Chemotherapy for prostate cancer

The clinical significance of chemotherapy for patients with hormone refractory prostate cancer(HRPC) is still controversial. Some randomized-controlled trials represented that mitoxantrone combined with prednisone (or hydrocortisone) provided palliative benefit to patients with HRPC. These treatments are well tolerated by elderly patients. On the other hand, the high PSA response rates have been observed in trials with both estramustine and taxane, however, higher toxicity was also recognized. The most relevant endpoint is not only palliative efficacy but also survival in these trials. Recently, the improvement of survival with docetaxel-based chemotherapy was reported. Further studies with chemotherapeutic agents will be needed to provide patients of HRPC good quality of life and longer survival.     

Treatment options for androgen-independent prostate cancer

Patients with recurrent prostate cancer may be treated with androgen deprivation strategies, but most patients will develop androgen-independent prostate cancer (AIPC). Current strategies for treatment of patients who develop AIPC have shown significant palliation, but no definitive increase in survival to date. The results of large chemotherapy trials with survival endpoints are expected soon. In addition, several novel drugs have proceeded through preclinical testing into early clinical trials. These drugs-either alone or in combination-are designed to target strategic pathways to improve survival and quality of life in patients. This article summarizes standard treatment options and promising new drugs and combination therapies under investigation for AIPC.     

Palliative chemotherapy in cancer patients

Palliative chemotherapy is applied for incurable cancer patients to prolong their survival, decrease their cancer-related symptoms, and improve their quality of life. These are important end points in clinical trials of palliative chemotherapy. A lot of clinical studies have demonstrated the palliative effect of chemotherapy for incurable cancers such as advanced pancreatic cancer, non-small cell lung cancer and so on. On the other hand, treatment with anti-cancer drugs can be harmful, and sometimes the toxicities may be very severe leading to worsened quality of life and shortened survival. So, we must carefully consider the application of palliative chemotherapy and discuss it with patients.     

老年进展期胃癌的外科治疗

胃癌是我国死亡率最高的恶性肿瘤之一,随着人口老龄化,老年患者逐渐增多。根治性手术是治愈进展期胃癌的唯一手段:D2胃癌根治术作为治疗进展期胃癌的标准术式已被普遍接受。几项临床试验已证实与D2根治术相比,扩大手术范围并未使患者术后生存率有更多的获益。为改善进展期胃癌患者的预后,必须强调开展术前TNM分期,以便临床医师根据肿瘤的状况选择合适的治疗方案。微创外科技术在进展期胃癌中的应用仍有争议,需要进一步研究。胃癌术后消化道重建方式是决定术后生活质量的关键因素,理想的重建方式仍有争议。     

Endpoints in cancer clinical trials: is there a need for measuring quality of life?

A review of the possible reasons to measure quality of life in cancer patients as well as reasons not to measure it is presented. These are considered in the context that standard endpoints already exist in cancer clinical trials and have served us well. Quality-of-life assessments might best be utilized in trials in which survival differences between treatments are expected to be small, which is frequently the case. Although more data are required to establish properly the true value of quality-of-life measurement in cancer clinical trials, such measurements should be encouraged.     

Prognostic impact of the combination of erythropoiesis-stimulating agents to cancer treatment: literature review

Cancer patients commonly develop anaemia. Erythropoiesis-stimulating agents (ESAs) are frequently used in cancer treatment. Numerous controlled studies indicate that ESAs can raise haemoglobin levels, reduce transfusion requirements and improve quality of life in anaemic cancer patients receiving chemotherapy. They were previously used to enhance response to radiation therapy, via increasing tumour cell oxygenation. Since the 2002 guideline, there has been increasing attention to the safety of ESA treatment in patients with cancer. Two placebo-controlled phase III randomised clinical trials published in 2003 showed evidence of harmful effects of ESAs on survival and/or tumour outcomes. Subsequently, recent trials and several large meta-analyses have confirmed negative impact on survival and/or disease progression. To comprehensively examine whether ESA use affects safety outcomes in cancer patients in different settings (chemotherapy, radiotherapy and targeted therapies), we conducted a literature review of all clinical trials, small and large meta-analyses from 1990 to 2012.     

Management of the elderly patient with advanced non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most lethal of the common solid malignancies. It is predominantly a disease of the elderly with the median age at diagnosis 68 years. Unfortunately, the majority of patients present with advanced disease whereby palliation is the primary aim of treatment. The elderly have a long history of undertreatment and non-inclusion in clinical trials with regard to cancer. Elderly-specific studies demonstrate that chemotherapy provides both a survival and quality-of-life benefit in advanced NSCLC. Increasing emphasis is placed on the objective assessment of fitness for chemotherapy and the integration of molecularly targeted agents into treatment paradigms.     

