Early 7-day supplemental parenteral nutrition improves body composition and muscle strength in hypophagic cancer patients at nutritional risk.

PURPOSE: The international guidelines recommend the use of supplemental parenteral nutrition (SPN) in cancer patients when they are malnourished and hypophagic and where enteral nutrition is not feasible. However, there are limited data on the short-term effects of SPN in this patient population. METHODS: The aim of this bicentric single-arm clinical trial (NCT02828150) was to evaluate the effects of early 7-day SPN on bioimpedance vectorial analysis (BIVA)-derived body composition, handgrip strength (HG), and serum prealbumin (PAB) in 131 hypophagic, hospitalized cancer patients at nutritional risk, with contraindications for enteral nutrition. RESULTS: One hundred eighteen patients (90.1%) completed the 7-day SPN support regimen and 102 of them (86.4%) were in advanced disease stage. SPN induced a significant improvement of phase angle (PhA, + 0.25 [95% CI 0.11, 0.39]; p = 0.001), standardized phase angle (SPA, + 0.33 [95% CI 0.13, 0.53]; p = 0.002), HG (+ 2.1 kg -95% CI 1.30, 2.81]; p < 0.001), and PAB (+ 3.8 mg/dL [95% CI 2.1, 5.6]; p < 0.001). In multivariable analysis, the effects on BIVA parameters were more pronounced in patients (N = 90, 76.3%) in whom estimated protein and calorie requirements were both satisfied (adjusted difference: PhA, + 0.39 [95% CI 0.04, 0.73]; p = 0.030; SPA, + 0.62 [95% CI 0.16, 1.09]; p = 0.009). No significant changes in hydration status were detected and no severe metabolic or other complications occurred. CONCLUSIONS: Early 7-day SPN resulted in improved body composition, HG and PAB levels in hypophagic, and hospitalized cancer patients at nutritional risk in the absence of any relevant clinical complications. Further trials, aimed at verifying the efficacy of this early nutritional intervention on mid- and long-term primary clinical endpoints in specific cancer types, are warranted.

Changes in circulating pro-angiogenic cytokines, other than VEGF, before progression to sunitinib therapy in advanced renal cell carcinoma patients.

OBJECTIVES: This study included a cohort of advanced renal cell carcinoma patients treated with sunitinib. Since resistance to sunitinib may be mediated through angiogenic cytokines other than VEGF, we measured the circulating levels of three pro-angiogenic cytokines: basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin (IL)-6. METHODS: Cytokines were measured at baseline and on the first day of each treatment cycle until progression in 85 advanced kidney cancer patients treated with sunitinib using a quantitative sandwich enzyme immunoassay (ELISA) technique. RESULTS: Even though no statistically significant differences in the titers of the three cytokines were observed between baseline and the time of progression in the whole patient cohort, in 45.3, 46.6, and 37.3% of the patients a more than 50% increase between baseline and the time of progression was shown in circulating IL-6, bFGF, and HGF, respectively. Furthermore, this increase was more than 100% in 37.3, 44, and 30.6% of the patients, respectively. We also demonstrated that, in these patients, cytokines tended to increase and to remain high immediately before progression. CONCLUSIONS: In a large percentage of kidney cancer patients, progression is preceded by a significant increase in pro-angiogenic cytokines other than VEGF.

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

Background: Refractory 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 Methods: Between 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. Results: All 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 (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome. Conclusions: Autologous 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.

Sunitinib in advanced metastatic non-clear cell renal cell carcinoma: a single institution retrospective study.

