Cancer Treatment Reviews

Editorial Board

2010-02-01

Giant cell tumor of the extremity: A review of 349 cases from a single institution

2009-11-02

Summary: Giant cell tumor is still one of the most controversial and discussed bone tumors. Surgical treatment options include intralesional excision or segmental resection. Curettage has a higher recurrence rate but does preserve adjacent joint function. After curettage, the use of adjuvant therapies is still controversial. Three hundred forty-nine patients with giant cell tumors of the extremity, treated in a single institution, were analyzed in a retrospective study. Two hundred patients underwent curettage of the lesion and in 64 of these cases, three local adjuvants, such as phenol, alcohol and cement, were employed. The hypothesis is that an “aggressive curettage” with phenol, alcohol and cement provides better local control and functional results. The correlation between tumor in the proximal femur and higher recurrence rate has not been recorded before. The results of the present study suggest that an “aggressive curettage” reduces the recurrence rate in a disease whose aggressiveness is not easy to predict. Special attention must be given to giant cell tumors not only in the distal radius, but also in the proximal femur, where the treatment is more difficult and associated with a higher rate of local recurrence.

Target genes suitable for silencing approaches and protein product interference in ovarian epithelial cancer

Anastasia Malek, Reinhold Schäfer, Oleg Tchernitsa — 2009-11-30

Summary: Gene expression profiling studies and conventional approaches for the identification of genes involved in the initiation and progression of ovarian cancer have identified a plethora of potential therapeutic targets. This review summarizes the targets that show promise for specific interference in cancer cells, groups them according to their subcellular localization and involved biological processes and discusses their impact on experimental, pre-clinical and clinical therapy.

Treating the individual: The need for a patient-focused approach to the management of renal cell carcinoma

Camillo Porta, Joaquim Bellmunt, Tim Eisen, Cezary Szczylik, Peter Mulders — 2009-10-12

Summary: Five targeted agents have shown efficacy in advanced renal cell carcinoma. These agents were evaluated in pivotal phase III clinical trials using different treatment settings and different patient populations. As patients encountered in ‘real life’ clinical practice are frequently under-represented in phase III trials, making treatment decisions based on phase III data alone may have limitations. In order to support treatment decisions for patients who do not fit within the inclusion criteria of many phase III trials, physicians must consider additional data sources such as expanded access programmes, sub- and retrospective analyses, and also clinical experience. The suitability of a specific targeted agent for a given patient group, e.g. elderly, will depend on a number of factors, including disease-, patient- and treatment-related characteristics.Here, we identify the need for an individualised patient-focused approach to the management of advanced renal cell carcinoma in clinical practice. In order to optimise therapy for individual patients, we present a schema providing guidance on the wide range of parameters that should be considered when making treatment decisions. We recommend the integration of this approach into everyday clinical practice.

Second-line treatment for malignant pleural mesothelioma

2009-10-30

Summary: Most patients affected by malignant pleural mesothelioma (MPM) are candidates for chemotherapy during the course of the disease, as single modality treatment or within the context of a multimodality approach. Following the results of a large phase III trial, the combination of cisplatin and pemetrexed has become the preferred first-line chemotherapy, although there is also evidence for the activity of the combination with carboplatin based on phase II studies. Unfortunately, nearly all MPM patients progress during or after first-line treatment. Second-line therapies are being increasingly used in the clinical practice because patients are frequently still healthy at the time of disease progression. However, the role of these treatments in MPM is unproven, and the optimal regimens still remain to be defined.In pemetrexed-naïve patients, data from a randomized trial vs. best supportive care suggest the use of single-agent pemetrexed as a standard second-line treatment. This evidence is supported also by the results of the Expanded Access Programs. To date, there is still no standard approach for the growing population of pemetrexed-pre-treated patients. In selected cases with a prolonged response to first-line pemetrexed-based chemotherapy, re-treatment with a pemetrexed-based regimen should be considered. When a trial is not available or patients are not eligible for an experimental approach, single-agent vinorelbine can be a reasonable option for palliation. However, second-line therapy in MPM remains an ideal field in which to test new chemotherapy agents as well as new therapeutic strategies, including anti-angiogenic compounds, small molecules or monoclonal antibodies that target different molecular pathways.

