scholarly journals A phase 2a clinical study on the safety and efficacy of individualized dosed mebendazole in patients with advanced gastrointestinal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Mansoori ◽  
M. Fryknäs ◽  
C. Alvfors ◽  
A. Loskog ◽  
R. Larsson ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Gastrointestinal Cancer ◽  
Progressive Disease ◽  
Treatment Phase ◽  
Efficacy And Safety ◽  
Safety And Efficacy ◽  
Anticancer Effects ◽  
Experimental Cancer ◽  
Cancer Models ◽  
Clinical Surveillance

AbstractMebendazole is used extensively for treatment of local gut helminthic and invasive echinococcus infections. Anticancer effects of mebendazole have been shown in experimental cancer models and in case studies in patients with advanced cancer. Given these observations, the aims of this study were to investigate safety and efficacy of individualized dosed mebendazole in the cancer indication. Patients with treatment refractory gastrointestinal cancer were treated with individualized dose adjusted mebendazole up to 4 g/day to target a serum concentration of 300 ng/ml. Efficacy and safety were assessed by CT-scans, clinical surveillance and blood sampling. Eleven patients were included in the study and 10 started the treatment phase. Two patients stopped treatment prior to and the remaining eight after tumour evaluation by CT-scan at 8 weeks, all due to progressive disease. Four patients also fulfilled criteria suggested for hyperprogression. Only five patients reached the target serum-mebendazole concentration. No severe adverse effects were observed. Individualized dose adjusted mebendazole is safe and well tolerated in patients with advanced cancer but all patients experienced rapid progressive disease. New approaches such as prodrug development and combination with other anticancer drugs seem needed for further exploration of mebendazole as an anticancer drug.

Efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC) and brain metastases: Preliminary results from the GETUG-AFU 26 (Nivoren) study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4563-4563 ◽  
Author(s):  
Bernard J. Escudier ◽  
Sylvie Chabaud ◽  
Delphine Borchiellini ◽  
Gwenaelle Gravis ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Progressive Disease ◽  
Objective Response ◽  
Previous Treatment ◽  
Efficacy And Safety ◽  
Pivotal Phase ◽  
Safety And Efficacy ◽  
Prospective Phase ◽  
Brain Ct Scan ◽  
Previously Treated

4563 Background: Nivolumab (N) has been shown active in patients (pts) with mRCC after failure of 1 or 2 TKIs. Efficacy and safety of N in pts with brain metastases (BM) from RCC is still unknown. The aim of this study is to report preliminary data of the Nivoren study in pts with BM. Methods: GETUG-AFU 26 (Nivoren) is a prospective phase 2 study assessing safety and efficacy of N in a broader mRCC patient population than those recruited in the pivotal phase 3, including pts with BM (previously treated or not, but not requiring steroids), with previous mTOR inhibitor, with PS 2 as well as in previously highly pretreated pts. N was given every 2 weeks at 3mg/kg, until disease progression or unacceptable toxicity. Treatment was allowed beyond progression in case of clinical benefit. All pts had brain CT scan or MRI at baseline. Results: Up to December 2016 , 588 pts have been enrolled including 55 pts with BM (35 (67%) ,6 (12%) and 11 (21%) with 1, 2 or > 2 BM, respectively. Of those 55 pts, 10 pts (23%) were PS 2 and 25 (58%) PS 1, and 16 patients (29%) had received more that 2 lines of therapy. No previous treatment for BM was performed in 67% (n = 37), while 9% had previous brain surgery (n = 5 ;) or brain radiation (n = 17 (31%). 2/55 pts never received N. Median duration of therapy in BM pts was 2.4 months (varying from 0 to 9) with a 3-months PFS of 60% (IC95% = 45 – 73). Median OS is not reached at the time of this analysis. Among 44 pts with assessment of response on BM, 10 (23%) had objective response while 21 (48%) had local progressive disease. Neurologic deterioration requiring steroids was observed in 15 pts (32%) . Updated data will be presented at the meeting. Conclusions: This is the first large study to report preliminary safety and efficacy of N in RCC pts with BM. Safety of N in this pt population appears to be acceptable, although some pts do require steroids because of brain progressive disease. Objective response in the brain was observed in 23% of pts. Further follow up is required to determine the real benefit of N in this group of mRCC pts. Clinical trial information: NCT03013335.

Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer

2020 ◽  
Author(s):  
S Leyvraz ◽  
J Berlin ◽  
DS Hong ◽  
J Deeken ◽  
V Boni ◽  
...  
Keyword(s):  
Gastrointestinal Cancer ◽  
Efficacy And Safety

scholarly journals Safety and Efficacy of Weekly Paclitaxel and Cisplatin Chemotherapy for Ovarian Cancer Patients with Hypersensitivity to Carboplatin

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 640
Author(s):  
Shinichi Tate ◽  
Kyoko Nishikimi ◽  
Ayumu Matsuoka ◽  
Satoyo Otsuka ◽  
Makio Shozu
Keyword(s):  
Ovarian Cancer ◽  
Progressive Disease ◽  
Renal Toxicity ◽  
Progression Free Survival ◽  
Median Number ◽  
Weekly Paclitaxel ◽  
Peritoneal Carcinoma ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Carboplatin Hypersensitivity

Background: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). Methods: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2; cisplatin 25 mg/m2; 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). Results: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3–7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95% CI: 19.0–50.2), respectively. Conclusions: wTP was safe and well-tolerated in patients who developed carboplatin HSR.

scholarly journals Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA–PEG nanoparticles

BioMetals ◽  
2021 ◽  
Author(s):  
Alessio Menconi ◽  
Tiziano Marzo ◽  
Lara Massai ◽  
Alessandro Pratesi ◽  
Mirko Severi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gold Complex ◽  
Drug Candidate ◽  
Side Reactions ◽  
Anticancer Effects ◽  
Cancer Models ◽  
Free Gold ◽  
Hct 116 ◽  
New Formulation

AbstractChloro(triethylphosphine)gold(I), (Et3PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et3PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et3PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et3PAuCl was encapsulated in biocompatible PLGA–PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et3PAuCl (nano-Et3PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et3PAuCl, was clearly documented. The implications of these findings are discussed.

scholarly journals Fucoxanthin and Colorectal Cancer Prevention

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2379
Author(s):  
Masaru Terasaki ◽  
Atsuhito Kubota ◽  
Hiroyuki Kojima ◽  
Hayato Maeda ◽  
Kazuo Miyashita ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Brown Algae ◽  
Lifestyle Modification ◽  
Signal Pathways ◽  
Potential Candidate ◽  
Anticancer Effects ◽  
Cancer Models ◽  
Candidate Drug ◽  
Colorectal Cancer Prevention ◽  
Dietary Carotenoid

Colorectal cancer (CRC), which ranks among the top 10 most prevalent cancers, can obtain a good outcome with appropriate surgery and/or chemotherapy. However, the global numbers of both new cancer cases and death from CRC are expected to increase up to 2030. Diet-induced lifestyle modification is suggested to be effective in reducing the risk of human CRC; therefore, interventional studies using diets or diet-derived compounds have been conducted to explore the prevention of CRC. Fucoxanthin (Fx), a dietary carotenoid, is predominantly contained in edible brown algae, such as Undaria pinnatifida (wakame) and Himanthalia elongata (Sea spaghetti), which are consumed particularly frequently in Asian countries but also in some Western countries. Fx is responsible for a majority of the anticancer effects exerted by the lipophilic bioactive compounds in those algae. Interventional human trials have shown that Fx and brown algae mitigate certain risk factors for CRC; however, the direct mechanisms underlying the anti-CRC properties of Fx remain elusive. Fx and its deacetylated type “fucoxanthinol” (FxOH) have been reported to exert potential anticancer effects in preclinical cancer models through the suppression of many cancer-related signal pathways and the tumor microenvironment or alteration of the gut microbiota. We herein review the most recent studies on Fx as a potential candidate drug for CRC prevention.