AIM: Sunitinib is an orally active multi-targeted tyrosine kinase inhibitor that exerts its antitumor effects primarily through the selective inhibition of VEGF. Novel targeted therapies such as sunitinib have transformed the treatment of advanced metastatic renal cell carcinomas, particularly those with clear cell histology. Here, our experience in patients with non-clear cell kidney cancer treated as part of the sunitinib Expanded Access Program is reported. MATERIALS & METHODS: This was a retrospective assessment of 21 patients with non-clear cell renal cell carcinoma who were treated with oral sunitinib 50 mg/day in repeated 6 weekly cycles (4 weeks on and 2 weeks off). Disease assessment and physical examination were recorded at baseline and tumor assessments were performed every 3 months, according to Response Evaluation Criteria In Solid Tumors. The primary outcome measure was progression-free survival. RESULTS: Patients received an average of 6.38 cycles of sunitinib; one patient was classified as a complete responder and two as partial responders. The overall response rate was 14.3% and clinical benefit was attained by 52.4%. The median progression-free survival was 4.1 months while median overall survival was 14.6 months. In general, sunitinib was well tolerated and only three patients experienced a grade 3 toxicity, which resolved with dosage reduction. CONCLUSION: As expected, sunitinib exerted lower antitumor activity in patients with non-clear cell renal cell carcinoma than was achieved in the general population with metastatic kidney cancer. However, responses (one complete and two partial) were documented and clinical benefit was observed in more than half of all patients.

The effect of sorafenib treatment on the diabetic status of patients with renal cell or hepatocellular carcinoma.

AIM: To evaluate the effect of sorafenib on the glucose tolerance and diabetic status of patients with metastatic renal cell carcinoma (RCC) or advanced hepatocellular carcinoma (HCC). MATERIALS & METHODS: Eighty patients with metastatic RCC or advanced HCC received 400 mg sorafenib twice daily for an average of approximately 8 and 5 months, respectively; 22 had diabetes mellitus and three had prediabetes. RESULTS: One of 55 nondiabetic patients, and one of three patients with impaired fasting glucose or impaired glucose tolerance developed diabetes mellitus, one of 12 patients on oral antihyperglycemic agents switched to insulin and no patient treated with insulin needed to increase their dose. CONCLUSION: Sorafenib has the potential to be a feasible and safe treatment option for patients with advanced HCC or metastatic RCC and comorbid diabetes mellitus or prediabetes.

A case report of pulmonary nocardiosis during pembrolizumab: the emerging challenge of the infections on immunotherapy.

The increasing occurrence of infectious complications during immune checkpoint inhibitor (ICI) therapy is an emerging challenge for oncologists. ICIs can reverse T-cell exhaustion, and this may lead to hyperinflammatory dysregulated immunity with subsequent potentially fatal infections. Nocardia spp. are opportunistic pathogens belonging to aerobic Actinomycetes. The authors report a case of Nocardia pneumonia in a 62-year-old male with oral squamous cell carcinoma and lung cancer while taking pembrolizumab. The patient did not take corticosteroids or other immunosuppressant medications. Since ICIs are able to stimulate the immune response, the authors hypothesize that immune reconstitution inflammatory syndrome due to pembrolizumab might cause this opportunistic infection.

The increasing occurrence of infectious complications during immune checkpoint inhibitor (ICI) therapy is an emerging challenge for oncologists. Nocardia spp. typically cause opportunistic infections in immunocompromised patients. An opportunistic infection is an infection caused by pathogens (i.e., bacteria, viruses, fungi and protozoa) in patients with deterioration of the immune system (e.g., due to chemotherapy, malnutrition or radiation therapy). In the past, it was assumed that infections during ICI therapy depended on the immunosuppressant agents (e.g., corticosteroids) used to manage immune-related adverse events occurring during immunotherapy. The authors report a case of Nocardia pneumonia in a 62-year-old male with oral squamous cell carcinoma and lung cancer while taking pembrolizumab. The patient did not take corticosteroids or other immunosuppressant medications. Since ICIs are able to stimulate the immune response, the authors hypothesize that immune reconstitution due to pembrolizumab might have caused an exaggerated inflammatory response, which led to the onset of this infection.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Sequential use of sorafenib and sunitinib in advanced renal-cell carcinoma (RCC): an Italian multicentre retrospective analysis of 189 patient cases.

