Factors affecting the unexpected failure of DCE-MRI to determine the optimal biological dose of the vascular targeting agent NGR-hTNF in solid cancer patients

13052 Background: NGRhTNF is a vascular targeting agent (VTA) exploiting a tumour homing peptide (CNGRCG) selectively binding solid tumor (lung, renal, and colorectal) neovasculature. NGRhTNF specific binding relies on dynamic interactions with TNF-receptors, aminopeptidase N (CD13) and a specific integrin: a combination of receptors expressed by the tumor neovasculature endothelium, but not on normal vessels. This combination provides NGRhTNF with unique biological properties: at low dose, increased tumor vascular permeability, and massive tumor necrosis at high dose. Mouse preclinical data confirmed these properties, revealing also strong synergy between low dose NGRhTNF and cytotoxic agents (antracyclines, platinum based compounds, etc.). Methods: Based on these data, a series of studies were designed. A multicentre phase I study with NGRhTNF as single agent -still in progress- aims at defining MTD and preliminary anticancer activity, within the EORTC network (EORTC 16041). A single center phase I study exploiting the low dose range (0.2–1.6 μg/m2) aims at defining safety and NGRhTNF activity on the tumor vascular permeability using DCE MRI (HSR NGR002). Results: Twelve advanced neoplastic patients were enrolled in the HSR NGR002 study. Up to the dose of 1.6 μg/m2, the only common toxicity was represented by constitutional symptoms such as infusion-associated chills (40%) of mild to moderate intensity. At the tested doses, NGRhTNF increased vascular permeability, as shown by changes in DCE MRI parameters (Ktrans and Kep), and modulated the expression of chemokines possessing antiangiogenic activity. NGRhTNF achieved stable disease in about 45% of highly refractory treated patients, and still ongoing long lasting disease control in 2 cases (7 and 9 months along with sharp decline of CA125 and VEGF). Conclusions: NGR-hTNF, a VTA with a unique mechanism of action, combines activity on tumor vascular permeability and direct anti-cancer effect. Preliminary data in humans confirm its favourable safety profile along with remarkable anticancer activity, thus rendering the agent suitable for a development program alone or in combination with chemotherapeutics. Phase II low dose combination studies will begin in 2006. [Table: see text]

Download Full-text

Defining the optimal biological dose of NGR-hTNF, a selective vascular targeting agent, in advanced solid tumours

European Journal of Cancer ◽

10.1016/j.ejca.2009.10.005 ◽

2010 ◽

Vol 46 (1) ◽

pp. 198-206 ◽

Cited By ~ 40

Author(s):

Vanesa Gregorc ◽

Giovanni Citterio ◽

Giordano Vitali ◽

Anna Spreafico ◽

Paola Scifo ◽

...

Keyword(s):

Solid Tumours ◽

Vascular Targeting ◽

Biological Dose ◽

Vascular Targeting Agent

Download Full-text

Comparison of Cancer Patients to Non-Cancer Patients among COVID-19 Inpatients at a National Level

Cancers ◽

10.3390/cancers13061436 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1436

Author(s):

Alain Bernard ◽

Jonathan Cottenet ◽

Philippe Bonniaud ◽

Lionel Piroth ◽

Patrick Arveux ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Mortality Risk ◽

