Immunological Effects of Multikinase Inhibitors for Kidney Cancer: A Clue for Integration with Cellular Therapies?

The multikinase inhibitors Sunitinib and Sorafenib not only inhibit angiogenesis and tumor growth, but also have the potential of interacting with the function of the immune system

Safety and treatment patterns of multikinase inhibitors in patients with metastatic renal cell carcinoma at a tertiary oncology center in Italy

<p>Abstract</p> <p>Background</p> <p>Multikinase inhibitors (MKIs) sunitinib and sorafenib have become a standard of care for metastatic renal cell carcinoma (mRCC). This study assessed safety and treatment patterns for these agents in a real-world clinical practice setting in Italy.</p> <p>Methods</p> <p>A retrospective medical record review was performed at a tertiary oncology center in Italy. The study included MKI-naïve non-trial patients ≥18 years old, with a histological diagnosis of mRCC, and who received sunitinib or sorafenib as first MKI during 9/2005-7/2008. Data were collected on adverse events (AEs), treatment modifications (discontinuations, interruptions, dose changes), and reasons for these modifications.</p> <p>Results</p> <p>145 patients were included; 85 received sunitinib and 60 received sorafenib as first-line MKI. Median treatment duration was 6.6 (sunitinib) and 5.8 (sorafenib) months. 97.6% and 70.0% of patients receiving sunitinib and sorafenib, respectively, experienced ≥1 AE; 27.1% and 31.7% had ≥1 grade 3/4 AE. The most common any grade AE for sunitinib was fatigue/asthenia (81.2%), followed by mucositis/stomatitis (58.8%) and decreased taste sensation (42.4%), while for sorafenib this was fatigue/asthenia (43.3%) followed by hand-foot syndrome (38.3%) and diarrhea (31.7%). Treatment discontinuation, interruption, and dose reduction due to AEs occurred in 11.8%, 23.5%, and 30.6%, respectively, of patients receiving sunitinib, and 5.0%, 23.3%, and 36.7%, respectively, of patients receiving sorafenib.</p> <p>Conclusions</p> <p>In this retrospective study, most patients experienced ≥1 AE during first-line MKI treatment. AEs were reported frequently and resulted in treatment modifications in 40% of patients receiving sunitinib and 45% of patients receiving sorafenib. These results suggest a need for additional effective and more tolerable treatments for mRCC.</p

Influence of different lipid emulsions on specific immune cell functions in head and neck cancer patients receiving supplemental parenteral nutrition: An exploratory analysis.

Abstract Objectives The effect of diet on immune responses is an area of intense investigation. Dietary lipids have been shown to differently influence and fine-tune the reactivity of immune cell subsets, thus potentially affecting clinical outcomes. Patients with head and neck squamous cell carcinoma face malnutrition, due to swallowing impairment related to the tumor site or to treatment sequalae, and may need supplemental parenteral nutrition (SPN) in addition to oral feeding when enteral nutrition is not feasible. Additionally, immune depression is a well-known complication in these patients. Parenteral nutrition (PN) bags contain amino acids, minerals, electrolytes and mostly lipids that provide calories in a concentrated form and are enriched with essential fatty acids. The aim of this study was to investigate multiple parameters of the immune responses in a cohort of patients with head and neck squamous cell carcinoma undergoing supplemental PN with bags enriched in ω-3 or ω-9 and ω-6 fatty acids. Methods To our knowledge, this was the first exploratory study to investigate the effects of two different PN lipid emulsions on specific immune cells function of patients with advanced head and neck squamous carcinoma. ω-3-enriched fish-oil-based- and ω-6- and ω-9-enriched olive-oil-basedSPN was administered to two groups of patients for 1 wk in the context of an observational multicentric study. Polychromatic flow cytometry was used to investigate multiple subsets of leukocytes, with a special focus on cellular populations endowed with antitumor activity. Results Patients treated with olive-oil-based PN showed an increase in the function of the innate (natural killer cells and monocytes) and adaptive (both CD4 and CD8 cells) arms of the immune response. Conclusion An increase in the function of the innate and adaptive arms of the immune response may favor antitumoral responses

Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma

BackgroundRefractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.Patients and MethodsBetween 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.ResultsAll patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (&lt;3 disease sites), and plasma EBV-DNA &lt;1000 copies/mL had a better outcome.ConclusionsAutologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial

Oncology is changing: the challenge of effectively assessing response within clinical trials in low-grade gliomas

The current WHO classification of primary central nervous system (CNS) tumors recognizes four separate tumor grades (I–IV), which can be grouped into low-grade (I and II) or high-grade (III and IV), depending on the absence or presence of high-grade histopathological features, such as microvascular proliferation and necrosis..

Oncology is changing: the challenge of effectively assessing response within clinical trials in low-grade gliomas

The current WHO classification of primary central nervous system (CNS) tumors recognizes four separate tumor grades (I–IV), which can be grouped into low-grade (I and II) or high-grade (III and IV), depending on the absence or presence of high-grade histopathological features, such as microvascular proliferation and necrosis..

Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC) incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs), chronic kidney diseases (also dialysis and transplantation), as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL), Hereditary Papillary Renal Carcinoma (HPRC), Birt-Hogg-Dubé Syndrome (BHD), and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC

Cytokine-Based Immunotherapy for Advanced Kidney Cancer: Past Results and Future Perspectives in the Era of Molecularly Targeted Agents

Until recently, immunotherapy has been the only therapeutic option available for patients with advanced kidney cancer, even though different choices were often made on the two sides of the Atlantic Ocean. The absence of alternatives made different immunotherapeutic approaches common practice, even with few adequate randomized studies that addressed key questions, such as the best treatment and schedule, and so on. The recent registration of the first two, molecularly targeted, agents Sorafenib and Sunitinib could (and will) render many therapeutic approaches, e.g., single-agent Interferon, obsolete. In this review, we shall cover the past achievements obtained so far with cytokine-based immunotherapy and discuss the present role of immunotherapy in the era of molecularly targeted agents. In particular, specific indications for immunotherapy are emerging (e.g., the use of Interleukin-2 in patients with high CAIX expression), while new trials are ongoing to test immunotherapy in combination with molecularly targeted agents, such as Sorafenib, Sunitinib, or Bevacizumab