Apixaban and Dalteparin for the Treatment of Venous Thromboembolism in Patients with Different Sites of Cancer

2021 ◽  
Author(s):  
Giancarlo Agnelli ◽  
Andrés Muñoz ◽  
Laura Franco ◽  
Isabelle Mahé ◽  
Benjamin Brenner ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Gastrointestinal Cancer ◽  
Absolute Risk ◽  
Gynecological Cancer ◽  
Risk Difference ◽  
Efficacy And Safety ◽  
Patients With Cancer ◽  
Genitourinary Cancer ◽  
Spectrum Of Patients

AbstractEfficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.

scholarly journals Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis

2019 ◽  
Vol 21 (4) ◽  
pp. 271-281 ◽  
Author(s):  
Niels C Pedersen ◽  
Michel Perron ◽  
Michael Bannasch ◽  
Elizabeth Montgomery ◽  
Eisuke Murakami ◽  
...  
Keyword(s):  
Heart Disease ◽  
Effective Treatment ◽  
Neurological Disease ◽  
Severe Disease ◽  
Nucleoside Analog ◽  
Efficacy And Safety ◽  
Safety And Efficacy ◽  
Feline Infectious Peritonitis ◽  
Naturally Occurring ◽  
Long Time

Objectives The aim of this study was to determine the safety and efficacy of the nucleoside analog GS-441524 for cats suffering from various forms of naturally acquired feline infectious peritonitis (FIP). Methods Cats ranged from 3.4–73 months of age (mean 13.6 months); 26 had effusive or dry-to-effusive FIP and five had non-effusive disease. Cats with severe neurological and ocular FIP were not recruited. The group was started on GS-441524 at a dosage of 2.0 mg/kg SC q24h for at least 12 weeks and increased when indicated to 4.0 mg/kg SC q24h. Results Four of the 31 cats that presented with severe disease died or were euthanized within 2–5 days and a fifth cat after 26 days. The 26 remaining cats completed the planned 12 weeks or more of treatment. Eighteen of these 26 cats remain healthy at the time of publication (OnlineFirst, February 2019) after one round of treatment, while eight others suffered disease relapses within 3–84 days. Six of the relapses were non-neurological and two neurological. Three of the eight relapsing cats were treated again at the same dosage, while five cats had the dosage increased from 2.0 to 4.0 mg/kg q24h. The five cats treated a second time at the higher dosage, including one with neurological disease, responded well and also remain healthy at the time of publication. However, one of the three cats re-treated at the original lower dosage relapsed with neurological disease and was euthanized, while the two remaining cats responded favorably but relapsed a second time. These two cats were successfully treated a third time at the higher dosage, producing 25 long-time survivors. One of the 25 successfully treated cats was subsequently euthanized due to presumably unrelated heart disease, while 24 remain healthy. Conclusions and relevance GS-441524 was shown to be a safe and effective treatment for FIP. The optimum dosage was found to be 4.0 mg/kg SC q24h for at least 12 weeks.

scholarly journals Anatomy and Imaging of Rat Prostate: Practical Monitoring in Experimental Cancer-Induced Protocols

Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 68
Author(s):  
Mário Ginja ◽  
Maria J. Pires ◽  
José M. Gonzalo-Orden ◽  
Fernanda Seixas ◽  
Miguel Correia-Cardoso ◽  
...  
Keyword(s):  
Imaging Modalities ◽  
Resonance Imaging ◽  
Microscopic Anatomy ◽  
Research Protocols ◽  
Experimental Cancer ◽  
Cancer Models ◽  
The Status ◽  
Prostate Cancer Development ◽  
Magnetic Resonance Imaging Mri ◽  
Rat Prostate

The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).

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