Survival benefit of eribulin mesylate in heavily pretreated metastatic breast cancer: What next?

Eribulin is a synthetic analog of halichondrin B, a non-taxane microtubule inhibitor extracted from the marine sponge, Halichondria okaida. It presents a novel mechanism of action and is active on cancer cells resistant to other antimicrotubule agents. It was granted approval in the USA and Europe for the treatment of heavily pretreated metastatic breast cancer. Early trials had shown activity in this setting with main toxicities being neutropenia and neuropathy in patients where quality of life is essential. Approvals were granted after a phase 3 trial demonstrated overall survival benefit in metastatic breast cancer previously treated with anthracyclines, taxanes, and capecitabine, in a setting where most treatments are failing to demonstrate a survival benefit. Recent data suggest that this survival benefit is also consistent in the elderly with no excess toxicity. Future strategies of eribulin are being tested in ongoing trials, evaluating this drug in earlier metastatic lines as well as in the adjuvant and the neoadjuvant settings.     

Measurement and management of health-related quality of life in lung cancer

The 5-year survival rate for lung cancer has been and remains very low, and patient experience is characterized by a heavy symptom burden leading to poorer health-related quality of life (HRQL). In light of these facts, treatment remains primarily palliative with a focus on improving quality of life, particularly through symptom management. Increasingly, clinical research has evaluated both traditional clinical endpoints as well as quality of life as primary outcome variables. This is due in part to recent data in which patient-reported health data have been found to have prognostic value in lung cancer. This paper reviews the literature to date about lung cancer survivors, HRQL conclusions from recent clinical trials, and several barriers to the incorporation of HRQL information into daily clinical practice. Finally, we describe some recent clinical applications of the integration of HRQL information into routine clinical practice with advanced lung cancer patients.     

Care of breast cancer in the elderly woman—what does comprehensive geriatric assessment (CGA) help?

Breast cancer is the most common cancer in women in Europe and Northern America. Its incidence and mortality rates are increasing with advance in age. Only few elderly women with breast cancer are treated in clinical trials. Elderly women with the same numerical age are very heterogeneous considering their biological age. Geriatric medicine has established comprehensive geriatric assessment (CGA) to get important information on elderly patients missed by a routine clinical history and physical examination. The data collected in CGA are of prognostic relevance for mortality, morbidity, maintenance of independence and utilisation of health care resources. Within the last few years, some research groups have demonstrated that the use of CGA in elderly cancer patients collects information missed by the currently established workup of these patients and that this information is of prognostic relevance concerning toxicity of chemotherapy and mortality. The use of CGA in a population of general elderly patients improves functional status and mental health, but so far no effect on mortality could be demonstrated. A subgroup analysis of the elderly cancer patients within this trial additionally demonstrated an improvement in pain control. Special data concerning the use of CGA within the group of elderly breast cancer patients are not published so far. The authors suggest areas of care for elderly women with breast cancer within which the CGA might be able to improve treatment and which should be a field of randomised controlled trials in the future.Presented as an invited lecture at the 15th International Symposium Supportive Care in Cancer, Berlin, Germany, June 18–21, 2003     

Non-small cell lung cancer therapy in the elderly

To date, lung cancer is still the leading cause of cancer-related mortality worldwide, with the majority of lung cancers arising in the elderly. As a consequence, we can expect an increase in the number of older lung cancer patients considered suitable for chemotherapy in the near future. Elderly patients often have comorbid conditions and progressive physiologic reduction of organ function, which can make the selection of proper treatment daunting. Some patients will be able to tolerate chemotherapy as well as their younger counterparts, whereas others will experience severe toxicity and require treatment modifications. Thus, a major issue is effectively selecting patients suitable for standard or attenuated therapy. A comprehensive geriatric assessment performed at baseline is a useful tool that can help select the best treatment regimen to be administered to elderly patients. Until now, few trials have specifically focused on elderly patients affected by non-small cell lung cancer (NSCLC), particularly those with advanced disease; prospective elderly-specific studies in early stages are still lacking. High priority should be given to evaluating the role of new targeted therapies. Unfortunately, to date, clinical trials that include functional status and comorbidity as part of the geriatric assessment are rare. Future trials, specifically in the elderly population, should include these kinds of evaluations. The most recent therapies for the treatment of elderly patients with NSCLC will be discussed here.     

