Multicentre, interventional, single-arm study protocol of telemonitored circadian rhythms and patient-reported outcomes for improving mFOLFIRINOX safety in patients with pancreatic cancer (MultiDom, NCT04263948).

INTRODUCTION: Circadian clocks regulate cellular proliferation and drug effects. Tolerability and/or efficacy of anticancer therapies have been improved by their administration according to circadian rhythms, while being predicted by circadian robustness. The combination of leucovorin, fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) is a standard treatment for pancreatic ductal adenocarcinoma (PDAC), that generates grades 3-4 adverse events in the majority of patients and an estimated 15%-30% emergency admission rate. The MultiDom study evaluates whether mFOLFIRINOX safety can be improved using a novel circadian-based telemonitoring-telecare platform in patients at home. The detection of early warning signals of clinical toxicities could guide their early management, possibly preventing emergency hospital admissions. METHODS AND ANALYSIS: This multicentre, interventional, prospective, longitudinal, single-arm study hypothesises that the mFOLFIRINOX-related emergency admission rate will be 5% (95% CI 1.7% to 13.7%), among 67 patients with advanced PDAC. Study participation is 7 weeks for each patient, including a reference week before chemotherapy onset and 6 weeks afterwards. Accelerometry and body temperature are measured q1-min using a continuously worn telecommunicating chest surface sensor, daily body weight is self-measured with a telecommunicating balance and 23 electronic patient-reported outcomes (e-PROs) are self-rated using a tablet. Hidden Markov model, spectral analyses and other algorithms automatically compute physical activity, sleep, temperature, body weight change, e-PRO severity and 12 circadian sleep/activity parameters, including the dichotomy index I

Progressive erythrocytosis under lenvatinib treatment in patients with advanced hepatocellular carcinoma.

PURPOSE: This manuscript reports on the occurrence of early and frequent erythrocytosis in advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib. METHODS: A cohort of 23 patients with advanced HCC, treated with this antiangiogenic drug for at least one month, was retrospectively analyzed. RESULTS: These patients (82.7% men, median age 58.3, cirrhosis in 60.8%) were treated between October 2019 and September 2020 with lenvatinib, as first-line systemic therapy for 82.6% of them. For 20 patients (87%), an early and significant increase in hemoglobin (Hb) level, up to 1.41 g/dL (p < 0.001) was reported and remained elevated. Ten patients (43.5%), all men, reached erythrocytosis (Hb > 16.5 g/dL), 7 were treated with low-dose aspirin for primary thromboprophylaxis and 2 needed phlebotomy. None underwent thromboembolic complications. A significant Hb decrease was observed after treatment discontinuation (p < 0.05). Erythropoietin (EPO) serum levels also increased, which was attributed to HCC after immunostaining for EPO in liver biopsies. The Naranjo adverse drug reaction probability scale documented the relationship between erythrocytosis and lenvatinib and regression at treatment discontinuation. Erythrocytosis was hypothesized to be a class effect of anti-VEGF therapies, the magnitude of which might depend on the IC50 value of each molecule. CONCLUSION: This report documents the frequent occurrence of erythrocytosis during lenvatinib treatment for advanced HCC, likely secondary to EPO secretion by tumor cells through the antiangiogenic activity levatinib. An early and close monitoring of hematologic parameters is, thus, recommended, together with thromboprophylaxis by low-dose aspirin and phlebotomy in case of symptomatic erythrocytosis.