Cancer Treatment Reviews

Editorial Board

2012-06-01

Brain metastases from renal cell carcinoma. Should we change the current standard?

Jordi Remon, Pilar Lianes, Susana Martínez — 2011-07-18

Abstract: Renal cell carcinoma (RCC) is one of the most common sources of brain metastases, with an incidence that varies widely from 4% to 48% according to different studies. In addition, asymptomatic metastases occur in up to 33% of patients with metastatic RCC, further complicating the decision-making process in this poor prognosis population. The purpose of this review is to cover in depth the present state of knowledge on the diagnosis and management of patients with brain metastases from RCC, in order to assess whether the current standard should be challenged. The existing systems to predict response and survival will be reviewed, as well as the available therapeutic options regarding local treatment and systemic therapy, all within the context of updated data from clinical trials. In this regard, the role of novel targeted agents for the treatment of brain metastases from RCC, such as the multi-targeted receptor tyrosine kinase inhibitors sunitinib and sorafenib, will be updated and discussed.

Cyto-reductive Surgery combined with Hyperthermic Intra-Peritoneal Chemotherapy for Peritoneal Surface Malignancies: Current treatment and results

Antonio Sommariva, Pierluigi Pilati, Carlo Riccardo Rossi — 2011-08-02

Abstract: Cyto-reductive Surgery (CS) combined with Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) as loco-regional treatment of Peritoneal Surface Malignancies (PSM) has increasingly gained acceptance in clinical practice. This review summarizes the more relevant studies on this topic. Indications, pre-operative work-up, technical aspects, outcome and future directions of this combined approach in the treatment of Peritoneal Surface Malignancies are discussed here and proposed in an informative and didactic manner.

Breast reconstruction: à la carte not table d’hote

Ian S. Fentiman, Jian Farhadi — 2011-11-24

Abstract: NICE guidelines emphasise the need for breast cancer patients undergoing mastectomy to be offered all appropriate options for immediate reconstruction. In the majority of hospitals this is not happening. Patients are being offered the reconstruction technique for which their surgeon has been trained and many never meet an oncoplastic surgeon to discuss the wide range of options that are available. This means that many have sub-optimal reconstructions often using implants that may need to be subsequently replaced and are incompatible with post-operative radiotherapy. Patients will be better served by a few high throughput, high quality centres specialising in tailoring the right reconstruction for the woman who needs a mastectomy rather than the present system of having reconstruction of variable quality available ubiquitously.

Targeting angiogenesis in ovarian cancer

Jordan Schmitt, Daniela Matei — 2011-07-18

Abstract: Results of standard chemotherapy in ovarian cancer are hampered by the development of drug resistance leading to disease recurrence. This prompted interest in the development of therapies targeting critical pathways responsible for tumor progression. Angiogenesis is a key process that enables ovarian cancer growth and metastasis in the peritoneal space. Its regulation relies on signaling mechanisms initiated by the vascular endothelial growth factor, the platelet-derived growth factor, the fibroblast growth factor, angiopoietins, and others. These pathways are not only important to the modulation of the tumor microenvironment and vasculature, but also control cancer cell proliferation and survival. In this review, we discuss preclinical evidence supporting the rationale for inhibiting these pathways and provide an overview for the clinical development of agents targeting them. Clinical trials evaluating such agents alone and in combination with chemotherapy are ongoing. Early clinical results position antiangiogenic therapy at the forefront of change to the standard treatment of difficult to treat ovarian cancer.

Skeletal metastasis in renal cell carcinoma: Current and future management options

Steven L. Wood, Janet E. Brown — 2011-08-01

Abstract: Metastasis to the skeleton is common in advanced renal cancer and leads to debilitating skeletal complications including severe pain, increased fracture rate and spinal cord compression. The incidence of renal cell carcinoma is increasing by around 2% per year and recent advances in targeted anti-angiogenic therapy for advanced disease are expected to lead to longer survival times. The clinical management of metastatic bone disease in renal cell carcinoma therefore merits greater focus than hitherto. Bone metastases arising from renal cancer are highly osteolytic and particularly destructive. Fortunately, the continuing development of anti-resorptive drugs is revolutionising the medical management of metastatic bone disease across many tumour types and making a major impact on quality of life. The bisphosphonate zoledronic acid is now licensed for use in advanced renal cell carcinoma and appears to yield a greater benefit in terms of reduction in skeletal related events than in bone metastases arising from other tumour types. Drugs which are directed at specific targets in the bone metastasis pathway are in development, including denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor kappa B ligand, which has recently been licensed in the United States for use in renal cell carcinoma, with European licensing expected soon. This review examines the increasing options for treatment of metastatic bone disease in renal cell carcinoma, with a focus on drug-based advances and progress in the development of existing and new biomarkers to support clinical management.

