Randomized double-blind, placebo-controlled multicenter phase III study of prevention of irinotecan-induced diarrhea by a probiotic mixture containing Bifidobacterium BB-12®Lactobacillus rhamnosus LGG® in colorectal cancer patients.

Background: The incidence of irinotecan-induced diarrhea varies between 60-90%, by which the incidence of severe diarrhea is 20-40%. The objective of this phase III trial was to determine the effectiveness of the probiotic mixture containing Bifidobacterium, BB-12® and Lactobacillus rhamnosus, LGG® in the prophylaxis of irinotecan-induced diarrhea in metastatic colorectal cancer patients due to a reduction in the activity of intestinal beta-D-glucuronidase. Methods: From March 2016 to May 2022, a total of 242 patients with colorectal cancer starting a new line of irinotecan-based therapy were registered to the study in 11 cancer centers in Slovakia. Patients were randomized in a ratio 1:1 to probiotic formula vs. placebo that was administered for 6 weeks. Each capsule of Probio-Tec® BG-Vcap-6.5 contained 2.7x109 colony-forming units (CFU) of 2 lyophilized probiotic strains Bifidobacterium, BB-12® (50%) and Lactobacillus rhamnosus GG, LGG® (50%). Results: Administration of probiotics compared to placebo was not associated with a significant reduction of grade 3/4 diarrhea (placebo arm 11.8% vs. probiotic arm 7.9%, p=0.38). Neither the overall incidence of diarrhea (46.2% vs. 41.2%, p=0.51) nor the incidence of enterocolitis (3.4% vs. 0.9%, p=0.37) was different in the placebo vs. probiotic arm. Subgroup analysis revealed that patients with colostomy had higher incidence of any diarrhea and grade 3/4 diarrhea in the placebo arm compared to the probiotic arm (48.5% vs. 22.2%, p=0.06 and 15.2% vs. 0%, p=0.06, respectively). Moreover, patients on probiotic arm had significantly better diarrhea-free survival (HR = 0.41, 95%CI 0.18 - 0.95, p=0.05) and needed less loperamide (p=0.01) compared to patients on placebo arm. We did not observe any infection caused by probiotic strains used in this study. Conclusion: This study failed to achieve its primary endpoint, and results suggest a lack of benefit of administered probiotic formula for the prevention of irinotecan-induced diarrhea. However, subgroup analysis suggests a possible benefit in patients with colostomy.

COVID-19 and oncological disease.

BACKGROUND: Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus named SARS-CoV-2, initially emerged in China in late 2019. The rapid global spread of this novel virus led the World Health Organization declare a pandemic with > 30,000,000 confirmed cases, 946,000 deaths and > 21,000,000 recoveries reported as of 18 September 2020, according to the Johns Hopkins Coronavirus Resource Center. Initial reports from Asia suggested that elderly patients with multiple comorbidities, specifically diabetes, hypertension, and obesity were at an increased risk of developing severe COVID-19 following a SARS-CoV-2 infection. As data on these risks have evolved, evidence has increasingly shown that patients with cancer are indeed a particularly vulnerable group. However, the effects of various confounding factors, including an older than average patient population who often have underlying comorbidities including a suppressed immune system and/ or a hypercoagulable state, have been difficult to separate from the effects of having cancer. Common presenting symptoms of SARS-CoV-2 including dyspnoea, cough, fever, fatigue, dysgeusia and, less commonly, diarrhoea and/ or a hyperinflammatory syndrome are equally confusing to clinicians as they all are common symptoms of both cancer and toxicity from anti-cancer therapy. Furthermore, the radiographic dilemma of distinguishing between immune-checkpoint inhibitor-induced pneumonitis from that caused by SARS-CoV-2 infection and conflicting data on the effects of certain therapies on patient outcomes has left clinicians with considerable angst on how to help patients with acute or worsening symptoms in an optimal way. Predicted increase in mortality follows not only from the delay in discovery and progress resulting from temporary closing of research laboratories at cancer centers but also from diversion of resources to patient care and temporary suspension of clinical trial enrolment both by companies and local institutions. The possibilities of travelling to specialized medical centers whose activities are essential for the delivery and improvement of patient care were reduced, too. Viral mutations might also occur during transmission and spread; this leads to a statement that SARS-CoV-2 will forever remain a looming threat to the oncological community. What is crucial to remember is that cancer itself is a pandemic with > 18,000,000 people dia-gnosed worldwide every year. Many societies, including the European Society for Medical Oncology and the American Society of Clinical Oncology, are providing clinical recommendations for the management of patients with cancer during this challenging time, recognizing that continuation in the precise treatment of our patients is critical for our role of physicians. PURPOSE: The aim of the presentation is to point out the contact or overlapping areas of both mentioned disease entities for the purpose of possible simplification of dia-gnostic and therapeutic management of a cancer patient with suspected or already proven  COVID-19 disease.

The first cancer patient with COVID-19 in Slovakia.

BACKGROUND: In December 2019 a new strain of coronavirus SARS-CoV-2 has emerged and affected health care worldwide. Patients with cancer and other comorbidities are at increased risk for adverse outcomes in this infection. CASE: In this case report we present a 75-year-old patient with a localized gastric adenocarcinoma, currently treated by perioperative chemotherapy regimen, who had an rT-PCR proven novel coronavirus SARS-CoV-2 infection. Laboratory and radiologic assessments were performed in order to assess disease severity; however, the findings were not altered in accordance with the findings associated with COVID-19 disease. RESULTS: On the first hospital day the patient had a low grade fever with chills. Subsequently a pharmacological therapy with hydroxychloroquine and azithromycin was started. After pharmacologic and symptomatic treatment, the patient was reassessed for SARS-CoV-2, with negative results. At discharge, the patient was ordered a 14-day mandatory quarantine. After 57 days of follow-up, the patient underwent a new rapid antibody test by Acro Biotech inc., which gave negative results for IgM and IgG. CONCLUSION: An infection with SARS-CoV-2 is associated with a more severe disease in patients with comorbidities and cancer; however, this case patient had a mild course of COVID-19 disease. The aim of this case report is to share the information on the clinical course and outcomes of a patient with malignancy. Rapid spreading of information is crucial in the management of COVID-19.

Intrathecal administration of trastuzumab with cytarabine and methotrexate in breast cancer patients with leptomeningeal carcinomatosis.

HER2-positive status is associated with increased risk of central nervous system (CNS) metastases in breast cancer patients. Leptomeningeal carcinomatosis (LMC) represents a rare but disastrous manifestation of metastatic breast cancer (MBC) with limited treatment options and poor prognosis. Several case reports of intrathecal (i.t.) trastuzumab in the treatment of LCM were published so far. Usually, i.t. trastuzumab was administered in monotherapy or in combination with metothrexate. Herein, we report for the first time two patients with metastatic breast cancer and leptomeningeal carcinomatosis treated by intrathecal methotrexate (15 mg total dose) and cytarabine (24 mg total dose) with escalating dose of trastuzumab. We observed that up to 100 mg of trastuzumab can be safely administered intratecally with i.t. metothrexate and cytarabine. Both patients achieved good control of leptomeningeal disease for 13.5 and 6 months without significant toxicity. We suggest that i.t. trastuzumab with cytarabine and metothrexate is associated with promising benefit and warrant further investigation.