with oral iron. There are no factors that predict response to ESAs with sensitivity and specificity in people with nonmyeloid tumors, although a promising model for myelodysplasia has been developed that awaits large-scale evaluation. Treatment with ESAs is generally very safe, with just a small increased risk of venous thrombosis. Some recent data have suggested that ESAs may increase the risk of tumor progression in certain settings. These data are worrying but all the trials reporting this outcome have had flaws in design and further data are required.     

介入治疗用于巨块型宫颈癌手术前护理27例

目的：探讨巨块型宫颈癌术前介入治疗的有效护理措施，以提高护理质量。方法：对27例巨块型宫颈癌（Ⅰb～Ⅱa）均行子宫动脉灌注栓塞治疗1疗程，同时对患者进行心理、术前、术后的精心护理。结果：介入治疗顺利，无1例发生护理并发症。结论：通过介入治疗和精心护理能够提高患者疗效和生存质量，能为肿瘤根治性切除创造条件。     

新辅助化疗在非局部进展性早期宫颈癌应用的临床分析(附67例报告)

目的探讨如何进一步改善非局部进展性早期宫颈癌的预后。方法对2005年7月至2010年3月我院收治的67例非局部进展性早期宫颈癌患者的病历资料作回顾性分析。根据患者术后病理结果,分析影响预后的重要因素——脉管浸润和淋巴结转移,寻找与其关联的临床特征。结果肿瘤大小及间质浸润深度是非局部进展性早期宫颈癌脉管浸润及淋巴结转移的高危因素(P<0.05),年龄、病理类型及组织学分级均不是高危因素(P>0.05)。结论对肿瘤最大直径2～4cm或间质浸润深度超过1/2的非局部进展性早期宫颈癌患者可考虑行术前新辅助化疗,以改善预后。     

Pharmacotherapy of age-related macular degeneration

Background: Age-related macular degeneration is the leading cause of blindness in the developed world. The number of persons with vision loss from age-related macular degeneration is projected to increase dramatically over the next few decades. Therefore, effective therapeutic and prophylactic agents are greatly needed. Objective: This article will discuss some of the newer treatment strategies that may help to reduce the incidence of visual loss from age-related macular degeneration. Some of these therapies and strategies can be implemented today, while many are hypothetical based on current laboratory data and ongoing clinical trials. Methods: A review of the literature and ongoing clinical trials was undertaken. Conclusion: Current therapies using antioxidants for prevention of the progression of age-related macular degeneration and anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have given us tools for tackling this disease better and reducing the number of patients with vision loss. Combinations of some of the existing treatments and new forms of therapy may yet further decrease the treatment burden in the future.     

Investigational drugs for the treatment of cervical cancer

Introduction: Cervical cancer (CC) is currently the fourth most common malignant disease of women worldwide. Although the incidence and the mortality rates have been decreasing with screening detection and new treatment strategies, a significant number of metastatic or recurrent disease is still diagnosed. For those patients not amenable to curative treatments, such as surgery and radiation, palliative chemotherapy remains the standard of care. As chemotherapy regimens have limited activity, research is focalized on investigating novel pharmacologic strategies.

Areas covered: This paper aims to give a complete and updated overview on investigated therapies for the treatment of CC. The authors review the results of clinical studies and highlight the ongoing trials.

Expert opinion: Agents targeting various molecular pathways including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), poly ADP-ribose polymerase (PARP), epigenetics and other biological mechanisms represent interesting investigational opportunities. Amongst such drugs, bevacizumab, an anti-VEGF monoclonal antibody, was the first targeted drug recently approved by the FDA for the treatment of patients with metastatic, recurrent, or persistent CC. Another interesting experimental approach is represented by immunotherapy, which is leading to promising results with to the development of therapeutic vaccines and immune checkpoints inhibitors.     

