Trends in Use and Perceptions About Triplet Chemotherapy Plus Bevacizumab for Metastatic Colorectal Cancer.

Importance: Triplet chemotherapy with fluorouracil, folinic acid, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-B) is an effective first-line treatment option for patients with metastatic colorectal cancer (mCRC). However, the degree of implementation of FOLFOXIRI-B in daily practice is unknown. Objectives: To evaluate the current adoption rate of FOLFOXIRI-B in patients with mCRC and investigate the perspectives of medical oncologists toward this treatment option. Design, Setting, and Participants: This 1-week, multicenter, cross-sectional study in the Netherlands used a flash mob design, which facilitates ultrafast data generation (flash) through the engagement of numerous researchers (mob). During the study week (March 1-5, 2021), patient data were retrieved from electronic health records of 47 hospitals on patients with mCRC who were referred to a medical oncologist between November 1, 2020, and January 31, 2021. Interviews were simultaneously conducted with 101 medical oncologists from 52 hospitals who regularly treat patients with mCRC. Exposure: First-line systemic treatment as determined by the treating physician. Main Outcomes and Measures: The FOLFOXIRI-B prescription rate was the main outcome. Current practice was compared with prescription rates in 2015 to 2018. Eligibility for treatment with FOLFOXIRI-B was estimated. An exploratory outcome was medical oncologists' reported perspectives on FOLFOXIRI-B. Results: A total of 5948 patients in the Netherlands (median age [interquartile range], 66 [57-73] years; 3503 [59%] male; and 3712 [62%] with left-sided or rectal tumor) were treated with first-line systemic therapy for synchronous mCRC. A total of 282 patients with mCRC underwent systemic therapy during the study period (2021). Of these 282 patients, 199 (71%) were treated with intensive first-line therapy other than FOLFOXIRI-B, of whom 184 (65%) were treated with oxaliplatin doublets with or without bevacizumab; 14 (5%) with irinotecan doublets with or without bevacizumab, panitumumab, or cetuximab; and 1 (0.4%) with irinotecan with bevacizumab. Fifty-four patients (19%) were treated with fluoropyrimidine monotherapy with or without bevacizumab, 1 patient (0.4%) with panitumumab monotherapy, and 3 (1%) with immune checkpoint inhibitors. In total, 25 patients (9%; 95% CI, 6%-12%) were treated with first-line FOLFOXIRI-B compared with 142 (2%; 95% CI, 2%-3%) in 2015 to 2018. During the study period, 21 of 157 eligible patients (13.4%) in the Netherlands were treated with FOLFOXIRI-B. A total of 87 medical oncologists (86%) reported discussing FOLFOXIRI-B as a treatment option with eligible patients. A total of 47 of 85 (55%) generally communicated a preference for a chemotherapy doublet to patients. These oncologists reported a significantly lower awareness of guidelines and trial results. Toxic effects were the most reported reason to prefer an alternative regimen. Conclusions and Relevance: The findings of this study suggest that FOLFOXIRI-B prescription rates have marginally increased in the last 5 years. Considering that most medical oncologists discuss this treatment option, the prescription rate found in this study was below expectations. Awareness of guidelines and trial data seems to contribute to the discussion of available treatment options by medical oncologists, and the findings of this study suggest a need for repeated and continuing medical education.

NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. PATIENTS AND METHODS: This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). RESULTS: During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.

5-Fluorouracil in combination with deoxyribonucleosides and deoxyribose as possible therapeutic options for the Coronavirus, COVID-19 infection.

The recent global pandemic created by the Coronavirus SARS-CoV-2, started in Wuhan, China in December 2019, has generated panic, both in term of human death (4-5% of infected patients identified through testing) and the global economy. Human sufferings seem to be continuing, and it is not clear how long this will continue and how much more destruction it is going to cause until complete control is achieved. One of the most disturbing issues is Covid-19 treatment; although a large number of medications, previously used successfully with other viruses (including Chinese herbal medicines and anti-malaria drugs), are under consideration, there remain questions as to whether they can play a satisfactory role for this disease. Global attempts are ongoing to find the drugs for the treatment of this virus but none of the antiviral drugs used for treatment of other human viral infection is working and hence attempts to find new drugs are continuing. Here the author is proposing that 5-Fluorouracil (5-FU) which when used on its own is failing as an antiviral agent due to the removal of this compound by proof reading ability exceptionally found in Coronaviruses. The author here is proposing to test 5-FU in combination with a number of deoxynucleosides on animal models infected with this Covid-19. Should encouraging results ensue, therapies could then be tried on patients.