COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Current status of chemotherapy for gastric cancer

High response rates to combination chemotherapy reported by the end of the seventies led many oncologists to recommend standard treatment for gastric cancer. In randomized trials conducted by different groups, the response rate with fluorouracil (F), adriamycin (A), mitomycin C (M) ranged between 17 and 39% and was advocated for adjuvant treatment. However, further studies indicate that combination chemotherapy has no beneficial effect on survival compared with 5-FU alone. Several studies assessing the FAM regimen versus control in the adjuvant setting show, so far, no difference between the treatment arms. Other agents and combinations have recently been investigated. Cisplatin (P) is active in gastric cancer. In six studies using a combination with FA (FAP), the response rate ranged between 29 and 55% with a median survival of 4-12 months. Other combinations using P with F or etoposide and A have also been promising. Recently, the EORTC Gastrointestinal Group, using a combination of sequence of high dose methotrexate and F with A (FAMTX) reported 22 positive responses out of 66 eligible patients, including nine complete responders. These new treatments are currently being tested by different groups in a randomized trial. For the time being, apart from 5-FU alone, chemotherapy in advanced gastric cancer should not be administered on a routine basis outside clinical trials. © 1988.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Adjuvant treatment of colon cancer. A plea for a large-scale European trial

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An EORTC Gastrointestinal (GI) Group randomized evaluation of the toxicity of sequential high dose methotrexate and 5-fluorouracil combined with adriamycin (FAMTX) vs 5-fluorouracil, adriamycin and mitomycin (FAM) in advanced gastric cancer

Until now advanced gastric cancer has been generally treated with the FAM chemotherapy protocol. Due to the relatively low response rates with this protocol we decided to start a randomized prospective phase II trial comparing the FAM with the FAMTX protocol. The primary aim of our trial was to compare the toxicity in both protocols. The FAMTX protocol has been demonstrated to be fully comparable with the toxicity of the FAM protocol. The trial has been extended to a phase III study. With respect to response rates and survival times it is too early for evaluation. © 1989, Humana Press Inc. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase II study of epirubicin in advanced adenocarcinoma of the pancreas

The EORTC Gastrointestinal Group has conducted a phase II trial in 41 patients with locally advanced or metastatic adenocarcinoma of the pancreas with epirubicin 90 mg/m2 intravenously every 4 weeks, with dose escalation if possible. Seven patients were not evaluable for response. In 34 evaluable patients there were two complete and six partial responses (response rate 24%). Nine patients had stable disease for at least 2 months, including one patient with a minor response. Median time to progression for responders was 7 months, for all patients 3 months. Median survival for responders was 9 months, for all patients 5 months. It is concluded that epirubicin is an active drug in pancreatic cancer. © 1985.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An EORTC gastrointestinal group phase II evaluation of epirubicin combined with 5-fluorouracil in advanced adenocarcinoma of the pancreas

The EORTC Gastrointestinal Group has conducted a phase II trial in 47 patients with locally advanced or metastatic adenocarcinoma of the pancreas with epirubicin 90 mg/m2 intravenously on day 1 in combination with 5-fluorouracil 500 mg/m2 in a 2 hr infusion day 1-4, every 4 weeks. Of 43 evaluable patients there were six early deaths due to tumour progression and one due to a cerebrovascular accident. There were six partial responses for a response rate of 14% including early deaths. The median survival for all patients was 4 months. It is concluded that the addition of 5-fluorouracil to epirubicin does not appear to enhance the therapeutic results of epirubicin alone. © 1987.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An EORTC gastrointestinal group phase II evaluation of epirubicin combined with ifosfamide in advanced adenocarcinoma of the pancreas

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Randomized phase II study of a combination of cisplatin (DDP), 5-fluorouracil (5-FU), and allopurinol (HPP) versus 5-FU in advanced colorectal carcinoma. An EORTC gastrointestinal tract cancer cooperative group study

In order to improve the therapeutic index of fluorouracil (5-FU), it has been combined with cisplatin (DDP) as synergistic agent and with allopurinol (HPP) as toxicity modulator. Patients with measurable colorectal carcinoma, previously untreated by chemotherapy, were randomized to receive either 5-FU alone 500 mg/m2 push iv days 1-5 or HPP 3 x 300 mg po, days 1-5, 5-FU 800 mg/m2 push iv, days 3-5 and DDP 50 mg/m2 d6. Treatment was repeated every 4 weeks. Of 104 patients randomized, 82 were evaluable for response and survival. Six partial responses were seen in each treatment group (15%) and the median survival time was 7 months. Hematologic toxicities were comparable in both treatment groups, with a mean nadir white blood cell count of 3500/ vs. 3800/mm3 and a mean nadir platelet count of 148,000/ vs, 203,000/mm3 for HPP-5-FU-DDP and 5-FU, respectively. This study suggests that the addition of both HPP and DDP does not improve the activity of 5-FU.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cis-platinum as second-line chemotherapy in advanced gastric adenocarcinoma. A phase II study of the EORTC gastrointestinal tract cancer cooperative group

Thirty-four patients with measurable metastatic gastric adenocarcinoma refractory to prior chemotherapy were treated with cis-platinum 100 mg/m2 in a 6-hr infusion at 3-week intervals. Thirty-one patients were evaluable for response. There were three complete and three partial responses. Median duration of response was 4 months. Toxicity consisted mainly of nausea and vomiting and was severe in 12 patients. One patient had a severe but reversible renal failure. These results confirm other data reported in the literature. Cis-platinum has activity in gastric adenocarcinoma and should now be further investigated in first-line chemotherapy. © 1985.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Weekly high-dose 5-fluorouracil and folinic acid in metastatic pancreatic carcinoma: a phase II study of the EORTC GastroIntestinal Tract Cancer Cooperative Group.

The aim of the study was to assess the response rate and toxicity of high-dose 24 h infusion of 5-fluorouracil (5FU) in metastatic adenocarcinoma of the pancreas. Patients with measurable disease, performance status 0-2, and no prior chemotherapy were registered to receive cycles of leucovorin (LV) 500 mg/m2 (or l-LV 250 mg/m2 over 1 h followed by 5FU 2.6 g/m2 over 24 h, weekly for 6 weeks, followed by a 2-week rest. The main endpoints were the response rate and toxicity. From 37 patients, 36 were the analysed for toxicity, and 33 were eligible and analysed for response. The median age was 59 years (range 28-74 years), and the median performance status was 1. Partial response was observed in three patients (9%) (95% Confidential Interval (CI): [2-24]%). Main grade 3/4 National Cancer Institute (NCI) common toxicity criteria toxicities (patients) were diarrhoea (n = 3), vomiting (n = 2) and hand-foot syndrome (n = 5). Median time to progression was 7 weeks (95% CI: [6.4-11.7] weeks) and median survival 19 weeks (95% CI: [12-35] weeks). In conclusion, high-dose 5FU and folinic acid is well tolerated, but has only modest activity in pancreatic cancer.Clinical TrialClinical Trial, Phase IIJournal ArticleMulticenter Studyinfo:eu-repo/semantics/publishe