OBJECTIVE: •To conduct a retrospective, multicentre, cohort analysis to assess the sequential use of the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib. PATIENTS AND METHODS: •Records of 189 patients with renal-cell carcinoma (RCC) who were treated with sorafenib and sunitinib sequentially between March 2004 and April 2009 at 12 Italian study centres were analysed. •Patients were treated under European Expanded Access Programmes or, following market approval, in general clinical practice. •Interventions were sorafenib (800 mg/day) and sunitinib (50 mg every day; 4 weeks on and 2 weeks off). •Progression-free survival (PFS) during treatment with the first and second TKI was evaluated. RESULTS: •In all, 99 patients were treated with sunitinib followed by sorafenib (SuSo) and 90 were treated with sorafenib followed by sunitinib (SoSu); 104 (55%) patients had received prior systemic therapy, mostly with cytokines. •The median (range) PFS on the first TKI was similar between treatment groups [sorafenib 8.4 (1.1-28.9) months; sunitinib 7.8 (0.5-30.4) months; hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.78-1.40, P=0.758]. Multivariate analysis showed that good Memorial Sloan-Kettering Cancer Center status was associated with increased PFS. •After the second TKI, patients in the SoSu group had a longer median PFS than those in the SuSo group (7.9 months vs 4.2 months, respectively; HR 0.54, 95% CI 0.39-0.74, P<0.001). •Multivariate analysis showed only treatment and Eastern Cooperative Oncology Group performance status (and not age, gender, study centre or previous treatment) were significantly associated with duration of PFS. CONCLUSION: •Our findings suggest a limited cross-resistance between sorafenib and sunitinib and that the sequence SoSu may result in a longer combined PFS than SuSo. This is the largest retrospective study to date, though its findings are limited in part by the retrospective nature.

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

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.

The efficacy of immunonutrition in improving tolerance to chemoradiotherapy in patients with head and neck cancer, receiving nutritional counseling: study protocol of a randomized, open-label, parallel group, bicentric pilot study.

BACKGROUND: Nutritional support, including nutritional counseling and oral nutritional supplements (ONSs), has been recommended at the earliest opportunity in head and neck (H&N) cancer patients. The limited available evidence on the efficacy of immunonutrition during chemoradiotherapy (CT-RT) in H&N cancer patients is positive with regard to some secondary endpoints, but is still scanty, particularly with regard to toxicity and treatment tolerance. We hypothesize that early systematic provision of ONSs with a high-protein-high-calorie mixture containing immunonutrients (Impact) compared to standard high-calorie-high-protein nutritional blends, in addition to nutritional counseling, may be beneficial to patients with H&N cancer during CT-RT. Hence, we designed the present study to evaluate the efficacy, in terms of treatment tolerance, toxicity and response, body weight, body composition, protein-calorie intake, quality of life (QoL), fatigue, muscle strength and immunological profile of the early systematic provision of ONSs enriched in immunonutrients compared to isonitrogenous standard blends, in H&N cancer patients undergoing CT-RT. METHODS: This is a pragmatic, bicentric, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial. DISCUSSION: Many efforts are still to be taken to improve the efficacy of nutritional support in oncology. Immunonutrition represents a promising approach also in H&N cancer patients, but the evidence on its efficacy in improving clinical outcomes during CT-RT is still inconclusive. The present pilot study, which guarantees the early provision of nutritional assessment and support to all the enrolled patients in accordance with the recent guidelines and recommendations, could represent one of the first proofs of the clinical effectiveness of early oral immunonutrition in cancer patients undergoing CT-RT and could stimulate further large randomized trials, potentially resulting in the improvement of supportive care quality. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov Identifier: NCT04611113.

Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib.

To identify factors that might predict response to sunitinib in patients with renal cell carcinoma, we measured serum vascular endothelial growth factor (VEGF) and neutrophil gelatinase-associated lipocalin (NGAL) levels. A total of 85 patients were selected and, using the Motzer classification, 46 were assigned to the good- and 38 to the intermediate-risk groups. With univariate Cox analysis, both baseline serum VEGF and NGAL titers, determined by enzyme-linked immunosorbent assay, significantly predicted progression-free survival. For each biomarker, a threshold value was identified, which proved useful to classify patients into groups having titers above or below the thresholds. We then stratified patients according to the two dichotomous variables into good-, intermediate-, and poor-risk groups, and found significantly different progression-free survival rates ranging from 3.5 to 11.6 months. Both VEGF and NGAL maintained their predictive significance at bivariate analysis. Our study shows that serum levels of VEGF and NGAL are significant predictors of progression-free survival in patients with renal cell carcinoma treated with sunitinib.

