The role of cytokines in oncology

The availability of sufficient quantities of recombinant human cytokines and promising preclinical data have led to their introduction into clinical trials. Cytokines have potential as new therapeutic agents in a variety of hematological disorders as well as in solid tumors. Only a few of the still increasing number of these glycoprotein hormones have been studied in humans so far, either as single agents or in combination with chemotherapy and other cytokines. Their clinical effects, beneficial role in supportive care, and use in the treatment of certain cancer patients are reviewed.     

Current standard and investigational approaches to the management of hormone-refractory prostate cancer

Prostate cancer is a common cause of death in men and remains incurable in the metastatic setting. In 2004, 2 landmark trials using docetaxel-based chemotherapy, TAX 327 and SWOG 99-16, showed a survival benefit for the first time in metastatic, hormone-refractory prostate cancer. Current research suggests that several distinct mechanisms of androgen-refractory disease may converge in patients with disease progression on androgen deprivation therapy. These findings have identified several potential targets for therapeutic intervention. Current standard and investigational treatment options for this disease are discussed, including chemotherapy and rapidly evolving therapies in phase II/III trials involving antiangiogenic therapies, signal transduction inhibitors, immunomodulatory agents, and nuclear receptor targets. In light of a growing array of treatment options and an increasingly chronic natural history, this review supports a multidisciplinary care approach to these patients, including medical oncologists, urologists, and radiation oncologists, to optimize survival and quality of life.     

Virtual reality and music therapy as distraction interventions to alleviate anxiety and improve mood states in breast cancer patients during chemotherapy

Psychological distress is a common consequence of breast cancer diagnosis and treatment and could further exacerbate therapy side effects. Interventions increasing treatment tolerance are crucial to improve both patients' quality of life and adherence to therapies. Virtual reality (VR) has emerged as an effective distraction tool for different medical procedures. Here, we assessed the efficacy of immersive and interactive VR in alleviating chemotherapy-related psychological distress in a cohort of Italian breast cancer patients, also comparing its effects with those of music therapy (MT). Thirty patients were included in the VR group, 30 in the MT group, and 34 in the control group, consisting of patients receiving standard care during chemotherapy. Our data suggest that both VR and MT are useful interventions for alleviating anxiety and for improving mood states in breast cancer patients during chemotherapy. Moreover, VR seems more effective than MT in relieving anxiety, depression, and fatigue.     

A short history of SFRR-Asia,its current status and significance

Antineoplastic agents are known to induce the production of free radicals leading to cell damage. These adverse effects may fuel the acquisition of new mutations and the development of treatment resistances. We selected 30 metastatic breast cancer patients receiving palliative chemotherapy, and paired blood samples, before and after chemotherapy, were extracted. We analysed DNA, lipid and protein oxidative damage markers and determined the extent of antioxidant and repair defences activation at the systemic level. We found that the DNA repair activity of the KU86 enzyme was significantly lower after chemotherapy and the antioxidant capacity of the plasma was significantly higher after treatment. Cox regression analysis revealed a significant effect of KU86 activity on the survival rates of those patients who received anthracyclines as part of their treatment. The high clinical heterogeneity of metastatic breast cancer patients warrants further studies to clarify the role of DNA repair and systemic antioxidant capacities during chemotherapy.     

Oxidative stress status in metastatic breast cancer patients receiving palliative chemotherapy and its impact on survival rates

Antineoplastic agents are known to induce the production of free radicals leading to cell damage. These adverse effects may fuel the acquisition of new mutations and the development of treatment resistances. We selected 30 metastatic breast cancer patients receiving palliative chemotherapy, and paired blood samples, before and after chemotherapy, were extracted. We analysed DNA, lipid and protein oxidative damage markers and determined the extent of antioxidant and repair defences activation at the systemic level. We found that the DNA repair activity of the KU86 enzyme was significantly lower after chemotherapy and the antioxidant capacity of the plasma was significantly higher after treatment. Cox regression analysis revealed a significant effect of KU86 activity on the survival rates of those patients who received anthracyclines as part of their treatment. The high clinical heterogeneity of metastatic breast cancer patients warrants further studies to clarify the role of DNA repair and systemic antioxidant capacities during chemotherapy.     

