Intravesical therapy with the trifunctional anti-EpCAM/CD3 bsAb Catumaxomab is well tolerated and shows encouraging preliminary efficacy in patients with high-risk NMIBC (CATUNIBLA phase I trial).

e16555 Background: Tx of high-risk NMIBC is challenging due to a high risk of recurrence. Novel therapeutic options are highly anticipated to avoid cystectomy and disease progression. Malignant transitional cells express EpCAM. The trifunctional anti-EpCAM/CD3 bsAb Catumaxomab (CAT) mediates cell killing against human BC. This dose escalating Phase I trial (NCT04819399) investigates the safety of intravesical CAT in high-risk NMIBC. Methods: Following first TUR-B, pts with newly diagnosed high-risk NMIBC were enrolled and received 6 x weekly intravesical CAT instillations, each of 2h duration) at a dose of 50 or 70μg. Subsequently, 2nd TUR-B and adjuvant instillation therapy (tx) was performed as SoC. Here, we report the safety and preliminary efficacy of dose cohorts 1 and 2. Results: 7 Pts are included, 5 with pTa, 2 with pT1 disease. There were 5 concomitant pTis. 6/7 pts received the planned 6 x weekly CAT instillations. 1 pt discontinued after 1 instillation due to recurrent UTI. No DLTs occurred. 28 AEs were observed in 6/7 pts, all of gr 1-2 except two unrelated gr 3 AEs . 2/7 pts had an unrelated SAE each (1 hydronephrosis, 1 recurrent fever after BCG). For 6/7 pts cytokines were below LLQ. In one pt of cohort 2 low amounts of IL-6 and IL-8 were detectable. Weak HAMA responses in 5/6 pts transiently occurred at days 29 and 43. CAT instillations led to transient increases of urinary leukocytes. During and after CAT treatment, there was a strong trend towards reduction of EpCAM+ cells in urine. At 2nd TUR-B tumour persistency was observed in two patients only. Remarkably, 3/5 pTis were no longer detected at 2nd TUR-B. So far, 5/7 pts received adjuvant BCG, 2 pts declined. 7/7 pts achieved CR as best response. While 2/3 pts in the 50 μg cohort had a recurrence, no recurrence was observed in the 70 μg cohort. Conclusions: Intravesical instillations with the trifunctional, anti-EpCAM/anti-CD3 bsAb Catumaxomab are well tolerated in pts with high risk NMIBC. CAT does not enter systemic circulation and elicits only low and transient immunogenicity. The MTD is not reached and dose escalation is still ongoing with cohort 3 (100 μg)(updated results will be presented at meeting). The reduction in EpCAM+ urine cells indicates potential activity of this novel immunotherapy and the high CR rate of Tis at the end of CAT therapy is promising. Clinical trial information: NCT04819399. [Table: see text] </jats:p

Guidelines on the prevention and treatment of venous thromboembolism in cancer patients treated surgically, including patients under 18 years of age

Żylna choroba zakrzepowo-zatorow (ŻChZZ), jest jednym z najgroźniejszych powikłań choroby nowotworowej. Terapia przeciwnowotworowa, zabiegi operacyjne czy znacznego stopnia zaawansowanie choroby nowotworowej to tylko niektóre czynniki ryzyka ŻChZZ, stanowiącej nadal jedną z najczęstszych przyczyn zgonu w populacji pacjentów onkologicznych. Duże ryzyko wystąpienia zakrzepicy żył głębokich (ZŻG) oraz ryzyko różnych powikłań, w tym powikłań krwotocznych, pomiędzy poszczególnymi grupami chorych onkologicznych sugeruje przeprowadzenie indywidualnej oceny ryzyka i postępowanie profilaktyczne zależne od sytuacji klinicznej konkretnego pacjenta. Uzasadnia to także stałą aktualizację wytycznych postępowania profilaktycznego proponowanego chorym onkologicznym, czego dowodem jest niniejszy dokument, będący aktualizacją opublikowanych w 2016 wytycznych. W dokumencie zawarto dane opublikowane po 2016 roku i zawiera on najnowsze wskazania dotyczące postępowania profilaktycznego w populacji chorych onkologicznych, ze szczególnym uwzględnieniem profilaktyki przeciwzakrzepowej w dyscyplinach zabiegowych. Został ponadto poszerzony o wskazania dotyczące pacjentów poniżej 18. roku życia

The effect of GA on proliferation and induction of cell death of OS 143B cells.