Sorafenib tosylate in advanced kidney cancer: past, present and future.

The objective of this paper was to review the development of sorafenib tosylate in kidney cancer. The MedLine database, the Proceedings of the Annual American Society of Clinical Oncology meeting, as well as those of other key international meetings were extensively searched to identify relevant publications. Furthermore, the authors' direct experience with the drug was taken into account when commenting on the results retrieved. Sorafenib is a multikinase inhibitor that targets VEGF and PDGF receptors, other kinases, as well as the serine-threonine kinase Raf. Following early signs of activity from phase I and II studies, it has been shown to improve survival of pretreated advanced kidney cancer patients within a placebo-controlled, randomized, phase III trial, leading to its approval both in the United States and in Europe. Its activity has been subsequently confirmed in a real-world population by two expanded access programs performed globally, but not in a first-line setting; it also proved to be non-cross-resistant with two other molecularly targeted agents. Finally, its toxicity profile, which is acceptable and highly predictable, makes sorafenib appealing for combination treatments, especially with other molecularly targeted agents. Despite having been already demonstrated to be active in kidney cancer, the exact role of sorafenib in the first-line setting, in patients who have failed other molecularly targeted agents, and especially in combination with other agents, deserves further, prospective, studies.

Use of sorafenib in two metastatic renal cell cancer patients with end-stage renal impairment undergoing replacement hemodialysis.

Patients with renal cell carcinoma (RCC) may exhibit renal impairment as a more or less direct consequence of their primary disease. Renal impairment may become a severe complication and alter the normal pharmacokinetic and pharmacodynamic behavior of treatment drugs, thus increasing the risk of side effects. We will discuss the cases of two advanced RCC patients with end-stage renal impairment submitted to dialysis who were treated with sorafenib tosylate in our center. Our experience confirms the scarce literature data available so far that indicate that sorafenib can be used in patients undergoing dialysis. Dialysis cannot be considered per se a contraindication to sorafenib therapy, which can be effective. However, patients must be carefully selected and monitored, since sorafenib administration unquestionably increases the risk of side effects in patients affected by several conditions.

Electrochemotherapy of superficial tumors - Current status:: Basic principles, operating procedures, shared indications, and emerging applications.

Treatment of superficial tumors with electrochemotherapy (ECT) has shown a steep rise over the past decade and indications range from skin cancers to locally advanced or metastatic neoplasms. Based on reversible electroporation, which is a physical method to achieve transient tumor cell membrane permeabilization by means of short electric pulses, ECT increases cellular uptake of bleomycin and cisplatin and their cytotoxicity by 8,000- and 80-fold, respectively. Standard operating procedures were established in 2006 and updated in 2018. Ease of administration, patient tolerability, efficacy across histotypes, and repeatability are peculiar advantages, which make standard ECT (ie, ECT using fixed-geometry electrodes) a reliable option for controlling superficial tumor growth locally and preventing their morbidity. Consolidated indications include superficial metastatic melanoma, breast cancer, head and neck skin tumors, nonmelanoma skin cancers, and Kaposi sarcoma. In well-selected patients with oropharyngeal cancers, ECT ensures appreciable symptom control. Emerging applications include skin metastases from visceral or hematological malignancies, vulvar cancer, and some noncancerous skin lesions (keloids and capillary vascular malformations). Repeatability and integration with other oncologic therapies allow for consolidation of response and sustained tumor control. In this review, we present the basic principles of ECT, recently updated operating procedures, anesthesiological management, and provide a synthesis of the efficacy of standard ECT across histotypes.