顺铂或奈达铂联合紫杉醇治疗宫颈癌的疗效比较

目的 对比分析顺铂或奈达铂与紫醇联合治疗宫颈癌的疗效。方法 选择2012年2月-2015年12月在宁强县天津医院进行诊治的宫颈癌患者160例,按照使用化疗药物的不同分为顺铂组和奈达铂组。顺铂组采取TP化疗方案,奈达铂组采取TN化疗方案,对比两组的疗效、化疗不良反应、住院时间和治疗费用。结果 顺铂组的有效率为79.26%,与奈达铂组的82.05%相比无明显差异;奈达铂组Ⅰ~Ⅳ级血红蛋白降低、白细胞减少的发生率均明显高于顺铂组（P<0.05）,但两组间Ⅲ~Ⅳ级血红蛋白降低、血小板和白细胞减少发生率无明显差异,奈达铂组Ⅰ~Ⅳ级和Ⅲ~Ⅳ级恶心、呕吐发生率均明显低于顺铂组（P<0.05）;奈达铂组患者的住院时间明显短于顺铂组（P<0.05）;奈达铂组的治疗费用与顺铂组相比无明显差异。结论 顺铂或奈达铂与紫杉醇联合应用于宫颈癌辅助化疗的疗效相似,奈达铂的胃肠道不良反应比顺铂更低,骨髓抑制尽管增加但仍可控,采用奈达铂化疗较顺铂缩短了住院时间,且住院费用并无明显增加,患者更易接受。     

基于患者为中心的介入治疗与放射治疗联合疗法在中晚期宫颈癌治疗中的效果分析

目的 探讨基于患者为中心的介入治疗与放射治疗联合疗法在中晚期宫颈癌治疗中的临床效果,以期为优化宫颈癌治疗提供科学依据.方法 选取临床Ⅱb期以上的宫颈癌患者176例,根据治疗方法分为联合组(n=86)和对照组(n=90),对照组患者采用单纯根治性放疗,联合组患者则接受基于患者为中心的介入治疗与放射治疗联合疗法,比较两组患者近期临床疗效和近期、远期不良反应,统计并比较两组患者1、3年复发转移率和生存率.结果 联合组近期有效率为91.86%(79/86),对照组为77.78%(70/90),组间比较差异有统计学意义(P<0.05);两组患者近期不良反应均表现为消化道反应、骨髓抑制、肝肾损害,远期不良反应表现为放射性皮炎、放射性直肠炎、放射性膀胱炎,联合组患者放射性直肠炎、放射性膀胱炎的发生率均明显低于对照组患者(P<0.05);联合组患者1、3年内复发转移率分别为6.98%(6/86)、24.42%(21/86),对照组患者分别为16.67%(15/90)、38.89%(35/90),组间均差异有统计学意义(P<0.05);联合组患者1、3年内生存率分别为93.02%(80/86)、75.58%(65/86),对照组患者分别为85.55%(77/90)、60.00%(54/90),组间3年内生存率均差异有统计学意义(P<0.05),但1年内生存率差异无统计学意义(P>0.05).结论 基于患者为中心的介入治疗与放射治疗联合疗法是治疗中晚期宫颈癌的有效方法,可显著提高治疗效果,明显提高患者生存率,值得临床推广应用.     

中晚期宫颈癌同步放化疗的疗效分析

目的对比PF方案化疗配合放疗与单纯放疗治疗中晚期宫颈癌的近期疗效,探讨综合治疗的近期疗效和毒副反应。方法观察组(A组)32例予PF方案化疗同时行根治性放疗;对照组(B组)34例行单纯根治性放疗。结果同步放化疗组近期有效率90%,单纯放疗组76%,两组比较差异有显著性意义(P<0.05),毒副反应同步放化疗组发生率明显高于对照组,但均可耐受。结论同步放化疗可提高中晚期宫颈癌的近期疗效,毒副反应增加但可以耐受,不影响放疗进程。     

紫杉醇联合顺铂治疗早期巨块型宫颈癌疗效分析

目的探讨巨块型宫颈癌早期患者运用紫杉醇结合顺铂进行化疗的临床作用及影响。方法选取商丘市第一人民医院2009年5月至2012年10月收治的29例早期巨块型宫颈癌患者,术前对患者采取紫杉醇联合顺铂化疗方案,化疗后对根据患者病情实施子宫全切术或部分切除术,并行盆腔淋巴结清扫术,观察术后所有患者临床疗效。结果术后患者总有效率为82．76％。其中,病理完全缓解者3例;部分缓解者21例。结论巨块型宫颈癌由于肿块较大,手术困难,通过术前的化疗可以将肿块缩小,以方便手术并能够提高术后疗效。