Novel therapeutic approaches to the treatment of metastatic breast cancer

2009-11-02

Abstract: Metastatic breast cancer is ultimately an incurable disease, although recent data have shown that its incidence is decreasing and that patients with metastatic breast cancer live longer. This improvement in survival seems to be linked with the introduction of new therapeutic agents, novel combinations of existing therapies and targeted therapies. Our increasing understanding of the molecular biology of metastatic disease has allowed the development of therapies aimed at specific molecular targets. Some of these have already been approved for the treatment of metastatic breast cancer in combination with cytotoxics, and others have shown promising results regarding disease-free survival, overall response rates and time to disease progression. Given the enormous amount of information about drug discovery in cancer, it is important to be familiar with the present state of the treatment of metastatic breast cancer. The purpose of this review is to provide an update on the development of some of the most promising novel agents and treatment strategies in metastatic breast cancer.

Resveratrol in the chemoprevention and treatment of hepatocellular carcinoma

Anupam Bishayee, Themos Politis, Altaf S. Darvesh — 2009-11-12

Summary: Hepatocellular carcinoma (HCC) is one of the most common cancers and lethal diseases in the world. Although the majority of HCC cases occur in developing countries of Asia and Africa, the prevalence of liver cancer has risen considerably in Japan, Western Europe as well as the United States. HCC most commonly develops in patients with chronic liver disease, the etiology of which includes viral hepatitis (B and C), alcohol, obesity, iron overload and dietary carcinogens, including aflatoxins and nitrosamines. The current treatment modalities, including surgical resection and liver transplantation, have been found to be mostly ineffective. Hence, there is an obvious critical need to develop alternative strategies for the chemoprevention and treatment of HCC. Oxidative stress as well as inflammation has been implicated in the development and progression of hepatic neoplasia. Using naturally occurring phytochemicals and dietary compounds endowed with potent antioxidant and antiinflammatory properties is a novel approach to prevent and control HCC. One such compound, resveratrol, present in grapes, berries, peanuts as well as red wine, has emerged as a promising molecule that inhibits carcinogenesis with a pleiotropic mode of action. This review examines the current knowledge on mechanism-based in vitro and in vivo studies on the chemopreventive and chemotherapeutic potential of resveratrol in liver cancer. Pre-clinical and clinical toxicity studies as well as pharmacokinetic data of resveratrol have also been highlighted in this review. Future directions and challenges involved in the use of resveratrol for the prevention and treatment of HCC are also discussed.

Switching from tamoxifen to aromatase inhibitors for adjuvant endocrine therapy in postmenopausal patients with early breast cancer

C.J.H. van de Velde, S. Verma, J.G.H. van Nes, C. Masterman, K.I. Pritchard — 2009-11-30

Summary: The third-generation aromatase inhibitors (AIs), including anastrozole, exemestane and letrozole, have demonstrated improved efficacy versus tamoxifen for the adjuvant endocrine treatment of postmenopausal patients with hormone receptor-positive breast cancer. AIs can be used in several adjuvant endocrine settings: as upfront therapy, switch to an AI after 2–3years of tamoxifen or extended therapy following 5years of tamoxifen. In the switch setting, two different types of study designs have been utilized. One is a late randomization design which randomizes patients who are disease-free after 2–3years of tamoxifen to receive an AI versus continuation of tamoxifen. In contrast, an early randomization design randomizes all patients immediately after primary treatment and prior to starting tamoxifen. Efficacy benefits with AIs have been shown in several trials evaluating the late randomization strategy, including the Intergroup Exemestane Study, the Italian Tamoxifen Anastrozole trial and the Anastrozole-Nolvadex 95 trial. Similarly, early randomization studies, including the Austrian Breast and Colorectal Cancer Study Group-8 and the Breast International Group (BIG) 1–98 trial, have demonstrated the effectiveness of receiving an AI after tamoxifen. Two trials are assessing an early switch strategy versus upfront AI therapy: the BIG 1–98 trial and the ongoing Tamoxifen Exemestane Adjuvant Multicentre trial are assessing switching from tamoxifen to an AI after 2–3years versus upfront AI therapy. This paper reviews studies that have investigated a switch strategy with AIs and considers the implications of these data on treatment choice for postmenopausal patients with hormone receptor-positive breast cancer.