A review of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation

BACKGROUND: Warfarin therapy has proved safe and effective in a number of randomized controlled trials of stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF), reducing the risk of stroke in these patients by two thirds. However, participants in the clinical trials were carefully selected and younger than patients in actual clinical practice. OBJECTIVE: This analysis sought to determine whether the results of clinical trials in patients with NV can be extrapolated to the general population seen in clinical practice. METHODS: A MEDLINE search from 1966 to the present was used to identify observational trials of anticoagulation in patients with NVAF that addressed warfarin use, anticoagulation control, efficacy, and complications. The search terms used were atrial fibrillation and anticoagulation. RESULTS: Although warfarin prophylaxis against stroke in patients with NVAF appeared to be as well tolerated and effective in clinical practice as in clinical trials, it was generally underused, particularly in the elderly. Anticoagulation control was not as good in clinical practice as in clinical trials, although the rates of stroke and major bleeding were comparable. CONCLUSIONS: Judicious use of warfarin, tailored to individual stroke risk, seems to be a reasonable policy. Warfarin therapy increases quality-adjusted survival in patients at high risk for stroke, and it is recommended for medium-risk patients unless their risk of bleeding is high or their quality of life while taking warfarin would be poor. Patients at a low risk for stroke will have equivalent health outcomes and incur lower costs if treated with aspirin. Despite the increased risk of hemorrhage in elderly patients, the net benefit of warfarin therapy is greater in this age group because of the higher risk of stroke. Active involvement of patients and their caregivers in an anticoagulation service setting may improve outcomes of anticoagulation therapy.     

高龄低位直肠癌的外科治疗68例报告

目的分析高龄低位直肠癌临床特点、外科治疗方式及围手术期处理。方法回顾性分析75岁以上行手术治疗的68例低位直肠癌患者的临床资料。结果全组病例入院前误诊率高(47.1%),并存病多(67.6%),肿瘤切除率高(94.1%),术后并发症发生率高(42.7%)。结论早期诊断治疗,积极处理并存病,恰当的手术方式,充分的围手术期处理,对于减少手术风险、获得长期存活率、提高术后生活质量极为重要。     

Immunotherapy for prostate cancer - recent progress in clinical trials

Prostate cancer is the most common malignancy affecting men in the United States. Traditional therapy with radical prostatectomy or radiation therapy can be curative for localized disease, but metastatic prostate cancer is currently incurable. The only treatments known to prolong survival in patients with metastatic disease are androgen-deprivation therapy and chemotherapy, both of which have significant side effects. Immunotherapy approaches offer hope in providing new treatments to delay disease progression, ideally with fewer side effects. The results from nearly all early immunotherapy clinical trials for prostate cancer conducted to date have shown minimal toxicity, and many have suggested clinical benefit in terms of delaying disease progression. Several phase III clinical trials are currently under way in patients with metastatic, androgen-independent prostate cancer. The current article reviews recent trials evaluating immune-modulating agents, antigen-specific active immunotherapy, and combination therapies in clinical development for the treatment of prostate cancer.     

Cost-Effectiveness of Second-Line Chemotherapy/Biologics among Elderly Metastatic Colon Cancer Patients

Introduction

Advancements in chemotherapy treatment have improved the clinical management of metastatic colon cancer (mCC) patients. An increasing number of elderly mCC patients receive various combinations of regimens in second-line chemotherapy/biologics treatment (Tx2) after first-line treatment (Tx1) to prolong survival and/or palliate symptoms, but these regimens have higher costs. This analysis investigated the survival benefit and incremental cost associated with Tx2 among elderly mCC patients.

Methods

Elderly (aged ≥66 years) SEER-Medicare patients diagnosed with mCC in 2003–2007 were identified and followed until death or the end of 2009. Cox regression and partitioned least squares regression were utilized to obtain the survival benefit and incremental cost associated with Tx2 within a 5-year study period. A time-varying model was used to reduce bias due to sequential ordering of Tx1 and Tx2. The regressions controlled for patient demographic characteristics, clinical variables, and a proxy for poor performance. Bootstrapping was used to generate 95% confidence intervals (CI).

Results

Of the 3,266 elderly mCC patients who received Tx1, 2,744 (84%) died within the observation period; 1,440 (44%) received Tx2. The survival benefit associated with receipt of Tx2 was 0.33 years (95% CI 0.19–0.43), and the associated incremental cost was $40,888 (95% CI 3,044–44,324). The incremental cost-effectiveness ratio (ICER) for Tx2 was $123,903 per life year gained (95% CI 9,600–216,082).

