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Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients.Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm.Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: pop-ulation for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 pa-tients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C.Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher nu-merical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924.(C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

A re-assessment of spionid specimens collected from coasts around the Iberian Peninsula and initially assigned to Dispio uncinata Hartman, 1951 and Prionospio multibranchiata Berkeley, 1927 resulted in the recognition of two new species from the genera Dispio and Prionospio : Dispio glandulosa sp. nov . and Prionospio ( Minuspio ) sanmartini sp. nov . In addition, the examination of specimens collected near the type locality of P. multibranchiata led to a re-description of this species. The specimens examined do not correspond to the material collected from the Iberian Peninsula and it is unlikely that P. multibranchiata is found in northern European waters.

A new solitary species of Loxosomatidae (Entoprocta), Loxosoma discoides n. sp., is described. The specimens were found in the intertidal level of two locations in the Galician (NW Spain) coast. This new species, with “table-tennis bat” appearance, is characterised by showing large lateral wings in the calyx, which confer the singular aspect. It is the first record of this genus at the coast of the Iberian Peninsula.

Re-assessment of spionid specimens from Iberian Peninsula initially assigned to Dispio uncinata Hartman, 1951 and Streblospio benedicti Webster, 1879 led to the recognition of two new species from the spionid genera Dispio and Streblospio from coasts around the Iberian Peninsula. Dispio elegans sp. nov. is characterised by having an oblanceolate-shaped prostomium. In addition, the first two notopodial postchaetal lamellae are serrated with digitiform papillae, the anterior neuropodial lamellae are smooth; all branchiae are almost completely fused to the notopodial lamellae, but with the tips free; the notochaetae on chaetiger 1 are smooth, alimbate capillaries; the ventral chaetae located in the position of the sabre chaetae on chaetigers 1–2 are smooth, alimbate capillaries, but becoming granulated on chaetiger 3; and the middle and posterior chaetigers are granulated and reticulated. Streblospio padventralis sp. nov. is characterized by lacking dorsal papillae between the branchiae of chaetiger 1; the hooks have 4–5 pairs of small teeth; sabre chaetae are present from chaetiger 3; the pygidium has two ventral lappets; and brooding structures are present in the coelomic cavities. We suggest raising the status of Streblospio benedicti japonica Imajima, 1990 to full species level as S. japonica Imajima, 1990. A key for Streblospio species is provided.

The precise determination of dose-effect curves and the combination effect of drugs is of crucial importance in the development of new therapies for the most dreadful diseases. We have found that the current implementations of the theory of Chou et al. are not accurate enough in some circumstances and might lead to erroneous predictions of synergistic or antagonistic behaviour. We have identified the source of inaccuracies and fixed it thereby improving the accuracy of those methods. Here we explain the main features of our approach and demonstrate its higher accuracy as compared to the standard methods. Therefore, this new implementation might have a huge impact in the reliability of future research on new Combination Therapies., This work was supported by FICYT (grant GRUPIN14-121) and by the Spanish MINECO (project FIS2013-45469).