The role of the insulin-like growth factor signaling pathway in non-small cell lung cancer and other solid tumors

Giorgio V. Scagliotti, Silvia Novello — 2011-09-12

Abstract: The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have become increasingly recognized as having a driving role in the development of malignancy, and consequently IGF-1R has become a potential target for cancer therapy. Several inhibitors of IGF-1R are in clinical development for the treatment of solid tumors, including non-small cell lung cancer (NSCLC). These IGF-1R-targeted agents include monoclonal antibodies such as cixutumumab (IMC-A12), AMG-479, AVE1642, BIIB022, dalotuzumab (MK-0646), and robatumumab (Sch717454), the ligand neutralizing antibody Medi-573, and the small molecule inhibitors BMS-754807, linsitinib (OSI-906), XL228, and AXL1717. Two phase III trials of the anti-IGF-1R monoclonal antibody, figitumumab (CP-751,871), were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints. In light of disappointing clinical data with figitumumab and other targeted agents, it is likely that the use of molecular markers will become important in predicting response to treatment. This review outlines the role of IGF-1R signaling in solid tumors with a particular focus on NSCLC, and provides an overview of clinical data.

New drugs for breast cancer subtypes: Targeting driver pathways to overcome resistance

Giuseppe Curigliano — 2011-07-18

Abstract: Breast cancer is not a single disease. Genetic array tools can define several subtypes. Specific biological processes and distinct gene pathways are associated with prognosis and sensitivity to chemotherapy and targeted agents in different subtypes of breast cancers. As a consequence, breast cancer can be classified by molecular events. A primary challenge for future drug development in breast cancer will be to distinguish genes and pathways that “drive” cancer proliferation (drivers) from genes and pathways that have no role in the development of cancer (passengers). The identification of functional pathways that are enriched for mutated genes will select sub-population of patients the will most likely be sensitive to biology driven targeted agents. The selection of driver pathways in resistant tumors will permit to discover a biology-driven platform for new drug development to overcome resistance. Any of the breast cancer subtypes implies that clinicians should consider cases within the various distinct sub-population in order to properly choose the most personalized therapeutic approach. We will review all new emerging agents targeting the driver pathways within breast cancer molecular subtypes.

Emerging therapies for urothelial cancer

2011-11-23

Abstract: Urothelial carcinoma is one of the leading causes of death in Europe and the United States. Despite its chemosensitivity, median overall survival for advanced disease is still nearly 1year. Most second-line chemotherapeutic agents tested have been disappointing. Thus, new treatment strategies are clearly needed. This review focuses on emerging therapies in urothelial carcinoma. Results from recent clinical trials, investigating the activity of new generation cytostatic agents, as well as results from studies assessing the toxicity and efficacy of novel targeted therapies, are discussed. In this setting, anti-epidermal growth factor receptor, angiogenesis, and phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors account for the majority of phase I and II trials.

Endometrial cancer and venous thromboembolism in women under age 50 who take tamoxifen for prevention of breast cancer: A systematic review

2011-07-21

Abstract: Background: Breast cancer prevention with tamoxifen in high-risk women is limited due to concerns of endometrial cancer and thromboembolism. We report the risk of endometrial cancer, deep vein thrombosis and pulmonary embolism in women <50years given tamoxifen for breast cancer prevention.Methods: We searched the Cochrane Central Register of Controlled Trials and National Library of Medicine for published data from January 1970 to December 2010. We contacted principal investigators of clinical trials, and searched Grey literature and conference proceedings for unpublished data. We reviewed three breast cancer prevention trials comparing tamoxifen (20mg per day) with placebo for five years in high-risk women <50years. The absolute risk and relative risk (RR) for each outcome were estimated.Results: The RR for endometrial cancer in women <50years given tamoxifen is 1.19 (95% CI, 0.53–2.65; p=0.6) as compared to the placebo. The RR for deep vein thrombosis with tamoxifen is 2.30 (95% CI, 1.23–4.31; p=0.009) in the active phase of treatment. The risk decreases to 1.00 (95% CI, 0.38–2.67; p=0.9) in the follow-up phase. The RR for pulmonary embolism with tamoxifen is 1.16 (95% CI, 0.55–2.43; p=0.6).Interpretation: The risk of endometrial cancer, deep vein thrombosis and pulmonary embolism is low in women <50years who take tamoxifen for breast cancer prevention. The risk decreases from the active to follow-up phase of treatment. Education and counseling are the cornerstones of breast cancer chemoprevention.