Hospital Admissions ◽

National Level ◽

Administrative Database ◽

Hospital Death ◽

Solid Cancer ◽

Hematological Cancer ◽

Risk Of Death

(1) Background: Several smaller studies have shown that COVID-19 patients with cancer are at a significantly higher risk of death. Our objective was to compare patients hospitalized for COVID-19 with cancer to those without cancer using national data and to study the effect of cancer on the risk of hospital death and intensive care unit (ICU) admission. (2) Methods: All patients hospitalized in France for COVID-19 in March–April 2020 were included from the French national administrative database, which contains discharge summaries for all hospital admissions in France. Cancer patients were identified within this population. The effect of cancer was estimated with logistic regression, adjusting for age, sex and comorbidities. (3) Results: Among the 89,530 COVID-19 patients, we identified 6201 cancer patients (6.9%). These patients were older and were more likely to be men and to have complications (acute respiratory and kidney failure, venous thrombosis, atrial fibrillation) than those without cancer. In patients with hematological cancer, admission to ICU was significantly more frequent (24.8%) than patients without cancer (16.4%) (p < 0.01). Solid cancer patients without metastasis had a significantly higher mortality risk than patients without cancer (aOR = 1.4 [1.3–1.5]), and the difference was even more marked for metastatic solid cancer patients (aOR = 3.6 [3.2–4.0]). Compared to patients with colorectal cancer, patients with lung cancer, digestive cancer (excluding colorectal cancer) and hematological cancer had a higher mortality risk (aOR = 2.0 [1.6–2.6], 1.6 [1.3–2.1] and 1.4 [1.1–1.8], respectively). (4) Conclusions: This study shows that, in France, patients with COVID-19 and cancer have a two-fold risk of death when compared to COVID-19 patients without cancer. We suggest the need to reorganize facilities to prevent the contamination of patients being treated for cancer, similar to what is already being done in some countries.

Download Full-text

Corticosteroid administration for cancer-related indications is an unfavorable prognostic factor in solid cancer patients receiving immune checkpoint inhibitor treatment

International Immunopharmacology ◽

10.1016/j.intimp.2021.108031 ◽

2021 ◽

Vol 99 ◽

pp. 108031

Author(s):

Ying Wang ◽

Mengxue Yang ◽

Mingyang Tao ◽

Peipei Liu ◽

Cheng Kong ◽

...

Keyword(s):

Prognostic Factor ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Solid Cancer ◽

Corticosteroid Administration ◽

Unfavorable Prognostic Factor ◽

Inhibitor Treatment

Download Full-text

The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920980546 ◽

2020 ◽

Vol 12 ◽

pp. 175883592098054

Author(s):

Huilin Xu ◽

Ximing Xu ◽

Wei Ge ◽

Jinju Lei ◽

Dedong Cao

Keyword(s):

Adverse Events ◽

Cancer Patients ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Good Survival ◽

Solid Cancer ◽

Cancer Type ◽

Early Effect ◽

Overall Response

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

Download Full-text

Increased Hospitalization and Mortality from COVID-19 in Prostate Cancer Patients

Cancers ◽

10.3390/cancers13071630 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1630

Author(s):

Dimple Chakravarty ◽

Parita Ratnani ◽

Stanislaw Sobotka ◽

Dara Lundon ◽

Peter Wiklund ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Mortality Rates ◽

Mount Sinai Hospital ◽

Solid Cancer ◽

Continuous Variables ◽

Breast Cancer Patients ◽

Chi Square ◽

Hospital System ◽

Tumor Types

Background: Cancer patients with COVID-19 have a poor disease course. Among tumor types, prostate cancer and COVID-19 share several risk factors, and the interaction of prostate cancer and COVID-19 is purported to have an adverse outcome. Methods: This was a single-institution retrospective study on 286,609 patients who underwent the COVID-19 test at Mount Sinai Hospital system from March 2020 to December 2020. Chi-square/Fisher’s exact tests were used to summarize baseline characteristics of categorical data, and Mann–Whitney U test was used for continuous variables. Univariable logistic regression analysis to compare the hospitalization and mortality rates and the strength of association was obtained by the odds ratio and confidence interval. Results: This study aimed to compare hospitalization and mortality rates between men with COVID-19 and prostate cancer and those who were COVID-19-positive with non-prostate genitourinary malignancy or any solid cancer, and with breast cancer patients. We also compared our studies to others that reported the incidence and severity of COVID-19 in prostate cancer patients. Our studies highlight that patients with prostate cancer had higher susceptibility to COVID-19-related pathogenesis, resulting in higher mortality and hospitalization rates. Hospitalization and mortality rates were higher in prostate cancer patients with COVID-19 when compared with COVID-19 patients with non-prostate genitourinary (GU) malignancies.

Download Full-text