Cancer Pharmacogenomics May Require Both Qualitative and Quantitative Approaches

Resistance to chemotherapy is a major cause of mortality in patients receiving treatment for most types of cancer, and overcoming drug resistance has become an important focus of current research. A major clinical challenge is the fact that most anticancer drugs have a narrow therapeutic range, that is, their effective dose is relatively close to that associated with substantial toxicity. Significant advances have been achieved in event-free survival of patients with many types of cancer (most dramatically childhood acute lymphoblastic leukemia, ALL) through a better understanding of the pathobiology of human cancers, the cellular mechanisms of cancer chemotherapy, and the determinants of inter-individual differences in drug effects and treatment response. It is anticipated that expanding our knowledge of these areas will lead to the development of new anticancer agents and to more effective use of existing cancer chemotherapy. Pharmacogenomics research aims to elucidate the genetics determinants of drug efficacy and toxicity. Results of recent studies indicate that both qualitative and quantitative genomic analyses may be required for precise pharmacogenomic characterization of some types of human cancer.     

Cost Trend Analysis of Initial Cancer Treatment in Taiwan

Background

Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment.

Methodology/Principal Findings

The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI) system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05). Hospitalization costs comprised the largest portion of payments for all cancers. During 1996–2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05). In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share.

Conclusions/Significance

In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit from these expensive treatments.     

Chemotherapy and molecular therapy in cervical cancer

In recent years, the treatment of locally-advanced and metastatic cervical cancer has improved greatly due to the introduction of targeted therapies, new chemotherapy combinations, and emerging treatments. Candidates for potentially curative treatment are those patients with good functional status without associated comorbidities. Numerous trials have demonstrated that chemotherapy prolongs survival versus supportive care alone. In addition, polychemotherapy schemes are superior to single agent regimens. Targeted molecular agents have proven beneficial in the treatment of cervical cancer. Second-line treatment should be considered standard practice in patients with good functional status. Finally, given the poor survival outcomes in patients with metastatic disease, participation in clinical studies should always be considered the best option.     

Clinical breast cancer, new developments in selection and endocrine treatment of patients.

Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties.     

The Facilitating Role of Chemotherapy in the Palliative Phase of Cancer: Qualitative Interviews with Advanced Cancer Patients

Objective

To explore the extent to which patients have a directing role in decisions about chemotherapy in the palliative phase of cancer and (want to) anticipate on the last stage of life.

Design

Qualitative interview study.

Methods

In depth-interviews with 15 patients with advanced colorectal or breast cancer at the medical oncology department in a Dutch teaching hospital; interviews were analysed following the principles of thematic content-analysis.

Results

All patients reported to know that the chemotherapy they received was with palliative intent. Most of them did not express the wish for information about (other) treatment options and put great trust in their physicians’ treatment advice. The more patients were aware of the severity of their disease, the more they seemed to ‘live their life’ in the present and enjoy things besides having cancer. Such living in the present seemed to be facilitated by the use of chemotherapy. Patients often considered the ‘chemotherapy-free period’ more stressful than periods when receiving chemotherapy despite their generally improved physical condition. Chemotherapy (regardless of side-effects) seemed to shift patients’ attention away from the approaching last stage of life. Interestingly, although patients often discussed advance care planning, they were reluctant to bring on end-of-life issues that bothered them at that specific moment. Expressing real interest in people ‘as a person’ was considered an important element of appropriate care.

Conclusions

Fearing their approaching death, patients deliberately focus on living in the present. Active (chemotherapy) treatment facilitates this focus, regardless of the perceived side-effects. However, if anxiety for what lies ahead is the underlying reason for treatment, efforts should be made in assisting patients to find other ways to cope with this fear. Simultaneously, such an approach may reduce the use of burdensome and sometimes costly treatment in the last stage of life.     