Combined treatment strategies in gastrointestinal stromal tumors (GISTs) after imatinib and sunitinib therapy

2009-11-16

Abstract: Resistance to tyrosine-kinase inhibitors remains an open issue in the treatment of patients with gastrointestinal stromal tumors. The complex biology of disease in the multi-resistant setting has led a progressively growing urgency and interest in development combined or integrated therapies. This mini-review outlines the rationale for developing new combined therapeutic approaches, and describes the state of the art of the various potential strategies and the promising research perspectives.

Overall survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast cancer: A meta-analysis

2009-11-30

Summary: Background: Taxanes have been extensively tested in patients with advanced breast cancer, but it is unclear whether their weekly use might offer any benefits against standard every three weeks administration. We therefore performed a meta-analysis of randomized controlled trials that compared weekly and every three weeks taxanes regimens in advanced breast cancer.Methods: The endpoints that we assessed were objective response rate, progression free survival (PFS) and overall survival. Efficacy data for paclitaxel and docetaxel were separately analyzed. Trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences.Results: Οbjective response rate was notably better when paclitaxel was used as every three weeks regimen (7 studies, 1772 patients, fixed effect model pooled RR 1.20 95%CI 1.08–1.32 p<0.001). No difference were found for PFS (6 studies, 1610 patients, random effect model HR 1.02, 95%CI 0.81–1.30 p=0.860); while OS was statistically higher among patients receiving weekly paclitaxel (5 studies, 1471 patients, fixed effect model pooled HR 0.78, 95%CI 0.67–0.89 p=0.001). No differences were observed for the weekly compared to the every three weeks use of docetaxel either for objective response, PFS and OS. Overall, the incidence of serious adverse events, neutropenia, neutropenic fever, and peripheral neuropathy were significantly lower in weekly taxanes schedules. The incidence of nail changes and epiphora were significantly lower in the every three weeks docetaxel regimens.Conclusions: Use of paclitaxel in weekly regimen give overall survival advantages compared with the standard every three weeks regimen. The observed survival benefit does not seem to stem from an increased potency of the drug with weekly regimens. The use of weekly paclitaxel regimens is therefore recommended for the treatment of locally advanced/metastatic breast cancer.

Bevacizumab in the treatment of breast cancer

2009-11-23

Summary: Current evidence indicates that angiogenesis plays an important role in the pathogenesis of several malignancies, including breast cancer. Bevacizumab is a monoclonal antibody that targets the vascular endothelial growth factor (VEGF). Recent clinical data have demonstrated that the addition of bevacizumab to first-line chemotherapy improves the progression-free survival (PFS) of patients with advanced breast cancer. This review presents an update on the clinical studies evaluating the role of bevacizumab in combination with chemotherapy, as well as other agents, both in advanced and early disease. Moreover, although no definitive biomarkers have been identified so far, we provide current data regarding potentially useful predictive factors for treatment with bevacizumab. In addition, we review the suggested mechanisms that lead to resistance to VEGF targeted therapies and we present recent data with respect to the toxicity of bevacizumab.

EORTC Elderly Task Force experts’ opinion for the treatment of colon cancer in older patients

2009-11-30

Summary: As a result of an increasing life expectancy, the incidence of colon cancer in the older population is rising. As a consequence oncologists and their older patients commonly face the dilemma of whether or not to give/receive treatment for colon cancer. However, the paucity of large, well conducted prospective trials makes it difficult to provide evidence-based clinical recommendations for these patients. The current evidence supports the safety and efficacy of treatment for colon cancer in fit older patients and demonstrates that treatment outcome can be similar to that of their younger counterparts. However, it should be noted that these data are derived from retrospective studies which are likely to suffer from selection bias. Despite a growing body of data, further work is still needed to establish optimal strategies to care for this special population and prospective specific trials for older colon cancer patients are clearly needed.