Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Long-Term Results of a Prospective Phase II Study.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.

Erdafitinib treatment in metastatic urothelial carcinoma: a real-world analysis.

Background: Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It was approved based on a phase 2 clinical trial, revealing a 40% response rate, and 13.8 months overall survival. These FGFR genomic alterations are uncommon. Thus, real-world data on erdafitinb use is scant. We herein describe erdafitinib treatment outcome in a real world patient cohort. Methods: We retrospectively reviewed the data of patients treated with erdafitinib from 9 Israeli medical centers. Results: Twenty-five patients with metastatic urothelial carcinoma (median age 73, 64% male, 80% with visceral metastases) were treated with erdafitinib between January 2020 to October 2022. A clinical benefit (complete response 12%, partial response 32%, stable disease 12%) was seen in 56%. Median progression-free survival was 2.7 months, and median overall survival 6.73 months. Treatment related toxicity ≥ grade 3 occurred in 52%, and 32% discontinued therapy due to adverse events. Conclusions: Erdafitinib therapy is associated with a clinical benefit in the real world setting, and associated with similar toxicity as reported in prospective clinical trials.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study.

Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.

Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: Limited data about biomarkers are available to predict the outcomes of targeted therapy in metastatic renal cell carcinoma (mRCC). Circulating cell-free DNA (CFD) is elevated in various cancers. PATIENTS AND METHODS: We performed a prospective study of patients with mRCC who received targeted therapy in the Soroka Medical Center between 2013 and 2015. CFD levels were measured using a simple fluorometric assay. Blood samples for CFD were collected before treatment and at weeks 1, 4, 12, 18, and 24 of treatment. The normal cut-off level of CFD was defined as 800 ng/ml. The association of CFD with objective response, progression-free survival (PFS), and overall survival was tested, with adjustment for known confounding risk factors. RESULTS: A total of 23 patients were included; 18 were treated with first-line therapy and 5 with second- and third-line therapies. Patients with normal pretreatment CFD level had a better PFS versus patients with increased levels (p = 0.023). In multivariate analysis, factors associated with PFS were pretreatment CFD levels (p = 0.020) and Heng risk (p = 0.006). CONCLUSIONS: Elevated pretreatment CFD levels measured using a simple fluorometric assay may be associated with a worse PFS in patients with mRCC. A larger prospective study is warranted in order to validate our observation.

The Association between Age-Related Macular Degeneration and Renal Cell Carcinoma: A Nested Case-Control Study.

Background: Overexpression of VEGF is implicated in the pathogenesis of both renal cell carcinoma (RCC) and age-related macular degeneration (AMD). We evaluated the association between AMD and RCC risk.Methods: We conducted a matched case-control study within a population-representative database from the United Kingdom. Study cases were defined as individuals with any diagnostic code of RCC. For every case, four eligible controls were matched on age, sex, practice site, calendar time, and duration of follow-up. Exposure of interest was diagnosis of AMD prior to cancer diagnosis. Adjusted ORs and 95% confidence intervals (CI) for RCC were estimated using conditional logistic regression. In a secondary analysis, we evaluated the association between other retinopathies and RCC and AMD and the hypovascular pancreatic cancer.Results: The study population included 1,547 patients with RCC and 6,066 matched controls. Median follow-up time was 6 years (IQR, 3-9). AMD diagnosis was associated with a significantly increased RCC risk (OR, 1.89; 95% CI, 1.09-3.29). In contrast, there was no association between other retinopathies and RCC risk (OR, 0.8; 95% CI, 0.56-1.15). AMD was associated with a lower risk for pancreatic cancer (OR, 0.47; 95% CI, 0.35-0.64).Conclusions: Patients with AMD may be at higher risk for RCC. Providers should be aware of this potential link and consider screening for RCC within this population.Impact: Providers should be aware of the potential link between AMD and RCC. Cancer Epidemiol Biomarkers Prev; 26(5); 743-7. ©2017 AACR.

Male factor infertility, low fertilisation rate following ICSI and low number of high-quality embryos are associated with high order recurrent implantation failure in young IVF patients.

BACKGROUND: The aim of this study was to characterise the clinical and laboratory parameters in young in vitro fertilisation(IVF) patients with high order recurrent implantation failure (RIF). METHODS: The first 3 cycles (n = 141 cycles) of 47 consecutive (age <35 years) couples with RIF (> or =6 IVF cycles) were compared with 252 consecutive cycles of 152 couples,treated during the same period, who conceived within the first 3 IVF cycles. RESULTS: The incidence of male factor infertility or of combined male and female factors was significantly higher in the study group than the control group (male factor: 78.7 versus 42.5%, p= 0.002, OR = 3.2 (95% CI: 1.56.8)). Lower fertilisation rates were noted for the intracytoplasmic sperm injection (ICSI)-treated oocytes of the study group compared with the control group. The availability of high quality embryos for transfer was significantly lower in the RIF group. On multivariate logistic regression analysis, the significantly different variables between the groups were cause of infertility (male factor or combined male and female factors) (p = 0.03),fertilisation rate (p = 0.038), and semen concentration (p = 0.05). CONCLUSIONS; Young IVF patients with high order RIF are characterised by male factor infertility, lower fertilisation rate with ICSI, and fewer high quality embryos available for transfer.