动脉介入新辅助化疗对宫颈癌细胞增殖及凋亡的影响

目的:探讨动脉介入新辅助化疗对宫颈癌细胞增殖及凋亡的影响,为中晚期宫颈癌的临床治疗提供依据。方法:选择2012年8月-2015年5月在我院确诊为中晚期宫颈癌并行动脉介入化疗的患者60例作为研究对象。分别在入院时和动脉介入化疗后收集患者肿瘤组织标本,应用免疫组化法检测肿瘤细胞增殖指数(LI),TUNEL法检测肿瘤细胞凋亡指数(AI)。结果:经动脉介入化疗后,宫颈癌细胞的增殖指数显著降低,而凋亡指数显著提高,与化疗前比较,差异具有统计学意义(P0.05)。宫颈癌细胞增殖指数LI随临床分期的增加而升高,而凋亡指数AI随临床分期的增加而降低,差异具有统计学意义(P0.05);介入化疗后,同一临床分期宫颈癌细胞的增殖指数LI均低于化疗前,而凋亡指数AI则高于化疗前,差异具有统计学意义(P0.05)。结论:动脉介入新辅助化疗能够抑制中晚期宫颈癌细胞的增殖,并促进其凋亡,为患者创造手术切除的机会。     

Current indications for prevention and therapy of steroid-induced osteoporosis in men and women

Steroid-induced osteoporosis is a textbook example of the secondary type of this medical condition. Glucocorticosteroids suppress bone formation by their direct and indirect effect on osteoblasts, osteoclasts and osteocytes, increasing their resorption and, eventually, leading to negative bone balance. A clinical problem arises regarding the fact that approximately 50% of patients on chronic steroid therapy undergo asymptomatic bone fractures. The treatment mode includes minimising the dose of administered steroids, encouraging an improved lifestyle and supplementation with adequate calcium and vitamin D(3) doses. Bisphosphonates are a group of medical agents used both to prevent and treat steroid-induced osteoporosis, although new therapies have also become available in recent years.     

Current indications for prevention and therapy of steroid-iduced osteoporosis in men and women

Steroid-induced osteoporosis is a textbook example of the secondary type of this medical condition. Glucocorticosteroids suppress bone formation by their direct and indirect effect on osteoblasts, osteoclasts and osteocytes, increasing their resorption and, eventually, leading to negative bone balance. A clinical problem arises regarding the fact that approximately 50% of patients on chronic steroid therapy undergo asymptomatic bone fractures. The treatment mode includes minimising the dose of administered steroids, encouraging an improved lifestyle and supplementation with adequate calcium and vitamin D3 doses. Bisphosphonates are a group of medical agents used both to prevent and treat steroid-induced osteoporosis, although new therapies have also become available in recent years.     

Biology of brain metastases and novel targeted therapies: Time to translate the research

Brain metastases (BM) occur in 20% to 40% of patients with cancer and result in significant morbidity and poor survival. The main therapeutic options include surgery, whole brain radiotherapy, stereotactic radiosurgery and chemotherapy. Although significant progress has been made in diagnostic and therapeutic methods, the prognosis in these patients remains poor. Furthermore, the poor penetrability of chemotherapy agents through the blood brain barrier (BBB) continues to pose a challenge in the management of this disease. Preclinical evidence suggests that new targeted treatments can improve local tumor control but our clinical experience with these agents remains limited. In addition, several clinical studies with these novel agents have produced disappointing results. This review will examine the knowledge of targeted therapies in BM. The preclinical and clinical evidence of their use in BM induced by breast cancer, non-small cell lung cancer and melanoma will be presented. In addition, we will discuss the role of antiangiogenic and radiosensitising agents in the treatment of BM and the current strategies available to increase BBB permeability. A better understanding of the mechanism of action of these agents will help us to identify the best targets for testing in future clinical studies.     

Detection of oxaliplatin-induced DNA crosslinks in vitro and in cancer patients using the alkaline comet assay

Oxaliplatin is frequently used in the therapy of cancer. In DNA, oxaliplatin induces, like cisplatin, the formation of crosslinks, which are commonly accepted as being responsible for the cytotoxicity of platinum agents. The detection of oxaliplatin-induced DNA crosslink formation and repair could be a good measure of assessing how a patient is responding to the agent. In this study, we used a validated modification of the alkaline comet assay for detecting the presence of these crosslinks in vitro and in cancer patients. The H460 tumour cell line was treated in vitro with a range of oxaliplatin and cisplatin doses, and the subsequent crosslink formation and repair compared between the two agents. In addition, lymphocytes from cancer patients undergoing oxaliplatin-based chemotherapy were assayed for the formation and repair of oxaliplatin-induced crosslinks. A dose-response was observed in the in vitro samples, with cisplatin producing more crosslinks than oxaliplatin at equimolar concentrations and lesions induced by both agents showing different repair efficiencies. Furthermore, evidence of crosslink formation and repair was observed in the peripheral blood lymphocytes of all cancer patients studied, along with the detection of interindividual variability in crosslink formation and repair efficiencies. To the best of our knowledge, this is the first time that oxaliplatin DNA crosslinks have been detected either in vitro or in patient samples using the alkaline comet assay. Due to its sensitivity, rapidity, small cell sample and low cost, the alkaline comet assay is a good method for the detection of oxaliplatin-induced crosslinks and their subsequent repair and, in future clinical studies, could prove to be a valuable tool in assessing/predicting a patient's response to chemotherapy.     