<p><b>A</b>. GA inhibits OS 143B cell growth. OS 143B cells were treated for 24 h with serial GA dilutions (within the range of 0.8 µM–50 µM). The cell viability was then determined by means of MTT assay. Data from at least three independent experiments are presented as mean ± SE. The absence of error bar denotes a line thickness greater than the error. Data were analyzed by GraphPad Prism Software version 6.02 performing One-way ANOVA combined with Dunett's Multiple Comparison Test. *P<0.01 vs. control. <b>B–D</b>. GA induced cell death of OS 143B cells. 143B OS cells were treated with 4 µM GA for 24 h, the cells were then harvested and the percentage of apoptotic and necrotic cells was determined performing double PI-Annexin V staining. <b>B</b>. Annexin V, PI-live/dead dot plots showing apoptosis and necrosis before and after treatment with GA. Plots are representative of five individual experiments. <b>C–D</b>. Total apoptotic (C) and necrotic (D) cell number before and after treatment with GA. Data from at least three independent experiments are presented as mean ± SE. Data were analyzed using GraphPad Prism (GraphPad Software, Inc., version 6.02, USA). Significant differences between groups were determined by Student's t-test. *P<0.01, ***P<0.0001 vs. control.</p

GA affected HSPs gene expression in OS 143B cells.

<p>OS 143B cells were treated with GA (4 µM) for 6 h; the levels of Hsp60, Hsp70, Hsp90AA1, Hsp90AB1, Hsp90B1 transcript were then determined by means of Real Time PCR. Treatment with GA resulted in upregulation of Hsp60 (A), Hsp70 (B), Hsp90AA1 (C), Hsp90AB1 (D) transcript, however it did not impact Hsp90B1 gene expression (E). Values are mean ± SE of three independent experiments, relative mRNA levels of HSP/beta-actin are presented. The data were analyzed by Student's t-test using GraphPad Prism Software version 6.02. *P<0.01, **P<0.001 vs. control.</p

Usefulness of Somatostatin Receptor Scintigraphy (&lt;sup&gt;99m&lt;/sup&gt;Tc-[HYNIC, Tyr3]-Octreotide) and &lt;sup&gt;123&lt;/sup&gt;I-Metaiodobenzylguanidine Scintigraphy in Patients with &lt;b&gt;&lt;i&gt;SDHx&lt;/i&gt;&lt;/b&gt; Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography

&lt;b&gt;&lt;i&gt;Aims:&lt;/i&gt;&lt;/b&gt; The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using &lt;sup&gt;99m&lt;/sup&gt;Tc-[HYNIC, Tyr3]-octreotide (TOC) and &lt;sup&gt;123&lt;/sup&gt;I-metaiodobenzylguanidine (mIBG) in patients with &lt;i&gt;SDHx&lt;/i&gt;-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in &lt;i&gt;SDHx&lt;/i&gt; mutation carriers. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and &lt;sup&gt;123&lt;/sup&gt;I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; We evaluated 46 &lt;i&gt;SDHx&lt;/i&gt; gene mutation carriers (32 index cases and 14 relatives; 28 &lt;i&gt;SDHD&lt;/i&gt;, 16 &lt;i&gt;SDHB&lt;/i&gt; and 2 &lt;i&gt;SDHC&lt;/i&gt;). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of &lt;sup&gt;123&lt;/sup&gt;I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p &lt; 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest &lt;sup&gt;123&lt;/sup&gt;I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; SRS and &lt;sup&gt;123&lt;/sup&gt;I-mIBG single photon emission computed tomography (SPECT) sensitivity in &lt;i&gt;SDHx&lt;/i&gt; patients is highly body region dependent. In malignant tumors, SRS is superior to &lt;sup&gt;123&lt;/sup&gt;I-mIBG SPECT.</jats:p