Conclusion

The estimated survival benefit of receiving second-line chemotherapy/biologics was about 4 months, which is consistent with evidence from clinical trials. This improved survival was associated with an ICER that exceeds the traditional threshold.     

Adopting extensive intra-operative peritoneal lavage (EIPL) as the standard prophylactic strategy for peritoneal recurrence

EIPL (extensive intra-operative peritoneal lavage) therapy was developed as a prophylactic strategy for peritoneal recurrence, with the goal of improving the quality of life and survival span for advanced gastric cancer patients with peritoneal free cancer cells. The purpose of this article is to review the therapy's contribution to a remarkable improvement in the 5-year survival for patients with positive lavage cytology on prospective randomized controlled clinical trials. We also advocate for the adoption of the EIPL as the optimal treatment protocol for advanced gastric cancer.     

Gastrointestinal cancer refractory to chemotherapy: a role for octreotide?

Although octreotide has been shown to inhibit the growth of gastrointestinal (GI) tumors in vitro and in vivo, preliminary clinical trials have reported disappointing results for this somatostatin analog in patients with GI cancers. The results of these trials probably reflect the difficulty in assessing the therapeutic potential of an agent such as octreotide in GI cancers. Thus, it is possible that treatment with octreotide could be useful in the stabilization of disease if it is associated with an improvement in survival. On the basis of these considerations five randomized trials were carried out to evaluate the therapeutic potential in patients with GI cancers. Four trials (one in patients with colorectal carcinoma and three in patients with carcinoma of the pancreas) did not show any advantage of octreotide in untreated patients; in contrast, one trial reported that octreotide prolonged survival in patients with GI cancers refractory to chemotherapy. Some clinical features of the latter study (treatment with chemotherapy, different schedules) may explain these conflicting results. Although data from randomized trials suggest that octreotide is not effective in untreated asymptomatic advanced GI cancer patients, further studies are warranted to assess the efficacy of octreotide in chemotherapy refractory patients in order to clarify the impact of octreotide in terms of not only survival but also on the patients' quality of life.     

沙利度胺联合放疗治疗老年晚期胃癌患者临床疗效及安全性分析

目的探讨沙利度胺联合放疗方案治疗晚期胃癌的临床疗效及安全性,为晚期胃癌治疗提供一定参考。方法选取我院收治的89例老年晚期胃癌患者,根据非随机临床同期对照研究及自愿原则将患者分为观察组(n=47)和对照组(n=42),对照组采用调强放疗技术进行治疗,观察组在对照组基础上同时服用沙利度胺治疗。对比两组临床疗效及不良反应,检测血管生成相关指标,评价患者生活质量。结果观察组疾病治疗有效率和疾病控制率均高于对照组,血清血管内皮生长因子(VEGF)、神经纤毛蛋白-1(NRP-1)水平均低于对照组(P<0.05);观察组总生存期及无进展生存期均长于对照组(P<0.05)。结论沙利度胺联合放疗治疗老年晚期胃癌患者肿瘤生长得到明显抑制,临床疗效较好,患者生活质量更高,生存期更长,不良反应较少,安全性较高,值得在临床治疗中推广。     

Adjuvant chemotherapy for non-small-cell lung cancer

Survival rates following complete resection for patients with non-small-cell lung cancer are disappointing. Only 60-70% of patients with stage I disease (no lymph node involvement) are expected to survive 5 years. Attempts to improve survival have included the use of chemotherapy, radiation, or both before or after surgery. The majority of randomized trials examining the use of postoperative therapies have not found a survival benefit. Many of these trials have enrolled small numbers of patients and have been underpowered to detect small, but significant, survival differences. Recent data from large, randomized international trials have yielded conflicting results. The use of postoperative therapy should continue to be studied in clinical trials and a new meta-analysis incorporating results from recently completed randomized trials should be conducted.     

Clinical trial recruitment challenges with older adults with cancer

Older adults continue to be disproportionately represented in research studies and cancer-related clinical trials. As survival rates for patients with cancer continue to increase, it is critical that we begin to gather data on how to provide the best care to the patient population where cancer is most prevalent. The purpose of this article was to provide an overview of barriers encountered during recruitment to clinical trials of older patients with cancer. Two clinical trials involving older patients with cancer are presented to describe strategies used by the principal investigators to enhance recruitment and enrollment to their clinical research trials. These two exemplars suggest that planning and regular meetings by the research team and transparent communication are essential for successful clinical trial recruitment of older patients with cancer.