The management of cancer in the elderly: targeted therapies in oncology

Cancer is universally considered a disease of ageing. Today the management of elderly cancer patients poses many specific problems and it should be revisited in the light of the most recent advances in both diagnosis and treatment of human malignancies. In particular, the potential use of novel therapeutic options, based on therapeutic agents raised against molecular targets (the so called targeted therapy), appears to be promising in this clinical settings especially in view of the limited side-effects. The mainstays of cancer treatment during the twentieth century were surgery, radiation and chemotherapy. However, surgery is not curative in metastatic disease, radiation and chemotherapy are limited by side effects because they can't discriminate between healthy and cancerous cells. When key molecular changes responsible for malignant transformation were identified (e.g. growth factors and their receptors), it was hoped that new targeted agents, by inhibiting cancer-specific pathways, would spare normal cells and thereby offer improved safety benefits and a higher therapeutic index over standard chemotherapeutics. The most common targeted therapies used in clinical practice, i.e. monoclonal antibodies and small molecules, are described.     

The role of adjuvant chemotherapy in the treatment of non-small cell lung cancer

Postoperative treatments for lung cancer have been evaluated for more than two decades, but in the majority of the studies (especially until 1990) no significant effect on survival has been shown. In 1995, a meta-analysis of eight cisplatin-based adjuvant chemotherapy trials with NSCLC showed a 13% reduction in the risk of death (P=0.08) and 5% benefit in 5-year survival. Among four positive trials (IALT, JBR10, ANITA and CALGB study) the absolute increase in the 5-year survival rates by adjuvant chemotherapy ranged from 4% to 15%, and the hazard ratios for death ranged from 0.6 to 0.86. The author analyzes the most important studies. Conclusion: adjuvant chemotherapy after complete resection of NSCLC can be considered as a new standard of care in patients with good performance status. Patients should receive 4 cycles of platina-based chemotherapy beginning 4-8 weeks after surgery. Future perspectives: optimization of chemotherapy regimens including targeted therapy (such as EGFR inhibitors, angiogenesis inhibitors, anti-EGFR monoclonal antibodies). Further progress is anticipated through the integration of chemopreventive agents into the adjuvant treatment.     

Circadian rhythms measured by actigraphy during oncological treatments: a systematic review

During oncological treatment patients often suffer from fatigue, insomnia, and daytime inactivity. This cluster of symptoms and overall survival are linked with circadian rhythm disruptions in rest-activity, which can be objectively characterized using actigraphy. We systematically reviewed the body of literature using actigraphy to characterize the circadian rhythm disruption in patients during oncological treatments and studies that introduced interventions to deal with this disruption. Thirteen observational and two interventional studies were included in this review. These mainly described patients with breast cancer undergoing chemotherapy, and the disruptions were persistent among these patients, and the disruptions peaked at the start of chemotherapy cycles and decreased during the periods in between. Light and behavioral therapy showed some alleviating effects in patients with breast cancer. We also found that circadian rhythm disruptions were prevalent in patients during other cancer therapies. Effective cancer therapy controls cancer growth and improves circadian organization. Cancer therapy itself, however, also contributes to cancer associated circadian dys-synchrony. Interrupting this vicious cycle represents an important opportunity for diminishing cancer patients’ suffering and improving or even prolonging their useful and enjoyable lives.     

Role of stem cells in cancer therapy and cancer stem cells: a review

For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research field and possible potential future treatment modalities for the cancer. Aim of this review is primarily focus on the recent developments in the use of the stem cells in the cancer treatments, then to discuss the cancer stem cells, now considered as backbone in the development of the cancer; and their role in carcinogenesis and their implications in the development of possible new cancer treatment options in future.