Immunological stress in kidney cancer patients undergoing either open nephrectomy or nephron-sparing surgery: an immunophenotypic study of lymphocyte subpopulations and circulating dendritic cells.

Immunosuppression is a characteristic hallmark of renal cell carcinoma (RCC), with several complex immune defects, almost solely at the level of cell-mediated immune function, well evident even in patients at first diagnosis. The main circulating lymphocyte subsets and the total number of circulating dendritic cells were quantified in 47 RCC patients at diagnosis (T0), 12 h (T1), 24 h (T2) and 8 days following either radical nephrectomy or nephron-sparing surgery using flow cytometry. RCC patients presented, at baseline, (T0) a profound state of immunosuppression involving naïve T-cells, memory T-cells, CD16+ NK and total circulating dendritic cells, that worsened after 12 (T1) and 24 h (T2) from surgery, involving the majority of the analysed subsets; after 8 days (T3) from surgical removal of tumor, however, there was a return of all the analyzed parameters to the basal state. In conclusion, surgery causes transient but relevant immune suppression in RCC patients; even though, by day +8, this tends to return to baseline, immunostimulatory therapies could be considered in the peri-operative setting with the aim of reducing immunosuppression and, hopefully, also disease recurrence.

Nutritional counseling with or without systematic use of oral nutritional supplements in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: To evaluate the benefit of oral nutritional supplements (ONS) in addition to nutritional counseling in head and neck cancer (HNC) patients undergoing radiotherapy (RT). METHODS: In a single-center, randomized, pragmatic, parallel-group controlled trial (ClinicalTrials.gov: NCT02055833; February 2014-August 2016), 159 newly diagnosed HNC patients suitable for to RT regardless of previous surgery and induction chemotherapy were randomly assigned to nutritional counseling in combination with ONS (N = 78) or without ONS (N = 81) from the start of RT and continuing for up to 3 months after its end. Primary endpoint was the change in body weight at the end of RT. Secondary endpoints included changes in protein-calorie intake, muscle strength, phase angle and quality of life and anti-cancer treatment tolerance. RESULTS: In patients with the primary endpoint assessed (modified intention-to-treat population), counseling plus ONS (N = 67) resulted in smaller loss of body weight than nutritional counseling alone (N = 69; mean difference, 1.6 kg [95%CI, 0.5-2.7]; P = 0.006). Imputation of missing outcomes provided consistent findings. In the ONS-supplemented group, higher protein-calorie intake and improvement in quality of life over time were also observed (P < 0.001 for all). The use of ONS reduced the need for changes in scheduled anti-cancer treatments (i.e. for RT and/or systemic treatment dose reduction or complete suspension, HR=0.40 [95%CI, 0.18-0.91], P = 0.029). CONCLUSION: In HNC patients undergoing RT or RT plus systemic treatment, and receiving nutritional counseling, the use of ONS resulted in better weight maintenance, increased protein-calorie intake, improved quality of life and was associated with better anti-cancer treatment tolerance.

Renal cell carcinoma-induced immunosuppression: an immunophenotypic study of lymphocyte subpopulations and circulating dendritic cells.

BACKGROUND: Renal cell carcinoma (RCC)-induced immune dysfunction in patients at first diagnosis was investigated. PATIENTS AND METHODS: The main circulating lymphocyte subsets, the total number of circulating and intratumor dendritic cells and the titers of circulating VEGF were quantified in 47 RCC patients, using flow cytometric, immunohistochemical and ELISA assays. RESULTS: Despite a significant activation of CD3/HLA-DR+ lymphocytes and of the CD56+ NK subset, RCC patients presented a marked immunosuppression of CD4/CD45RA naïve T-cells, CD4/CD45RO memory T-cells, CD16+ NK-cells, and total circulating dendritic cells, as well as a significant increase of lymphocytes co-expressing the CD4 and CD8 antigens. Finally, CD16+/CD56+ NK and DCs were poorly represented in tumor specimens. CONCLUSION: The complex immunological dysfunctions demonstrated involve different levels of immunocompetence and indicate a pattern of major disturbance of the immune system.

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.